Prenatal MAM treatment altered fear conditioning following social isolation: Relevance to schizophrenia.

Adolescent social isolation (SI) might change the trajectory of brain development. In the present study, we investigated the effect of short-term adolescent SI on fear memory, anxiety and protein levels in the adult medial prefrontal cortex of rats prenatally treated with methylazoxymethanol, MAM-E17 model of schizophrenia. The animals were maintained in standard housing (SH) or social isolation (P30-P40, SI) conditions.

Early-life blockade of NMDA receptors induces epigenetic abnormalities in the adult medial prefrontal cortex: possible involvement in memory impairment in trace fear conditioning.

Rationale: Several findings indicate that early-life dysfunction of N-methyl-D-aspartate (NMDA) receptors might cause schizophrenia-like abnormalities in adulthood that might be induced by impairments in epigenetic regulation.

Objectives: In the present study, we investigated whether postnatal blockade of NMDA receptors (within the first 3 weeks of life) by the competitive antagonist CGP 37849 (CGP) might affect some epigenetic markers in the adult medial prefrontal cortex (mPFC).

Methods: Histone H3 phosphorylation at serine 10 (H3S10ph), histone H3 acetylation at lysine 9 or 14 (H3K9ac or H3K14ac, respectively), or expression of histone deacetylase (HDAC) 2, HDAC5, myocyte enhancer factor (MEF) 2D and activity-regulated cytoskeleton-associated protein (Arc) were analysed.

Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia.

Altered parvalbumin (PV) expression is observed in the prefrontal cortex of subjects with schizophrenia. Environmental context, particularly during adolescence, might regulate PV expression. In the present study, we investigated the effect of adolescent social isolation (SI) on PV expression in the medial prefrontal cortex in a neurodevelopmental model (MAM-E17) of schizophrenia.

Adolescent Social Isolation Affects Schizophrenia-Like Behavior in the MAM-E17 Model of Schizophrenia.

Social isolation (SI) during adolescence may induce schizophrenia-like behavior. In the present study, we investigated whether adolescent SI might affect the development of schizophrenia-like behavior in the MAM-E17 neurodevelopmental model of schizophrenia. Rats were socially isolated for 10 days during adolescence (postnatal days (P) 30-40), followed by resocialization until late adolescence (P45-P48) or early adulthood (P70-P75); behavioral and neurochemical studies were performed at these ages.

Adolescent environmental enrichment prevents the emergence of schizophrenia-like abnormalities in a neurodevelopmental model of schizophrenia.

In the present study, we investigated whether exposure to an enriched environment (EE) during adolescence might affect the behavioural dysfunction (sensorimotor gating deficit, memory and social interaction impairments) and neurochemical changes (GAD67 expression, histone methylation) induced by methylazoxymethanol (MAM) in the MAM-E17 rat model of schizophrenia. EE was introduced for 7 days in early adolescence (days 23-29), and behavioural and biochemical studies were performed on adult rats at postnatal day 70. The results showed that exposure to EE prevented the development of adult behavioural deficits induced by prenatal MAM administration.

Fear memory in a neurodevelopmental model of schizophrenia based on the postnatal blockade of NMDA receptors.

Background: Epidemiological data have indicated that memory impairment is observed during adolescence in groups at high risk for schizophrenia and might precede the appearance of schizophrenia symptoms in adulthood.

Methods: In the present study, we used a neurodevelopmental model of schizophrenia based on the postnatal blockade of N-methyl-d-aspartate (NMDA) receptors in rats to investigate fear memory in adolescence and adulthood. The rats were treated with increasing doses of CGP 37849 (CGP), a competitive antagonist of the NMDA receptor (1.

Valproic acid (VPA) reduces sensorimotor gating deficits and HDAC2 overexpression in the MAM animal model of schizophrenia.

Background: Evidence indicates that the disruption of epigenetic processes might play an important role in the development of schizophrenia symptoms. The present study investigated the role of histone acetylation in the development of sensorimotor gating deficits in a neurodevelopmental model of schizophrenia based on prenatal administration of methylazoxymethanol (MAM) at embryonic day 17.

Methods: Valproic acid (VPA), an inhibitor of class I histone deacetylases, was administered (250 mg/kg, twice a day for 7 consecutive days) in early adolescence (23rd-29th day) or early adulthood (63rd-69th day) to rats.

Prenatal MAM administration affects histone H3 methylation in postnatal life in the rat medial prefrontal cortex.

Several findings have indicated that schizophrenia may be connected with the impaired epigenetic regulation of gene transcription. The present study investigated the epigenetic modifications connected with histone H3 methylation at lysine (K)4 and K9 in the medial prefrontal cortex (mPFC) in a neurodevelopmental model of schizophrenia based on prenatal administration of methylazoxymethanol (MAM) at embryonic day 17, which impairs the sensorimotor gating process in adult but not adolescent animals. The effect of MAM was determined at different postnatal ages, pre-puberty (P15, P30 and P45) and post-puberty (P60 and P70), using western blot analyses.