Nerve growth factor neuroprotection of ethanol-induced neuronal death in rat cerebral cortex is age dependent

Abstract

Organotypic cultures of rat cortex were used to test the hypotheses that nerve growth factor (NGF) is neuroprotective for immature cortical neurons and that ethanol abolishes this neuroprotection in a developmental stage-dependent manner. Samples were obtained on gestational day (G) 16 or postnatal day (P) 3 and cultured with ethanol (0 or 400 mg/dl) and NGF (0 or 30 ng/ml) for 72 hours. Dying neurons were identified as exhibiting terminal nick-end labeling, immunoreactivity for activated caspase 3, or condensed nuclear chromatin. Two cortical compartments were examined in fetal tissue; a superficial, cell-sparse marginal zone (MZ) and a cell-dense cortical plate (CP). At P3, the CP was subdivided into a cell-dense upper cortical plate (UCP) and a less densely packed lower cortical plate (LCP). Neuronal death in the MZ was affected by neither NGF nor ethanol at both ages. In the fetal CP, NGF did not affect the incidence of cell death, but ethanol increased it. Treatment with NGF caused an upregulation of the expression of Neg, a gene known to be affected by NGF and ethanol. NGF did not ameliorate the ethanol-induced death. In pups, ethanol increased the amount of death in the LCP. NGF did protect against this death. Neither ethanol nor NGF altered the incidence of cell death in the UCP. The laminar-dependent neuroprotection did not correlate with expression of NGF receptors or Neg. Thus, NGF can be protective against the neurotoxic effect of ethanol in the neonatal brain. This effect is site-selective and time-dependent and it targets post-migratory, differentiating neurons. Keywordsfetal alcohol syndrome; ethanol; neurotrophin; apoptosis; p75; trk Naturally occurring neuronal death (NOND) in the developing mammalian CNS is a wellorchestrated phenomenon. Neurons are overproduced and then a portion of them dies

Effects of minocycline on the expression of NGF and HSP70 and its neuroprotection role following intracerebral hemorrhage in rats

“…The binding of NGF to TrkA results in receptor phosphorylation, followed by the activation of signaling pathways that enhance cell survival and neuronal differentiation. In contrast, signaling via p75NTR can activate pathways of cell death[20]. Therefore, the final effect of NGF is a balance between cell survival signal derived from the TrkA family and cell death signal from the p75NTR[21].…”

Role of neurotrophins on postnatal neurogenesis in the thalamus: prenatal exposure to ethanol

“…Three-day-old Long-Evans rat pups from dams fed chow and water ad libitum were used for generating organotypic slice cultures (Mooney and Miller, 2003; 2007a). Animals were anesthetized (100 mg/kg ketamine and 10 mg/kg xylazine) and decapitated.…”

The Proapoptotic BH3-Only, Bcl-2 Family Member, Puma Is Critical for Acute Ethanol-Induced Neuronal Apoptosis

“…Ethanol may have differential effects on immature neurons; it may act as a stimulant on them, rather than as a generalized CNS depressant (9). Extensive studies have shown that neurons develop resistance to the effects of ethanol as they mature (10, 11). Other reports have shown that administration of doses of ethanol that would cause extensive neuronal loss in neonatal mice are not associated with loss of neurons in the adult brain (12, 13).…”