Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation

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.

7,8-Dihydroxyflavone facilitates the action exercise to restore plasticity and functionality: Implications for early brain trauma recovery

“…The present study demonstrates that 7,8-DHF greatly complements the action of exercise to enhance PGC-1α levels, which could help to fulfill the energy demands imposed by TBI. A recent report indicates the ability of 7,8-DHF to augment PGC-1α immunoreactivity in the hippocampal cornus ammonis area 1 (CA1), which could be important to regulate BDNF-mediated TrkB signaling [42]. This finding is consistent with the earlier data linking PGC-1α activation with BDNF expression [43].…”

Cognitive impairment and gene expression alterations in a rodent model of binge eating disorder

“…In our study, we found significant decreases in the FrC Bdnf and TrkB expression in BEP rats as compared to CON and DAILY groups respectively, and a significant decrease in the mPFC TrkB expression in BEP as compared to BER and CON groups. Two independent studies have demonstrated that Bdnf-trkB signaling in the prefrontal cortex is involved in regulating novel object recognition memory [39, 40]. In one study, exposure to 60% HFD in juvenile mice for as short as one week was associated with impairments in the NOR task as well as Y-maze based spatial working memory task with reduced prefrontal cortex Bdnf expression, despite no differences in body weight [20].…”

Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

“…Treatment schedule of poly(I:C) was performed according to our previous reports4254. Every six consecutive days from E12 to E17, the pregnant mice were injected intraperitoneally (i.p.)…”

“…Both horizontal and rearing activity were monitored by an infrared ray passive sensor system (SCANET-SV10, Melquest Ltd, Toyama, Japan), and activity was integrated every 10 minutes, as previously reported515456. Individual mice were placed in activity chambers and allowed 2 hours of free exploration as spontaneous activity.…”

“…The NORT was performed as previously reported51545758. Before testing, mice were habituated in the box for 3 days.…”