BACKGROUND: Perinatal anoxia leads to persistent behavioral and neurochemical alterations suggestive of sensitized dopaminergic function. Because astrocytic basic fibroblast growth factor (bFGF) activity in the midbrain dopaminergic cell body region is required for the development of enduring changes in dopaminergic function induced by stimulant drugs, we investigated the effects of intrauterine anoxia on astrocytic bFGF expression in dopaminergic regions at 2 weeks of age and after a stress manipulation in adults. METHODS: We examined bFGF immunoreactivity in dopaminergic regions of young and adult rats born by cesarean section, cesarean section + 15 min of intrauterine anoxia, or vaginally. bFGF immunoreactivity was also assessed before and after tail-pinch stress in adult animals exposed to the same perinatal interventions. RESULTS: Perinatal anoxia produced persistent decreases in basal bFGF immunoreactivity in the ventral tegmental area (VTA), but enhanced the effect of stress on VTA bFGF immunoreactivity. CONCLUSIONS: Perinatal anoxia has enduring effects on VTA bFGF immunoreactivity and influences adult neuroadaptations to stress. The mechanisms whereby perinatal anoxia alters dopaminergic function may be similar to those responsible for the development of sensitization to stimulant drugs and may involve bFGF.
BACKGROUND: Perinatal anoxia leads to persistent behavioral and neurochemical alterations suggestive of sensitized dopaminergic function. Because astrocytic basic fibroblast growth factor (bFGF) activity in the midbrain dopaminergic cell body region is required for the development of enduring changes in dopaminergic function induced by stimulant drugs, we investigated the effects of intrauterine anoxia on astrocytic bFGF expression in dopaminergic regions at 2 weeks of age and after a stress manipulation in adults. METHODS: We examined bFGF immunoreactivity in dopaminergic regions of young and adult rats born by cesarean section, cesarean section + 15 min of intrauterine anoxia, or vaginally. bFGF immunoreactivity was also assessed before and after tail-pinch stress in adult animals exposed to the same perinatal interventions. RESULTS: Perinatal anoxia produced persistent decreases in basal bFGF immunoreactivity in the ventral tegmental area (VTA), but enhanced the effect of stress on VTA bFGF immunoreactivity. CONCLUSIONS: Perinatal anoxia has enduring effects on VTA bFGF immunoreactivity and influences adult neuroadaptations to stress. The mechanisms whereby perinatal anoxia alters dopaminergic function may be similar to those responsible for the development of sensitization to stimulant drugs and may involve bFGF.
Authors: Natalina Salmaso; Hanna E Stevens; Jessica McNeill; Maha ElSayed; Qiuyin Ren; Maria E Maragnoli; Michael L Schwartz; Simone Tomasi; Robert M Sapolsky; Ronald Duman; Flora M Vaccarino Journal: Biol Psychiatry Date: 2016-03-02 Impact factor: 13.382