Probing the mechanism of reduced serotonin transporter densities in autistic brains : a postmortem brain study

• Project/Area Number: 21791125
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUDA Shiro Hamamatsu University School of Medicine, 子どものこころの発達研究センター, 助教 (40432207)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 児童 / 思春期精神医学 / 自閉症 / 死後脳研究 / セロトニン神経 / トランスポーター / 蛋白発現解析

Research Abstract

Emerging evidence from neuroimaging study using positron emission tomography (PET) suggests reduced serotonin transporter (SERT) densities in the brains of subjects with autism. To probe the mechanism of reduced SERT densities in autistic brains、we examined the postmortem brains of autistic subjects to identify any changes in the expression of SERT proteins. mRNA and protein expression of SERT protein were examined in the autistic brain and control subjects using real time PCR and Western blotting. The result showed that none of mRNA and protein expression was found to be significantly altered. Since PET tracers bind the membrane expressed SERT proteins, this finding suggests that dysregulation of protein transport, trafficking and transporter internalizing systems may underlie the reduced SERT densities in autistic brains.

Research Products

• [Journal Article] Searching for very early precursors of autism spectrum disorders : the Hamamatsu Birth Cohort for Mothers and Children (HBC). (2010)
  • Author(s): Tsuchiya KJ, Matsumoto K, Suda S, Miyachi T, Itoh H, Kanayama N, Hirano K, Ohzeki T, Takei N, the HBC Study Team.
  • Journal Title: Journal of Developmental Origins of Health and Disease 1 Pages: 158-173
• [Journal Article] Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats : reversal by fluoxetine. (2010)
  • Author(s): Suzuki K, Okada K, Wakuda T, Shinmura C, Kameno Y, Iwata K, Takahashi T, Suda S, Matsuzaki H, Iwata Y, Hashimoto K, Mori N.
  • Journal Title: PLoS ONE 5
  • NAID: 120005314217
• [Journal Article] Donepezil and concurrent sertraline treatment is associated with increased volume of the hippocampi in a patient with depression. (2010)
  • Author(s): Suda S, Sugihara G, Suyama R, Mori N, Takei N.
  • Journal Title: J Clin Psychiatry 71 Pages: 806-808
• [Journal Article] Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. (2010)
  • Author(s): Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, Tsuchiya KJ, Sugihara G, Iwata Y, Suzuki K, Matsuzaki H, Suda S, Sugiyama T, Takei N, Mori N.
  • Journal Title: Arch Gen Psychiatry 67 Pages: 59-68
• [Journal Article] Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autism. (2010)
  • Author(s): Kajizuka M, Miyachi T, Matsuzaki H, Iwata K, Shinmura C, Suzuki K, Suda S, Tsuchiya KJ, Matsumoto K, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 34 Pages: 154-158
• [Journal Article] Decreased serum levels of adiponectin in subjects with autism. (2010)
  • Author(s): Fujita-Shimizu A, Suzuki K, Nakamura K, Miyachi T, Matsuzaki H, Kajizuka M, Shinmura C, Iwata Y, Suda S, Tsuchiya KJ, Matsumoto K, Sugihara G, Iwata K, Yamamoto S, Tsujii M, Sugiyama T, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 34 Pages: 455-458
• [Journal Article] Donepezil and concurrent sertraline treatment is associated with increased volume of the hippocampi in a patient with depression. (2010)
  • Author(s): Suda S, et al.
  • Journal Title: J Clin Psychiatry Volume: 71 Pages: 806-808
  • Peer Reviewed
• [Journal Article] Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats : reversal by fluoxetine. (2010)
  • Author(s): Suzuki K, et al.
  • Journal Title: Plos One Volume: 5
  • Peer Reviewed
• [Journal Article] Searching for very early precursors of autism spectrum disorders : the Hamamatsu Birth Cohort for Mothers and Children (HBC). (2010)
  • Author(s): Tsuchiya KJ, et al.
  • Journal Title: J DOHaD Volume: 1 Pages: 158-173
  • Peer Reviewed
• [Journal Article] Donepezil and concurrent sertraline treatment is associated with increased volume of the hippocampi in a patient with depression. (2010)
  • Author(s): Suda S, et al.
  • Journal Title: J Clin Psychiatry (印刷中)
  • Peer Reviewed
• [Journal Article] Brain serotonin and dopamine transporter bindings in adults with high-functioning autism (2010)
  • Author(s): Nakamura K, et al.
  • Journal Title: Arch Gen Psychiatry 67 Pages: 59-68
  • Peer Reviewed
• [Journal Article] Decreased serum levels of adiponectin in subjects with autism. (2010)
  • Author(s): Fujita-Shimizu, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 34 Pages: 455-458
  • Peer Reviewed
• [Journal Article] Dysregulation of the Peripheral Glutamatergic System in Children with Autism.
  • Author(s): Shimmura C, Suda S, Tsuchiya KJ, Hashimoto K, Ohno K, Matsuzaki H, Iwata K, Matsumoto K, Wakuda T, Kameno Y, Suzuki K, Tsujii M, Nakamura K, Takei N, Mori N.
  • Journal Title: PLoS ONE (投稿中)
• [Presentation] Dysregulation of glutamatergic biosynthetic pathway in subjects with autism. (2010)
  • Author(s): Shimmura C, Suda S, et al
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2010-11-16
• [Presentation] Dysregulation of glutamatergic biosynthetic pathway in subjects with autism.Neuroscience 2010 (2010)
  • Author(s): Shimmura C, Suda S, Tsuchiya KJ, Hashimoto K, Matsuzaki H, Iwata Y, Kameno Y, Nakamura K, Takei N, Mori N.
  • Organizer: the 40^<th> Annual Meeting of the Society for Neuroscience
  • Place of Presentation: SanDiego, CA, USA
• [Presentation] Serotonin related gene expression changes in subjects with autism : A postmortem brain study (2009)
  • Author(s): Suda S, et al.
  • Organizer: Neuroscience 2009
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2009-10-19
• [Presentation] Serotonin related gene expression changes in subjects with autism: A postmortem brain study. (2009)
  • Author(s): Suda S, Iwata K, Anitha A, Thanseem I, Nakamura K, Matsuzaki H, Iwata Y, Yamamoto S, Suzuki K, Takei N, Mori N.
  • Organizer: Neuroscience 2009, the 39^<th> Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, IL, USA
• [Book] Handbook of Behavior, Food and Nutrition(Disturbed growth in early life and later neurocognitive development associated with psychiatric disorders.)(Preedy VR, Watson RR, Martin CR (Eds.))chapter 100 New York (2011)
  • Author(s): Suda S, Takei N.
  • Publisher: Springer
• [Book] Handbook of Behavior, Food and Nutrition (book chapter) (2011)
  • Author(s): Suda S, Takei N
  • Total Pages: 16
  • Publisher: Springer, New York
• [Book] International Handbook of Behavior, Diet, and Nutrition (book chapter) (2010)
  • Author(s): Suda S, Takei N
  • Publisher: Springer(印刷中)