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

The glycine level in the brain is known to be altered in neuropsychiatric disorders, such as schizophrenia and Alzheimer’s disease (AD). Several studies have reported the in vivo measurement of glycine concentrations in the brain using proton magnetic resonance spectroscopy (1H-MRS), but 1H-MRS is not capable of imaging the distribution of glycine concentration with high spatial resolution. Chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) is a new technology that can detect specific molecules, including amino acids, in tissues. To validate the measurements of glycine concentrations in living tissues using CEST from glycine to water (GlyCEST), we extracted the brain tissues from mice and performed biochemical tests. In wild-type C57BL/6 mice, GlyCEST effects were found to be higher in the thalamus than in the cerebral cortex (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.0001</mn>
</math>
</inline-formula>, paired t-test), and this result was in good agreement with the biochemical results. In 5xFAD mice, an animal model of AD, GlyCEST measurements demonstrated that glycine concentrations in the cerebral cortex (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M2">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.05</mn>
</math>
</inline-formula>, unpaired t-test) and thalamus (<inline-formula>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="M3">
<mi>P</mi>
<mo>&lt;</mo>
<mn>0.0001</mn>
</math>
</inline-formula>, unpaired t-test), but not in the hippocampus, were decreased compared to those in wild-type mice. These findings suggest that we have successfully applied the CEST-MRI technique to map the distribution of glycine concentrations in the murine brain. The present method also captured the changes in cerebral glycine concentrations in mice with AD. Imaging the distribution of glycine concentrations in the brain can be useful in investigating and elucidating the pathological mechanisms of neuropsychiatric disorders.

DOI： 10.1155/2021/8988762

researchmap

Other Link： http://downloads.hindawi.com/journals/cmmi/2021/8988762.xml

Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

<bold>Background:</bold> Autonomous sensory meridian response (ASMR) is used by young people to induce relaxation and sleep and to reduce stress and anxiety; it comprises somatosensation caused by audiovisual stimuli (triggers) that lead to positive emotions. Auditory stimuli play the most important role among the triggers involved in ASMR and have been reported to be more triggering than visual stimuli. On the other hand, classical music is also known to have a relaxing effect. This is the first study to clarify the difference in brain activation associated with relaxation effects between ASMR and classical music by limiting ASMR to auditory stimulation alone.

<bold>Methods:</bold> Thirty healthy subjects, all over 20 years of age, underwent fMRI while listening to ASMR and classical music. We compared the differences in brain activation associated with classical music and ASMR stimulation. After the experiment, the subjects were administered a questionnaire on somatosensation and moods. After the experiment, the participants were asked whether they experienced ASMR somatosensation or frisson. They were also asked to rate the intensity of two moods during stimulation: “comfortable mood,” and “tingling mood”.

<bold>Result:</bold> The results of the questionnaire showed that none of the participants experienced any ASMR somatosensation or frisson. Further, there was no significant difference in the ratings given to comfort mood, but there was a significant difference in those given to tingling mood. In terms of brain function, classical music and ASMR showed significant activation in common areas, while ASMR showed activation in more areas, with the medial prefrontal cortex being the main area of activation during ASMR.

<bold>Conclusion:</bold> Both classical music and the ASMR auditory stimulus produced a pleasant and relaxed state, and ASMR involved more complex brain functions than classical music, especially the activation of the medial prefrontal cortex. Although ASMR was limited to auditory stimulation, the effects were similar to those of listening to classical music, suggesting that ASMR stimulation can produce a pleasant state of relaxation even if it is limited to the auditory component, without the somatic sensation of tingling. ASMR stimulation is easy to use, and appropriate for wellness purposes and a wide range of people.

DOI： 10.3389/fnbeh.2021.761621

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
Although brain gray matter (GM) plastically changes during short-term training, it is still unclear whether brain structures are stable for short periods (several months). Therefore, this study aimed to re-test the short-term variability of GM volumes and to clarify the effect of factors (gender and BDNF-genotype) expected to contribute to such variability. The subjects comprised 41 young healthy adults. T1-weighted images were acquired twice with an interval of approximately 4 months using a 3 T-MRI scanner. Voxel-based morphometry (VBM) was used to calculate GM volumes in 47 regions. The intraclass correlation coefficient (ICC) and Test–retest variability (%TRV) were used as indices of variability. As a result, the ICCs in 43 regions were excellent (ICC &amp;gt; 0.90) and those in 3 regions were good (ICC &amp;gt; 0.80), whereas the ICC in the thalamus was moderate (ICC = 0.694). Women had a higher %TRV than men in 5 regions, and %TRV of the Val66Val group was higher than that of the Met carrier group in 2 regions. Moreover, the Female-Val66Val group had a higher %TRV than the Male-Met carrier group in 3 regions. These results indicate that although the short-term variability of GM volumes is small, it is affected by within-subject factors.

DOI： 10.1093/cercor/bhab370

PubMed

researchmap

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

Individual motor performance ability is affected by various factors. Although the key factor has not yet completely been elucidated, the brain-derived neurotrophic factor (BDNF) genotype as well as neurometabolites may become contibuting factors depending on the learning stage. We investigated the effects of the Met allele of the BDNF gene and those of the neurometabolites on visuomotor learning. In total, 43 healthy participants performed a visuomotor learning task consisting of 10 blocks using the right index finger (Val66Val, n = 15; Val66Met, n = 15; and Met66Met, n = 13). Glutamate plus glutamine (Glx) concentrations in the primary motor cortex, primary somatosensory cortex (S1), and cerebellum were evaluated using 3-T magnetic resonance spectroscopy in 19 participants who participated in the visuomotor learning task. For the learning stage, the task error (i.e., learning ability) was significantly smaller in the Met66Met group compared with that observed in the remaining groups, irrespective of the learning stage (all p values < 0.003). A significant difference was observed between the Val66Val and Met66Met groups in the learning slope (i.e., learning speed) in the early learning stage (p = 0.048) but not in the late learning stage (all p values> 0.54). Moreover, positive correlations were detected between the learning slope and Glx concentrations in S1 only in the early learning stage (r = 0.579, p = 0.009). The BDNF genotype and Glx concentrations in S1 partially contribute to interindividual variability on learning speed in the early learning stage.

DOI： 10.1016/j.bbr.2021.113433

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The Met allele of the brain-derived neurotrophic factor (BDNF) gene confers reduced cortical BDNF expression and associated neurobehavioral changes. BDNF signaling influences the survival, development, and synaptic function of cortical networks. Here, we compared gamma-aminobutyric acid (GABA)ergic network activity in the human primary motor cortex (M1) between the Met (Val/Met and Met/Met) and non-Met (Val/Val) genotype groups. Short- and long-interval intracortical inhibition, short-latency afferent inhibition (SAI), and long-latency afferent inhibition were measured using transcranial magnetic stimulation (TMS) as indices of GABAergic activity. Furthermore, the considerable inter-individual variability in inhibitory network activity typically measured by TMS may be affected not only by GABA but also by other pathways, including glutamatergic and cholinergic activities; therefore, we used 3-T magnetic resonance spectroscopy (MRS) to measure the dynamics of glutamate plus glutamine (Glx) and choline concentrations in the left M1, left somatosensory cortex, and right cerebellum. All inhibitory TMS conditions produced significantly smaller motor-evoked potentials than single-pulses. SAI was significantly stronger in the Met group than in the Val/Val group. Only the M1 Glx concentration was significantly lower in the Met group, while the BDNF genotype did not affect choline concentration in any region. Further, a positive correlation was observed between SAI and Glx concentrations only in M1. Our findings provide evidence that the BDNF genotype regulates both the inhibitory and excitatory circuits in human M1. In addition, lower Glx concentration in the M1 of Met carriers may alter specific inhibitory network on M1, thereby influencing the cortical signal processing required for neurobehavioral functions.

DOI： 10.3390/brainsci11030395

researchmap

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

Many of the focal neurological symptoms associated with Alzheimer's disease (AD) are due to synaptic loss. Glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) is a candidate method to assess synaptic dysfunction. We assessed chronological changes in GluCEST in a 5xFAD mouse model of AD, comparing Glucest effects and regional cerebral blood flow (CBF). GluCEST effects and CBF in 5xFAD mice aged 1-15 months and their littermates (WT) were measured. Neurite orientation dispersion and density imaging (NODDI) MRI reflecting dendritic/axonal density was also measured and compared with GluCEST in 7-month-old mice. While regional CBF's decrease began at 7 months, GluCEST-reduction effects preceded hypoperfusion of the temporal cortex and hippocampus. While longitudinal 5xFAD mouse measurements revealed a correlation between the regional GluCEST effects and CBF, a generalized linear mixed model revealed statistically different correlations in cortical and basal brain regions. Further, NODDI-derived neurite density correlated with GluCEST effects in the parietal cortex, but not in the hippocampus, thereby revealing regional differences in pathophysiological mechanisms. Finally, GluCEST's effects correlated with regional synaptophysin. These results demonstrate that GluCEST can reflect subtle synaptic changes and may be a potential imaging method for AD diagnosis as well as serve as a biomarker of AD progression.

DOI： 10.1155/2020/8831936

PubMed

researchmap

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

Matrix metalloproteinases (MMPs) damage the neurovascular unit, promote the blood-brain barrier (BBB) disruption following ischemic stroke, and play essential roles in hemorrhagic transformation (HT), which is one of the most severe side effects of thrombolytic therapy. However, no biomarkers have presently been identified that can be used to track changes in the distribution of MMPs in the brain. Here, we developed a new 19F-molecular ligand, TGF-019, for visualizing the distribution of MMPs in vivo using 19F-magnetic resonance spectroscopic imaging (19F-MRSI). We demonstrated TGF-019 has sufficient sensitivity for the specific MMPs suspected in evoking HT during ischemic stroke, i.e., MMP2, MMP9, and MMP3. We then utilized it to assess those MMPs at 22 to 24 hours after experimental focal cerebral ischemia on MMP2-null mice, as well as wild-type mice with and without the systemic administration of the recombinant tissue plasminogen activator (rt-PA). The 19F-MRSI of TGN-019-administered mice showed high signal intensity within ischemic lesions that correlated with total MMP2 and MMP9 activity, which was confirmed by zymographic analysis of ischemic tissues. Based on the results of this study, 19F-MRSI following TGN-019 administration can be used to assess potential therapeutic strategies for ischemic stroke.

DOI： 10.1155/2019/8908943

PubMed

researchmap

Language：English  

DOI： 10.1272/jnms.84.160

Web of Science

PubMed

researchmap

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

DOI： 10.1120/jacmp.v13i6.3868

Web of Science

PubMed

researchmap

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

DOI： 10.11323/jjmp.30.2_39

researchmap

Event date： 2019.11

Language：Japanese  

researchmap

Event date： 2018.10

Language：Japanese  

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J03755&link_issn=&doc_id=20181023320088&doc_link_id=%2Fdq6ngtif%2F2018%2F001801%2F089%2F0103-0103%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdq6ngtif%2F2018%2F001801%2F089%2F0103-0103%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Event date： 2014.2

Language：Japanese  

researchmap

Event date： 2014.1

Language：Japanese  

researchmap

researchmap

researchmap

researchmap

Presentation type：Poster presentation  

researchmap

Presentation type：Poster presentation  

researchmap

researchmap

Language：English   Presentation type：Oral presentation (general)  

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap