Updated on 2025/07/31

写真a

 
SAITO Rie
 
Organization
Brain Research Institute Center for Bioresources Assistant Professor
Title
Assistant Professor
External link

Degree

  • Doctor (Neuropathology) ( 2018.3   Niigata University )

Research Interests

  • 脳血管障害

  • Neuropathology

  • Neurodegenerative disease

  • 血管性認知症

  • 白質脳症

  • 脊髄小脳変性症

Research Areas

  • Life Science / Anatomy and histopathology of nervous system

  • Life Science / Neurology

Research History (researchmap)

  • Niigata University   Brain Research Institute   Assistant Professor

    2018.4

      More details

  • Niigata University   Graduate School of Medical and Dental Sciences

    2014.4 - 2018.3

      More details

  • 国家公務員共済組合連合会虎の門病院   神経内科   医員

    2012.4 - 2014.3

      More details

  • 国家公務員共済組合連合会虎の門病院   内科   後期専門研修(神経内科専攻)

    2009.4 - 2012.3

      More details

  • 国家公務員共済組合連合会虎の門病院   内科   初期研修

    2007.4 - 2009.3

      More details

Research History

  • Niigata University   Center for Bioresources, Brain Research Institute   Assistant Professor

    2023.4

  • Niigata University   Brain Research Institute   Assistant Professor

    2018.4 - 2023.3

Education

  • Niigata University   Faculty of Medicine   School of Medicine

    2007.3

      More details

Professional Memberships

Committee Memberships

  • The Japanese Society of Neuropathology   Councilor of the International Congress of Neuropathology  

    2024.4   

      More details

  • 日本神経病理学会   将来計画委員/用語委員/基礎臨床連携促進委員会  

    2021.4   

      More details

  • 日本神経病理学会   代議員  

    2018.10   

      More details

    Committee type:Academic society

    researchmap

Qualification acquired

  • 神経内科専門医

 

Papers

  • Mosaic variants of neurodevelopmental and mitochondrial genes in postmortem paraventricular thalamus in bipolar disorder detected by deep exome sequencing

    Masaki Nishioka, Zen‐ichi Tanei, Yuko Saito, Maho Morishima, Mizuki Hino, Kanako Mori, Atsuko Nagaoka, Risa Shishido, Rie Saito, Hideaki Kitamura, Akito Nagakura, Araki Kimura, Shuji Iritani, Kenichi Oshima, Akiyoshi Kakita, Yasuto Kunii, Shigeo Murayama, Tadafumi Kato

    Psychiatry and Clinical Neurosciences   2025.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    <jats:sec><jats:title>Aim</jats:title><jats:p>The genetic architecture of bipolar disorder (BD) remains incompletely understood despite extensive genomic studies. Postzygotic mosaic variants have emerged as promising contributors to BD; however, the landscape of such variants in the BD brain has yet to be elucidated.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed mosaic variants in the paraventricular thalamic region (PVR) from 18 Japanese BD cases and 11 controls using deep whole‐exome sequencing. Candidate variants were validated <jats:italic>via</jats:italic> targeted amplicon sequencing. To explore their biological implications, we performed gene ontology analysis by integrating the brain‐derived mosaic variants identified in this study with mosaic variants previously detected in peripheral tissues.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified 99 exonic and 13 mitochondrial heteroplasmic variants in the PVR. There was a significant enrichment of deleterious mosaic variants in constrained genes (<jats:italic>P</jats:italic> = 0.0402) and of non‐synonymous mosaic variants in neurodevelopmental genes, particularly those involved in the positive regulation of neuron projection development (false discovery rate = 2.32 × 10<jats:sup>−3</jats:sup>). These genes also formed a significantly enriched protein–protein interaction network (<jats:italic>P</jats:italic> = 0.0106). Notably, we detected one mitochondrial variant known to be pathogenic for mitochondrial disease and two predicted pathogenic mitochondrial tRNA variants in BD cases, but none in controls.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Despite the modest sample size and potential confounding factors such as age and cancer status, our direct analysis of brain tissue supports previous findings of an enrichment of mosaic variants in neurodevelopmental and mitochondrial tRNA genes. These results advance our understanding of the genetic underpinnings of BD.</jats:p></jats:sec>

    DOI: 10.1111/pcn.13871

    researchmap

  • Rapidly progressive scalp and lung metastases with fatal pneumothorax in glioblastoma, IDH-wildtype, with MET and CDK6 amplifications: a case report of clinical course and postmortem autopsy, including genetic analysis

    Yoshihiro Tsukamoto, Manabu Natsumeda, Hiroshi Shimizu, Haruhiko Takahashi, Satoshi Shibuma, Asuka Ueno, Akihiro Takahashi, Kazuki Shida, Taiki Saito, Hidemoto Fujiwara, Yoko Nakayama, Yuki Takahashi, Rie Kondo, Rie Saito, Takeyoshi Eda, Masayasu Okada, Kouichirou Okamoto, Toshiaki Kikuchi, Akiyoshi Kakita, Makoto Oishi

    Brain Tumor Pathology   2025.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s10014-025-00503-5

    researchmap

  • Late‐onset multiple system atrophy: Neuropathological features associated with slow disease progression Reviewed

    Misato Ozawa, Rie Saito, Takuya Konno, Yasuko Kuroha, Tetsuhiko Ikeda, Akio Yokoseki, Takashi Tani, Tomoe Sato, Jiro Idezuka, Reiji Koide, Shigeru Fujimoto, Osamu Onodera, Mari Tada, Akiyoshi Kakita

    Brain Pathology   2025.5

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    <jats:title>Abstract</jats:title><jats:p>Patients with late‐onset (LO) multiple system atrophy (MSA), whose initial symptoms appear at age 75 years or older, are more common than previously assumed, but their clinicopathological characteristics remain unclear. We aimed to clarify the clinicopathological features of LO‐MSA. Of 102 patients with autopsy‐confirmed MSA, 5 were identified as having LO‐MSA and 24 as having usual‐age‐onset MSA (UO‐MSA) with a similar disease duration. On the basis of previous reports, we defined UO‐MSA as the appearance of initial symptoms between the ages of 55 and 65 years. We compared the clinical pictures of the two groups and assessed their histopathological features using quantitative and semi‐quantitative methods. The investigated features included the severity of degeneration in the striatonigral (StrN) and olivopontocerebellar (OPC) systems, the numbers of neurons in the brainstem autonomic and spinal intermediolateral nuclei, and the density of α‐synuclein‐immunopositive inclusions in the putamen, inferior olivary nucleus, and ventrolateral medulla (VLM). Most patients with both LO‐MSA and UO‐MSA exhibited the MSA‐olivopontocerebellar atrophy (OPCA) subtype (3/5 and 18/24, respectively). The median disease duration for LO‐MSA patients was 5.5 years, which was comparable to that for patients in our cohort who had developed symptoms below 75 years of age. Pathologically, degeneration of the StrN and OPC systems in LO‐MSA was less severe than that observed in UO‐MSA. Quantitative analysis revealed better preservation of neuron numbers in the brainstem autonomic nuclei in LO‐MSA than in UO‐MSA, with a significantly higher number of serotonergic neurons in the VLM (<jats:italic>p</jats:italic> = 0.013). The density of α‐synuclein‐positive inclusions in the putamen was significantly lower in LO‐MSA than in UO‐MSA (<jats:italic>p</jats:italic> &lt; 0.001). Neuronal degeneration in LO‐MSA may progress more slowly than in UO‐MSA. Accordingly, the prognosis of LO‐MSA may not necessarily be less favorable than that of MSA generally, especially with appropriate care.</jats:p>

    DOI: 10.1111/bpa.70016

    researchmap

  • “Chocolate Chip Sign” on Susceptibility-Weighted Imaging

    Shoichiro Ando, Rie Saito, Sho Kitahara, Masahiro Uemura, Yuya Hatano, Masaki Watanabe, Taisuke Kato, Yosuke Ito, Atchayaram Nalini, Tomohiko Ishihara, Shigeo Murayama, Hironaka Igarashi, Akiyoshi Kakita, Osamu Onodera

    Neurology Genetics   2025.4

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.1212/NXG.0000000000200237

    researchmap

  • Primary spinal cord gliomas: Pathologic features associated with prognosis. Reviewed International journal

    Yuki Tanaka, Manabu Natsumeda, Masayuki Ohashi, Rie Saito, Nayuta Higa, Toshiaki Akahane, Hideki Hashidate, Junko Ito, Satoshi Fujii, Atsushi Sasaki, Akihide Tanimoto, Ryosuke Hanaya, Kei Watanabe, Makoto Oishi, Hiroyuki Kawashima, Akiyoshi Kakita

    Journal of neuropathology and experimental neurology   2024.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Primary spinal cord gliomas are rare and are associated with high mortality. Unlike brain tumors, the clinicopathological features of spinal cord gliomas are not well defined. We analyzed clinical, histopathology, and immunohistochemical features and overall survival (OS) of 25 patients with primary spinal cord gliomas treated between 1994 and 2023 at 4 institutions. IDH1 R132H, H3K27M, and p53 were assessed by immunohistochemistry (IHC). Four (16%), 5 (20%), 2 (8%), and 13 (52%) patients were diagnosed as having grades 1, 2, 3, and 4 gliomas according to the World Health Organization (WHO) 2021 classification, respectively. One case (4%), with a circumscribed diffuse midline glioma, H3K27-altered, had a rare molecular profile and could not be graded. IHC demonstrated H3K27M positivity, indicative of H3F3A K27M or HIST1H3B K27M mutation, in 9 (36%) patients. H3K27me3-loss was evident in 13 (52%) patients. In one patient with a grade 1 tumor that showed negative staining for H3K27M and H3K27me3 loss, numbers of EZHIP-positive cells were increased, suggesting diffuse midline glioma, H3K27-altered (WHO grade 4). H3K27me3 loss, frequency of p53 positive cells (≥10%), MIB-1 index (≥10%), and high histopathological grades significantly correlated with poor OS. These results indicate the pathological and immunohistochemical characteristics of primary spinal cord gliomas that impact prognosis.

    DOI: 10.1093/jnen/nlae084

    PubMed

    researchmap

  • Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans Reviewed

    Samuel D. Chauvin, Shoichiro Ando, Joe A. Holley, Atsushi Sugie, Fang R. Zhao, Subhajit Poddar, Rei Kato, Cathrine A. Miner, Yohei Nitta, Siddharth R. Krishnamurthy, Rie Saito, Yue Ning, Yuya Hatano, Sho Kitahara, Shin Koide, W. Alexander Stinson, Jiayuan Fu, Nehalee Surve, Lindsay Kumble, Wei Qian, Oleksiy Polishchuk, Prabhakar S. Andhey, Cindy Chiang, Guanqun Liu, Ludovic Colombeau, Raphaël Rodriguez, Nicolas Manel, Akiyoshi Kakita, Maxim N. Artyomov, David C. Schultz, P. Toby Coates, Elisha D. O. Roberson, Yasmine Belkaid, Roger A. Greenberg, Sara Cherry, Michaela U. Gack, Tristan Hardy, Osamu Onodera, Taisuke Kato, Jonathan J. Miner

    Nature Communications   15 ( 1 )   2024.6

     More details

    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3′−5′ DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.

    DOI: 10.1038/s41467-024-49066-7

    researchmap

    Other Link: https://www.nature.com/articles/s41467-024-49066-7

  • Clinicopathologic features of two unrelated autopsied patients with Charcot-Marie-Tooth disease carrying MFN2 gene mutation Reviewed

    Hideki Hayashi, Rie Saito, Hidetomo Tanaka, Norikazu Hara, Shin Koide, Yosuke Yonemochi, Tetsuo Ozawa, Mariko Hokari, Yasuko Toyoshima, Akinori Miyashita, Osamu Onodera, Kouichirou Okamoto, Takeshi Ikeuchi, Takashi Nakajima, Akiyoshi Kakita

    Acta Neuropathologica Communications   2023.12

     More details

    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s40478-023-01692-w

    researchmap

  • Marked laterality of olivopontocerebellar pathology in an autopsied patient with MSA: Implications for degeneration and α-synuclein propagation. Reviewed International journal

    Misato Ozawa, Rie Saito, Takuya Konno, Reiji Koide, Shigeru Fujimoto, Osamu Onodera, Akiyoshi Kakita

    Journal of neurology, neurosurgery, and psychiatry   2023.11

     More details

    Authorship:Corresponding author   Language:English  

    DOI: 10.1136/jnnp-2023-332419

    PubMed

    researchmap

  • V180I genetic Creutzfeldt-Jakob disease: Severe degeneration of the inferior olivary nucleus in an autopsied patient with identification of the M2T prion strain. Reviewed International journal

    Midori Watanabe, Kosei Nakamura, Rie Saito, Atsuko Takeuchi, Tetsuya Takahashi, Tetsuyuki Kitamoto, Osamu Onodera, Akiyoshi Kakita

    Neuropathology : official journal of the Japanese Society of Neuropathology   2023.5

     More details

    Authorship:Corresponding author   Language:English  

    Genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2-thalamic-type sporadic CJD (sCJD-MM2T) involving type 2 prion protein (M2T prion). Here we report on an 81-year-old Japanese woman who initially developed depressive symptoms followed by progressive cognitive impairment, myoclonus, and hallucinations and died after a clinical course of 23 months. Insomnia was not evident. Genetic analysis of the prion protein (PrP) identified a V180I mutation with methionine/valine heterozygosity at codon 129. Pathologic analysis demonstrated extensive spongiform degeneration, neuronal loss in the cortices, and weak synaptic-type PrP deposition. Except for IO degeneration, the clinicopathologic features and Western blotting PrP band pattern were compatible with those of previously reported V180I gCJD cases. Quantitative analysis revealed that the neuronal density of the IO, especially in the dorsal area, was considerably reduced to the same extent as that of a patient with sCJD-MM2T but preserved in other patients with V180I gCJD and sCJD-MM1 (this patient, 2.3 ± 0.53/mm2 ; a patient with sCJD-MM2T, 4.2 ± 2; a patient with V180I gCJD, 60.5 ± 9.3; and a patient with sCJD-MM1, 84.5 ± 17.9). Use of the protein misfolding cyclic amplification (PMCA) method confirmed the presence of the M2T prion strain, suggesting that the latter might be associated with IO degeneration in V180I gCJD. Autopsy studies are necessary to better understand the nature of CJD, since even if patients present with the common clinical picture, pathologic analysis might provide new insights, as was the case here.

    DOI: 10.1111/neup.12908

    PubMed

    researchmap

  • SYNE1-ataxia: clinicopathologic features of an autopsied patient with novel compound heterozygous mutations Reviewed

    Rie Saito, Norikazu Hara, Mari Tada, Masatoshi Wakabayashi, Akinori Miyashita, Masatoyo Nishizawa, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Journal of Neuropathology & Experimental Neurology   2023.2

     More details

    Authorship:Lead author   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    DOI: 10.1093/jnen/nlac120

    researchmap

  • Spinocerebellar ataxia type 17-digenic TBP/STUB1 disease: neuropathologic features of an autopsied patient Reviewed International journal

    Rie Saito, Yui Tada, Daisuke Oikawa, Yusuke Sato, Makiko Seto, Akira Satoh, Kodai Kume, Nozomi Ueki, Masahiro Nakashima, Shintaro Hayashi, Yasuko Toyoshima, Fuminori Tokunaga, Hideshi Kawakami, Akiyoshi Kakita

    Acta Neuropathologica Communications   10 ( 1 )   177 - 177   2022.12

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Spinocerebellar ataxia (SCA) type 17-digenic TBP/STUB1 disease (SCA17-DI) has been recently segregated from SCA17, caused by digenic inheritance of two gene mutations – intermediate polyglutamine-encoding CAG/CAA repeat expansions (polyQ) in TBP (TBP<sub>41 − 49</sub>) and STUB1 heterozygosity – the former being associated with SCA17, and the latter with SCA48 and SCAR16 (autosomal recessive). In SCA17, most patients carry intermediate TBP<sub>41 − 49</sub> alleles but show incomplete penetrance, and the missing heritability can be explained by a new entity whereby TBP<sub>41 − 49</sub> requires the STUB1 variant to be symptomatic. The STUB1 gene encodes the chaperone-associated E3 ubiquitin ligase (CHIP) involved in ubiquitin-mediated proteasomal control of protein homeostasis. However, reports of the neuropathology are limited and role of STUB1 mutations in SCA17-DI remain unknown. Here we report the clinicopathologic features of identical twin siblings, one of whom was autopsied and was found to carry an intermediate allele (41 and 38 CAG/CAA repeats) in TBP and a heterozygous missense mutation in STUB1 (p.P243L). These patients developed autosomal recessive Huntington’s disease-like symptoms. Brain MRI showed diffuse atrophy of the cerebellum and T2WI revealed hyperintense lesions in the basal ganglia and periventricular deep white matter. The brain histopathology of the patient shared features characteristic of SCA17, such as degeneration of the cerebellar cortex and caudate nucleus, and presence of 1C2-positive neurons. Here we show that mutant CHIP fails to generate the polyubiquitin chain due to disrupted folding of the entire U box domain, thereby affecting the E3 activity of CHIP. When encountering patients with cerebellar ataxia, especially those with Huntington’s disease-like symptoms, genetic testing for STUB1 as well as TBP should be conducted for diagnosis of SCA17-DI, even in cases of sporadic or autosomal recessive inheritance.

    DOI: 10.1186/s40478-022-01486-6

    PubMed

    researchmap

    Other Link: https://link.springer.com/article/10.1186/s40478-022-01486-6/fulltext.html

  • Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model. Reviewed International journal

    Taisuke Kato, Ri-Ichiroh Manabe, Hironaka Igarashi, Fuyuki Kametani, Sachiko Hirokawa, Yumi Sekine, Natsumi Fujita, Satoshi Saito, Yusuke Kawashima, Yuya Hatano, Shoichiro Ando, Hiroaki Nozaki, Akihiro Sugai, Masahiro Uemura, Masaki Fukunaga, Toshiya Sato, Akihide Koyama, Rie Saito, Atsushi Sugie, Yasuko Toyoshima, Hirotoshi Kawata, Shigeo Murayama, Masaki Matsumoto, Akiyoshi Kakita, Masato Hasegawa, Masafumi Ihara, Masato Kanazawa, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera

    The Journal of clinical investigation   131 ( 22 )   2021.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

    DOI: 10.1172/JCI140555

    PubMed

    researchmap

  • Long Spinal Cord Lesions Caused by Venous Congestive Myelopathy Associated with Intravascular Large B-cell Lymphoma. Reviewed

    Takeshi Miura, Shoji Saito, Rie Saito, Tomohiro Iwasaki, Naomi Mezaki, Tomoe Sato, Yoichi Ajioka, Akiyoshi Kakita, Takuya Mashima

    Internal medicine (Tokyo, Japan)   2021.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Intravascular large B-cell lymphoma (IVLBCL) is a subtype of B-cell lymphoma, characterized by lymphoma cell proliferation within small blood vessels. We herein describe a rare case with long spinal cord lesions caused by venous congestive myelopathy associated with IVLBCL. An 81-year-old man presented with paraplegia of the lower limbs and sensory disturbances. Magnetic resonance imaging revealed intramedullary longitudinal T2-hyperintensity lesions in the thoracic cords. The patient died three months after disease onset, and a neuropathological analysis revealed predominantly atypical B-lymphocytes located sparsely in the veins of the spinal cord. IVLBCL should be considered in the differential diagnoses of long spinal cord lesions.

    DOI: 10.2169/internalmedicine.6717-20

    PubMed

    researchmap

  • Novel CHP1 mutation in autosomal-recessive cerebellar ataxia: autopsy features of two siblings. Reviewed International journal

    Rie Saito, Norikazu Hara, Mari Tada, Yoshiaki Honma, Akinori Miyashita, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Acta neuropathologica communications   8 ( 1 )   134 - 134   2020.8

     More details

    Authorship:Lead author, Corresponding author   Language:English  

    DOI: 10.1186/s40478-020-01008-2

    PubMed

    researchmap

  • Oculopharyngodistal myopathy with coexisting histology of systemic neuronal intranuclear inclusion disease: Clinicopathologic features of an autopsied patient harboring CGG repeat expansions in LRP12. Reviewed International journal

    Rie Saito, Hiroshi Shimizu, Takeshi Miura, Norikazu Hara, Naomi Mezaki, Yo Higuchi, Akinori Miyashita, Izumi Kawachi, Kazuhiro Sanpei, Yoshiaki Honma, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

    Acta neuropathologica communications   8 ( 1 )   75 - 75   2020.6

     More details

    Authorship:Lead author   Language:English  

    DOI: 10.1186/s40478-020-00945-2

    PubMed

    researchmap

  • Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy. Reviewed International journal

    Kanemaru Y, Natsumeda M, Okada M, Saito R, Kobayashi D, Eda T, Watanabe J, Saito S, Tsukamoto Y, Oishi M, Saito H, Nagahashi M, Sasaki T, Hashizume R, Aoyama H, Wakai T, Kakita A, Fujii Y

    Acta neuropathologica communications   7 ( 1 )   119 - 119   2019.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations - BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.

    DOI: 10.1186/s40478-019-0774-7

    PubMed

    researchmap

  • Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation. Reviewed

    Rie Saito

    Bioorganic & medicinal chemistry letters   29 ( 15 )   1886 - 1890   2019.5

     More details

    Publishing type:Research paper (scientific journal)  

    Three-dimensional (3D) imaging based on chemical tissue clearing in the post-mortem human brain is a promising approach for stereoscopic understanding of central nervous system diseases. Especially, delipidation of lipid-rich white matter (WM) is a rate-determining step in human brain clearing by hydrophilic reagents. In this study, we described the rapid delipidation of WM by a 1,2-hexanediol (HxD)-based aqueous solution. HxD delipidation enabled rapid clearing of a formalin-fixed human brain specimen including the WM. Although harsh HxD delipidation was applied to the brain tissue, conventional pathological staining patterns and various types of antigenicity were sufficiently preserved. Furthermore, HxD delipidation was compatible with 3D imaging of fluorescently-labeled tissue samples. HxD delipidation could be useful in future 3D neuropathological diagnosis.

    DOI: 10.1016/j.bmcl.2019.05.049

    PubMed

    researchmap

  • Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation. Reviewed

    Rie Saito

    Journal of neuropathology and experimental neurology   2019.2

     More details

    Authorship:Lead author   Publishing type:Research paper (scientific journal)  

    Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area, but translocates into the nucleus in response to oxidative DNA damage. It has been speculated that aberrant localization of the protein may be associated with systemic microangiopathy in patients with RVCL. However, cellular expression of TREX1 in the brain and visceral organs of patients with RVCL has been unclear. Here, we report the clinicopathologic features of an autopsied patient with a heterozygous T249fs mutation in TREX1. The patient showed the clinical phenotype of vasculopathy with retinopathy, nephropathy, and stroke. CT with contrast enhancement demonstrated a tumorous lesion in the subcortical white matter. Histologically, the lesion consisted of confluent foci of necrosis with calcification and fibrous thickening of small vessel walls. TREX1 immunohistochemistry demonstrated positivity in the nuclei of cells in the CNS and visceral organs, indicating aberrant localization of the truncated protein, and the expression was remarkable in oligodendrocytes within the lesion, suggesting possible involvement of the protein in the pathomechanism of vasculopathy leading to white matter degeneration.

    DOI: 10.1093/jnen/nly115

    PubMed

    researchmap

  • Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents. Reviewed International journal

    Kazuki Tainaka, Tatsuya C Murakami, Etsuo A Susaki, Chika Shimizu, Rie Saito, Kei Takahashi, Akiko Hayashi-Takagi, Hiroshi Sekiya, Yasunobu Arima, Satoshi Nojima, Masako Ikemura, Tetsuo Ushiku, Yoshihiro Shimizu, Masaaki Murakami, Kenji F Tanaka, Masamitsu Iino, Haruo Kasai, Toshikuni Sasaoka, Kazuto Kobayashi, Kohei Miyazono, Eiichi Morii, Tadashi Isa, Masashi Fukayama, Akiyoshi Kakita, Hiroki R Ueda

    Cell reports   24 ( 8 )   2196 - 2210   2018.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification. The strategic integration of optimal chemical cocktails provided a series of CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) protocols, which efficiently clear mouse organs, mouse body including bone, and even large primate and human tissues. The updated CUBIC protocols are scalable and reproducible, and they enable three-dimensional imaging of the mammalian body and large primate and human tissues. This strategy represents a future paradigm for the rational design of hydrophilic clearing cocktails that can be used for large tissues.

    DOI: 10.1016/j.celrep.2018.07.056

    PubMed

    researchmap

  • Renal histopathological findings of retinal vasculopathy with cerebral leukodystrophy. Reviewed

    Tsubata Y, Morita T, Morioka T, Sasagawa T, Ikarashi K, Saito N, Shimada H, Miyazaki S, Sakai S, Tanaka H, Saito R, Toyoshima Y, Nozaki H, Narita I

    CEN case reports   7 ( 1 )   83 - 89   2018.5

  • Loss of Motor Neurons Innervating Cervical Muscles in Patients With Multiple System Atrophy and Dropped Head. Reviewed

    Rie Saito

    Journal of neuropathology and experimental neurology   77 ( 4 )   317 - 324   2018.4

     More details

    Authorship:Lead author   Publishing type:Research paper (scientific journal)  

    We investigated whether loss of motor neurons innervating the neck muscles contributes to dropped head (DH) in multiple system atrophy (MSA). From 75 patients with autopsy-proven MSA, we retrieved 3 who had DH (MSA-DH), and examined the 4th cervical cord segments. Neurons of the medial and lateral nuclear groups (MNG and LNG) innervate the neck and shoulder muscles, respectively. We measured the area of individual neurons in the MNG and LNG, and created an area-frequency histogram. Neurons were classified as large or small based on their area, and their total numbers in the MNG and LNG were counted. In the MNG, the numbers of both total neurons and large neurons were significantly lower in MSA patients than in the controls (214.2 ± 91.4 vs 521.3 ± 74.8, p = 0.0030, and 26.2 ± 9.1 vs 88.0 ± 34.6, p = 0.020, respectively), and were significantly lower in MSA-DH than in MSA-nonDH (139.7 ± 7.6 vs 288.7 ± 74.6, p = 0.048, and 18.0 ± 4.1 vs 34.3 ± 4.1, p = 0.016, respectively). There were no differences in the LNG neuron counts between the MSA-DH and MSA-nonDH groups. Loss of cervical motor neurons may be responsible for DH in MSA.

    DOI: 10.1093/jnen/nly007

    PubMed

    researchmap

  • Nonfunctional intra- and suprasellar tumor in a patient with visual disturbance and panhypopituitarism. Reviewed

    Rie Saito

    Neuropathology : official journal of the Japanese Society of Neuropathology   36 ( 1 )   107 - 112   2015.8

     More details

    Authorship:Lead author   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/neup.12236

    PubMed

    researchmap

  • [A case of 77-year-old male with spinocerebellar ataxia type 31 with left dominant dystonia]. Reviewed

    Rie Saito, Shota Kikuno, Meiko Maeda, Yoshikazu Uesaka, Masahiro Ida

    Rinsho shinkeigaku = Clinical neurology   54 ( 8 )   643 - 7   2014

     More details

    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)  

    We report on the case of a 77-year-old male with genetically proven spinocerebellar ataxia type 31 (SCA31) who had dystonia. He was referred to our hospital for evaluation following a 6-year history of slowly progressive unsteadiness of his left leg during walking and dysarthria at the age of 62 years old. On the basis of his symptoms, we diagnosed him as spinocerebellar degeneration (SCD), and prescribed taltirelin hydrate. However, his symptoms continued to worsen. He required a cane for walking at the age of 63 years, and a wheelchair at the age of 66 years. He was admitted to our hospital following acute cerebral infarction at the age of 77 years. On examination at admission, right hemiparesis and cerebellar ataxia were detected. And left hallux moved involuntarily toward the top surface of the foot at rest, that is dystonia. The dystonia was not associated with cerebral infarction, because it had been several years with dystonia that he got cerebral infarction. Genetic analysis revealed that this patient harbored a heterozygous SCA31 mutation. Previously there have been no reports of SCA31 associated with dystonia. Our case report support clinical heterogeneity of SCA31, and highlight the importance of considering this type in patients with dystonia and ataxia. Patients with the combination of dystonia and ataxia and a family history of a neurodegenerative disorder should be tested for SCA31.

    PubMed

    researchmap

▶ display all

Books

  • 中枢神経 (非腫瘍性疾患病理アトラス)

    齋藤 理恵( Role: Contributor ,  脊髄小脳失調症6型; HTRA1関連脳小血管病)

    2024.3 

     More details

MISC

▶ display all

Presentations

  • Neuropathology of Oculopharyngodistal Myopathy Invited

    Rie Saito, Akiyoshi Kakita

    Joint Conference of the 22nd Annual Meeting of Asian Oceanian Myology Center and the 10th Annual Meeting of Japan Muscle Society  2024.9 

     More details

    Presentation type:Symposium, workshop panel (nominated)  

    researchmap

  • 3Dデジタル病理学構築と加齢性脳疾患/脳小血管病の理解 Invited

    齋藤理恵

    第三回日本医学会連合 Rising Starリトリート  2024.6 

     More details

    Presentation type:Oral presentation (invited, special)  

    researchmap

  • 脳血管障害の病理 -脳梗塞と脳出血を中心に- Invited

    齋藤理恵

    日本病理学会診断病理サマーフェスト  2023.9 

     More details

    Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    researchmap

  • HTRA1-related small vessel disease: vascular degeneration revealed by 3D pathologic analysis and fibulin5 immunostaining

    R Saito, T Kato, M Uemura, Y Saito, S Murayama, K Tainaka, O Onodera, A Kakita

    American Association of Neuropathologists  2023.6 

     More details

    Presentation type:Poster presentation  

    researchmap

  • Gordon Holmes syndrome and SCA17-DI: pathology of 2 unrelated patients with Huntington-like disorder

    Rie Saito, Yui Tada, Daisuke Oikawa, Yusuke Sato, Keisuke Iwanaga, Akira Satoh, Makiko Seto, Kodai Kume, Nozomi Ueki, Masahiro Nakashima, Shintaro Hayashi, Yasuko Toyoshima, Fuminori Tokunaga, Hideshi Kawakami, Akiyoshi Kakita

    The 64rd annual meeting of the Japanese Society of Neuropathology  2023.6 

     More details

    Presentation type:Oral presentation (general)  

    researchmap

  • Pathologic analysis for a better understanding of the pathophysiology of small vessel diseases

    2023.5 

     More details

    Presentation type:Symposium, workshop panel (public)  

    researchmap

  • 脳血管障害 Invited

    齋藤理恵

    神経病理学会教育講演  2022.6 

     More details

    Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    researchmap

  • Fibrin5 immunoprofiles in terms of diagnosis of HTRA1-related small vessel disease

    2022.6 

     More details

    Presentation type:Oral presentation (general)  

    researchmap

  • 脊髄小脳変性症:見てみよう神経病理 Invited

    齋藤理恵

    神経学会学術集会  2022.5 

     More details

    Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    researchmap

  • Vascular dementia: 3D histopathologic analysis of degenerative vasculature and white matter in cerebral small vessel diseases Invited

    Rie Saito

    Australian-Japan Collaboration in Dementia Research Workshop  2021.12 

     More details

    Presentation type:Oral presentation (invited, special)  

    researchmap

  • Cerebral small vessel disease: white matter degeneration revealed by 3D histopathologic evaluation

    Rie Saito

    The 62nd annual meeting of the Japanese Society of Neuropathology  2021.5 

     More details

  • 3D histopathologic analysis of degenerative vasculature and white matte in small-vessel diseases

    Rie Saito, Akiyoshi Kakita

    The 10thNIPS-PRI-BRINU. joint Symposium  2021.3 

     More details

  • 孤発性脳小血管病とCADASIL:剖検脳の白質変性に関する組織像の定量的解析

    齋藤 理恵

    第60回神経病理学会総会  2019.7 

     More details

  • Small vessel characteristics of autopsied patients with CADASIL and those heterozygous for HTRA1 mutations: 3D analysis using the Cubic tissue clearing technique

    Rie Saito, Kazuki Tainaka, Akiyoshi Kakita

    American Academy of Neurology, 2019 annual meeting  2019.5 

     More details

  • CADASIL and CARASIL Invited International conference

    齋藤 理恵

    19th International Congress of Neuropathology  2018.9 

     More details

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    researchmap

▶ display all

Awards

  • 優秀口演賞

    2024.6   第三回日本医学会連合Rising Starリトリート   3Dデジタル病理学構築と加齢性脳疾患/脳小血管病の理解

     More details

  • Excellent English oral presentation Award

    2021.5   Japanese society of Neuropathology   cerebral small vessel disease: white matter degeneration revealed by 3D histopathologic evaluation

     More details

  • 第57回神経病理学会総会学術研究会 優秀ポスター賞

    2016.6   日本神経病理学会  

    齋藤 理恵

     More details

Research Projects

  • Understanding Human 3D Cerebral Vascular Network Frailty in Small Vessel Disease (SVD)

    Grant number:24K10617

    2024.4 - 2028.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

      More details

    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    researchmap

  • 脳小血管の細胞外基質の摂動を起こす細胞群の同定と、その制御機構の解読

    Grant number:22H00466

    2022.4 - 2025.3

    System name:科学研究費助成事業

    Research category:基盤研究(A)

    Awarding organization:日本学術振興会

    小野寺 理, 加藤 泰介, 塚田 啓道, 齋藤 理恵

      More details

    Grant amount:\42510000 ( Direct Cost: \32700000 、 Indirect Cost:\9810000 )

    researchmap

  • Cerebral microangiopathy: To clarify the pathologic basis and pathomechanism

    Grant number:20K16595

    2020.4 - 2024.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

    Research category:Grant-in-Aid for Early-Career Scientists

    Awarding organization:Japan Society for the Promotion of Science

      More details

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    researchmap

  • Development of "3D Digital Neuropathology" as a new academic field

    Grant number:20K20468

    2019.6 - 2022.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Pioneering)

    Research category:Grant-in-Aid for Challenging Research (Pioneering)

    Awarding organization:Japan Society for the Promotion of Science

    Kakita Akiyoshi

      More details

    Grant amount:\25870000 ( Direct Cost: \19900000 、 Indirect Cost:\5970000 )

    The brain is a complex structure, and its functional units are especially three-dimensional. In this study, we developed a technological platform to capture the arrangement and network of neurons and glial cells, as well as the distribution of microvessels, in three dimensions by using transparency of human brain tissue and 3D imaging technology. First, we overcame the biggest optical challenges in human brain tissue, autofluorescence and browning, and succeeded in developing transparency reagents specifically for human brain tissue. Next, we established various general fluorescent staining and whole-mount immunostaining techniques for 3D. As a result, we have established an imaging platform for whole-mount visualization of many types of structures, including neurons, glial cells, microvessels, myelin sheaths, and senile plaques.

    researchmap

  • 血管性認知症:脳小血管病の臨床病理診断基準の確立へ向けて

    2018.8 - 2020.3

    System name:科学研究費:研究活動スタート支援

    Awarding organization:日本学術振興会

    齋藤 理恵

      More details

    Authorship:Principal investigator  Grant type:Competitive

    researchmap

Other research activities

 

Media Coverage

  • アルツハイマー病は“脳血管障害”!? 認知症の原因・治療法 最新研究 TV or radio program

    NHK  サイエンスZERO  2023.6

     More details

    Author:Myself 

    researchmap