子どものこころの発達研究センター
脳機能発達研究部門（松﨑研究室）の活動紹介
 私達は「自閉スペクトラム症（ASD）」の研究をしています。
 主に分子生物学を用いた基礎研究を行っていますが、当事者から集めた血液中のバイオマーカー解析や、研究成果を治療に結びつけるための臨床試験も手がけています。
 研究室は院生棟の1階にあり、医学部学生が多く出入りしています。

2022 ラボメンバー

ASDとセロトニン
当研究室は、NSF遺伝子のヘテロノックアウトマウスがASD様の行動や脳組織を示すことをつきとめました。

Iwata K, et al. Mol Autism , 2014.

ASD児童は血中VLDL脂質分画が少ない「低脂血症」を合併することを発見しました。

Xie MJ, et al. Front Genet, 2021.

ASDの脂質代謝
このときLPL活性の上昇、遊離脂肪酸の濃度上昇が認められたので、ASD児童では血中VLDLが分解され低脂血症になると推定されました。

Usui N, et al. EBioMedicine, 2020.

Hirai T, et al. Res Autism Spectr Disord , 2020.

ASDと酸化ストレス
多価不飽和脂肪酸(PUFA)は代謝が進むと活性酸素種(ROS)を介して炎症や酸化ストレスの制御に関わります。
ASD児童は血中のROS活性が特異的なパターンを示すことを発見し、判定技術として特許（特許6830578号）も取得しました。

ASDは酸化ストレスやミトコンドリア機能の異常を合併しやすいため、ミトコンドリア機能を高める5-アミノレブリン酸がASDの治療手段にならないかと考えました。5-アミノレブリン酸を18歳以上のASD者に投与する特定臨床研究【jRCTs051190017】を実施して有望な結果を得たため、いま児童対象の特定臨床研究を実施しています。

また、ASDの成因として「妊娠中の母体に生じる急性・慢性の炎症や酸化ストレスが引き起こす母体免疫活性化」にも着目し、臍
帯血出生コホートによって、ASDの発症に関わる臍帯血中の脂肪酸代謝物やROSを探索し、特定する試みを開始しています。

Hirayama A, et al. Sci Rep , 2020.

詳しい話は研究室で！

松﨑研が貢献した研究論文
2022年
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2021年
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disorder with brain structures. Front Neurosci. 12:799761, 2021.
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and increased anxiety. Front Genet. 12:754198, 2021.
 Xie MJ, et al. Autistic-like behavior and impairment of serotonintransporter and AMPA receptor trafficking in N-ethylmaleimide
sensitive factor gene-deficient mice. Front Genet. 2:748627, 2021.
 Tochitani S, et al. Fermented rice bran supplementation ameliorates
obesity via gut microbiota and metabolism modification in female mice.
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 Usui N, Matsuzaki H, Shimada S. Characterization of Early Life StressAffected Gut Microbiota. Brain Sci. 11(7), 913, 2021.
 Balan S, et al. A loss of function variant in SUV39H2 identified in
autism spectrum disorder causes altered H3K9-trimethylation anddysregulation of protocadherin β cluster genes in the developing brain.
Mol Psychiat. 26(12):7550-7559, 2021.
 Tochitani S , et al. GABAA receptors and maternally derived taurine
regulate the temporal specification of progenitors of excitatoryglutamatergic neurons in the mouse developing cortex. CerebralCortex. 31(10):4554-4575, 2021.
 Usui N, et al. Zbtb16 regulates social cognitive behaviors andneocortical development. Transl Psychiat. 11(1):242, 2021.
2020年
 Zaninello M et al. Inhibition of autophagy curtails visual loss in a modelof autosomal dominant optic atrophy. Nat Commun. 11(1):4029, 2020.
 Hirai T et al. Increased plasma lipoprotein lipase activity in males withautism spectrum disorder. Res Autism Spectr Disord. 77：101630, 2020.
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disorder correlate with social interaction. EBioMedicine. 58:102917,
2020.
 Maekawa M et al. A potential role of fatty acid binding protein 4 in thepathophysiology of autism spectrum disorder. Brain Commun. fcaa145,
2020.
 Fujioka T et al. Developmental changes in attention to social
information from childhood to adolescence in autism spectrum
disorders: A comparative study. Mol Autism. 11: 24, 2020.
2019年
 Yamashita Y, et al. Anti-inflammatory effect of ghrelin in
lymphoblastoid cell lines from children with autism spectrum disorder.
Front Psychiat. 10:152, 2019.
 Xie MJ, et al. PIP3-Phldb2 is crucial for LTP regulating synaptic NMDAand AMPA receptor density and PSD95 turnover. Sci Rep. 9(1):4305,
2019.
 Iwata K, et al. Mitochondrial Involvement in Mental Disorders: Energy
Metabolism, Genetic and Environmental Factors. Adv Exp Med Biol.
1118:63-70, 2019.
 Iwata K and Scorrano L: Finding a new balance to cure Charcot-MarieTooth 2A. J Clin Invest. 130: 1533-1535, 2019.
2018年
 Toritsuka M, et al. Altered gene expression in lymphoblastoid cell lines
after subculture. In Vitro Cell Dev Biol Anim. 54(7):523-527, 2018.
 Sugiura H, et al. Fibroblast growth factor 23 is upregulated in thekidney in a chronic kidney disease rat model. PLoS One.
13(3):e0191706, 2018.
 Nelissen TP, et al. CD38 is required for dendritic organisation in visualcortex and hippocampus. Neurosci. 372:114-125, 2018.
2017年
 Fontenot MR, et al. Novel transcriptional networks regulated by CLOCK
in human neurons. Genes Dev. 31(21):2121-2135, 2017.
 Paparelli A, et al. Perinatal asphyxia in rat alters expression of novel
schizophrenia risk genes. Front Mol Neurosci. 10:341, 2017.
 Usui N, et al. Foxp1 regulation of neonatal vocalizations via corticaldevelopment. Genes Dev. 31(20):2039-2055, 2017.
 Escamilla CO, et al. Kctd13 deletion reduces synaptic transmission via
increased RhoA. Nature. 551(7679):227-231, 2017.
 Araujo D, et al. Foxp1 in Forebrain Pyramidal Neurons Controls Gene
Expression Required for Spatial Learning and Synaptic Plasticity. JNeurosci. 37(45):10917-10931, 2017.
 Morimura N, et al. Autism-like behaviors and enhanced memory
formation and synaptic plasticity in Lrfn2/SALM1-deficient mice. NatCommun. 8:15800, 2017.
 Yagi H, et al. Subcellular distribution of non-muscle myosin IIb iscontrolled by FILIP through Hsc70. PLoS One. 12(2):e0172257, 2017.
 Andrade E, et al. ARPP-16 is a striatal-enriched inhibitor of protein
phosphatase 2A regulated by microtubule-associated serine/threonine
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 Ikawa D, et al. Microglia-derived neuregulin expression in psychiatricdisorders. Brain Behav Immun. 61:375-385, 2017.
2016年
 Makinodan M, et al. Tumor necrosis factor-alpha expression in
peripheral blood mononuclear cells correlates with early childhoodsocial interaction in autism spectrum disorder. Neurochem. Int. 104:15, 2017.
 Kameno Y, et al. Mismatch in cerebral blood flow and glucose
metabolism after the forced swim stress in rats. Acta Neuropsychiatr.
28(6):352-356, 2016.
 Mundalil Vasu M, et al. Fluoxetine Increases the Expression of miR-572
and miR-663a in Human Neuroblastoma Cell Lines. PLoS One.
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 Sato R, et al. Fetal Environment and Glycosylation Status in Neonatal
Cord Blood: A Comprehensive Mass Spectrometry-based Glycosylation
Analysis. Medicine (Baltimore). 95(14):e3219, 2016.
 Silva JC, et al. Effect of MK-801 and clozapine on the proteome ofcultured human oligodendrocytes. Front Cell Neurosci. 10: 52, 2016.
 Tochitani S, et al. Administration of Non-absorbable Antibiotics toPregnant Mice to Perturb the Maternal Gut Microbiota Is Associatedwith Alterations in Offspring Behavior. PLoS One. 11(1):e0138293,2016.
2015年
 Ishibashi Y, et al. Fluvoxamine reverses estrogen-dependent decline involuntary activities and decreased amygdala levels of serotonin in
ovariectomized rats. Journal of Brain Science. 46:5-19, 2016.
 Guest PC, et al. MK-801 treatment affects glycolysis inoligodendrocytes more than in astrocytes and neuronal cells: insights
for schizophrenia. Front Cell Neurosci. 9:180, 2015.
 Maekawa M, et al. Investigation of the fatty acid transporter-encoding
genes SLC27A3 and SLC27A4 in autism Sci Rep. 5: 16239, 2015.
 Maekawa M, et al. Utility of Scalp Hair Follicles as a Novel Source ofBiomarker Genes for Psychiatric Illnesses. Biol Psychiat. 78(2):116-125,2015.
 Wakuda T, et al. Perinatal asphyxia alters Neuregulin-1 and COMT gene
expression in the medial prefrontal cortex in rats. Prog
Neuropsychopharmacol Biol Psychiat. 56:149-54, 2015.
2014年
 Mundalil Vasu M, et al. Serum microRNA profiles in children withautism. Mol Autism. 5:40, 2014.
 Iwata K, et al. N-ethylmaleimide-sensitive factor interacts with theserotonin transporter and modulates its trafficking: implications forpathophysiology in autism. Mol Autism. 5:33, 2014.
 Terada K, et al. Fluvoxamine moderates reduced voluntary activity
following chronic dexamethasone infusion in mice via recovery ofBDNF signal cascades. Neurochem Int. 69:9-13, 2014.