Environmental Enrichment Alters Neurotrophin Levels After Fetal Alcohol Exposure in Rats

Abstract

Background Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats. Methods Pregnant rats received alcohol by gavage, 0, 4, or 6 g / kg / d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis. Results Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions. Conclusions Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats.

Neurotrophin levels at admission did not change significantly upon alcohol deprivation and were positively correlated with the BMI and LDL levels

“…Prenatal alcohol exposure in rats increased BDNF expression in the frontal cortex, while environmental enrichment resulted, on the contrary, in lowered BDNF [ 17 ]. In mice, the injections of BDNF and NT3 could modulate neuroadaptation to ethanol, potentially influencing the function of postmitotic neurons in the adult brain [ 31 ].…”

“…In another study done on cultured cortical neurons, NT3 treatment did not attenuate the toxic effect of ethanol [ 16 ]. Others found elevated NT3 levels in different brain areas of juvenile rats prenatally exposed to alcohol [ 17 ].…”

Effects of Early Postnatal Exposure to Ethanol on Retinal Ganglion Cell Morphology and Numbers of Neurons in the Dorsolateral Geniculate in Mice

“…Ethanol-induced cell loss has been shown to be caused by apoptotic cell death due to ethanol toxicity (Ikonomidou et al, 2000; Tenkova et al, 2003). Exposure to alcohol during development may also alter neurotrophin levels and/or function (Climent et al, 2002; Heaton et al, 1999: 2000(a); 2000(b); Parks, et al, 2008), and change expression of neurotropic receptors (Dohrman et al, 1997; Light et al, 2002). Neurotrophins and their receptors are important for the survival and differentiation of neurons in the chick retina (Frade et al, 1999).…”

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model

“…These observations are in line with others that already described that EE increases neurogenesis and prevents hippocampal apoptosis (for review, see Hirase andShinohara, 2014 andSale et al, 2014) and it can be related to the improved performance of animals from the EE groups. Although the assessment of the underlying mechanisms of the protective effect of EE is not the aim of the present work, several studies from the literature have pointed to the brain-derived neurotrophic factor (BDNF) as a protective mechanism of EE (Gobbo and O'Mara, 2004;Mattson et al, 2004;Nithianantharajah and Hannan, 2006;Parks et al, 2008;Zhu et al, 2006). Possible mechanisms associated to the beneficial effect of EE, including BDNF, are currently under investigation by our group.…”