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

Abstract

A second wave of neuronal generation occurs in the ventrobasal nucleus of the rat thalamus (VB) during the first three postnatal weeks. The present study tested the hypotheses (1) that postnatal neurogenesis in the VB is neurotrophin-regulated and (2) that ethanol-induced changes in this proliferation are mediated by neurotrophins. The first studies examined the effects of neurotrophins on the numbers of cycling cells in ex vivo preparations of the VB from three-dayold rats. The proportion of cycling (Ki-67-positive) VB cells was higher in cultured thalamic slices treated with neurotrophins than in controls. Interestingly, this increase occurred with nerve growth factor (NGF) alone or with a combination of NGF and brain-derived neurotrophic factor (BDNF), but not with BDNF alone. Based on these data, the VBs from young offspring of pregnant rats fed an ethanol-containing or an isocaloric non-alcoholic liquid diet were examined between postnatal day (P) 1 and P31. Studies used enzyme-linked immunosorbent assays and immunoblots to explore the effects of ethanol on the expression of neurotrophins, their receptors, and representative signaling proteins. Ethanol altered the expression of neurotrophins and receptors throughout the first postnatal month. Expression of NGF increased, but there was no change in the expression of BDNF. The high affinity receptors (TrkA and TrkB) were unchanged but ethanol decreased expression of the low affinity receptor, p75. One downstream signaling protein, extracellular signal-regulated kinase (ERK), decreased but Akt expression was unchanged. Thus, postnatal cell proliferation in the VB of young rat pups is neurotrophin-responsive and is affected by ethanol.

Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats

“…It has been shown that prenatal and adult chronic EtOH exposure alters levels of neurotrophin, such as brain derived neurotrophic factor (BDNF), in the frontal cortex and hippocampus (Miller et al, 2002; Davis, 2008; Nixon and McClain, 2010; Mooney and Miller, 2011; Vedder et al, 2015). However, few studies have assessed neurotrophin expression after adolescent CIE and the results are variable (Briones and Woods, 2013; McClain et al, 2014; Sakharkar et al, 2016).…”

Dysregulation of TrkB phosphorylation and proBDNF protein in adenylyl cyclase 1 and 8 knockout mice in a model of fetal alcohol spectrum disorder

“…In line with these observations, expression of the mature form of brain-derived neurotrophic factor (BDNF) protein has been demonstrated to be elevated at time points when specific brain regions are less sensitive to the deleterious effects of ethanol, such as the cortex at postnatal day (P) 21 and the striatum at P14 (Heaton, Paiva, Madorsky, Mayer, & Moore, 2003). BDNF protein levels have also been shown to be increased in the hippocampus after neonatal ethanol exposure (Heaton, Mitchell, Paiva, & Walker, 2000), suggesting a protective role for BDNF (Lindvall, Kokaia, Bengzon, Elmér, & Kokaia, 1994) in addition to its role in both synaptic plasticity (Chapleau, Larimore, Theibert, & Pozzo-Miller, 2009) and dendritic development via its receptor, tropomyosin-related kinase B (TrkB), a member of the receptor tyrosine kinase family (Mooney & Miller, 2011; Yacoubian & Lo, 2000). Interestingly, BDNF mRNA does not appear to be present in the striatum of embryonic or neonatal mice (Baquet, Gorski, & Jones, 2004).…”

Sexual dimorphism in BDNF signaling after neonatal hypoxia–ischemia and treatment with necrostatin-1

“…BDNF is greatly expressed in forebrain and diencephalon throughout normal development (Schmidt-Kastner et al, 1996, Lush et al, 2005, Webster et al, 2006). Cortex-derived BDNF is necessary for thalamic axonal outgrowth and target identification (Lotto et al, 2001), but not for thalamic neurogenesis (Mooney and Miller, 2011). The influence of BDNF in remote areas (e.g.…”