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Intake of 7,8-dihydroxyflavone during juvenile and adolescent stages prevents onset of psychosis in adult offspring after maternal immune activation

Journal Article


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Abstract


  • Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC). Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the prelimbic (PrL) of medial PFC and CA1 of hippocampus. Supplementation of a TrkB agonist 7,8-dihydroxyflavone (1 mg/mL in drinking water) during juvenile and adolescent stages could prevent these behavioral abnormalities, reduced BDNF-TrkB signaling in PFC and CA1, and immunoreactivity of PV and PGC-1α in the PrL of medial PFC and CA1 in the adult offspring from poly(I:C)-treated mice. These findings suggest that early intervention by a TrkB agonist in subjects with ultra-high risk for psychosis may reduce the risk of subsequent transition to schizophrenia.

Authors


  •   Han, Mei
  •   Zhang, Ji-chun (external author)
  •   Yao, Wei (external author)
  •   Yang, Chun (external author)
  •   Ishima, Tamaki (external author)
  •   Ren, Qian (external author)
  •   Ma, Min (external author)
  •   Dong, Chao (external author)
  •   Huang, Xu-Feng
  •   Hashimoto, Kenji (external author)

Publication Date


  • 2016

Citation


  • Han, M., Zhang, J., Yao, W., Yang, C., Ishima, T., Ren, Q., Ma, M., Dong, C., Huang, X. & Hashimoto, K. (2016). Intake of 7,8-dihydroxyflavone during juvenile and adolescent stages prevents onset of psychosis in adult offspring after maternal immune activation. Scientific Reports, 6 36087-1-36087-10.

Scopus Eid


  • 2-s2.0-84994462232

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1958&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/933

Has Global Citation Frequency


Start Page


  • 36087-1

End Page


  • 36087-10

Volume


  • 6

Place Of Publication


  • United Kingdom

Abstract


  • Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC). Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the prelimbic (PrL) of medial PFC and CA1 of hippocampus. Supplementation of a TrkB agonist 7,8-dihydroxyflavone (1 mg/mL in drinking water) during juvenile and adolescent stages could prevent these behavioral abnormalities, reduced BDNF-TrkB signaling in PFC and CA1, and immunoreactivity of PV and PGC-1α in the PrL of medial PFC and CA1 in the adult offspring from poly(I:C)-treated mice. These findings suggest that early intervention by a TrkB agonist in subjects with ultra-high risk for psychosis may reduce the risk of subsequent transition to schizophrenia.

Authors


  •   Han, Mei
  •   Zhang, Ji-chun (external author)
  •   Yao, Wei (external author)
  •   Yang, Chun (external author)
  •   Ishima, Tamaki (external author)
  •   Ren, Qian (external author)
  •   Ma, Min (external author)
  •   Dong, Chao (external author)
  •   Huang, Xu-Feng
  •   Hashimoto, Kenji (external author)

Publication Date


  • 2016

Citation


  • Han, M., Zhang, J., Yao, W., Yang, C., Ishima, T., Ren, Q., Ma, M., Dong, C., Huang, X. & Hashimoto, K. (2016). Intake of 7,8-dihydroxyflavone during juvenile and adolescent stages prevents onset of psychosis in adult offspring after maternal immune activation. Scientific Reports, 6 36087-1-36087-10.

Scopus Eid


  • 2-s2.0-84994462232

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1958&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/933

Has Global Citation Frequency


Start Page


  • 36087-1

End Page


  • 36087-10

Volume


  • 6

Place Of Publication


  • United Kingdom