Alcohol induced depressive-like behavior is associated with a reduction in hippocampal BDNF

Abstract

Strong positive correlation between depression and alcoholism is evident in epidemiological reports. However, a causal relationship for this co-morbidity has not been established. We have observed that chronic daily exposure to a relatively high dose of alcohol can induce depressive-like behavior in rats and that pretreatment with nomifensine or imipramine can block the “depressogenic” effects of alcohol. Since brain derived neurotrophic factor (BDNF) is considered to play an important role in depressive-like behaviors and its elevation, particularly in the hippocampus, appears to be critical for the action of many antidepressants, we hypothesized that: 1. WKY rats, a putative animal model of depression, will show a lower hippocampal BDNF compared to their control Wistar rats, 2. Alcohol-induced depressive like behavior will be associated with a significant decrease in hippocampal BDNF and 3. Treatments with antidepressants will normalize hippocampal BDNF. These postulates were verified by measuring hippocampal BDNF in Wistar and WKY rats at baseline, following chronic (10 day) treatment with alcohol and combination of alcohol with nomifensine or imipramine. Alcohol was administered via inhalation chamber (3 hr/day) such that a blood alcohol level of approximately 150 mg% was achieved. Nomifensine (10 mg/kg) or impiramine (10 mg/kg) were administered i.p daily immediately after alcohol exposure. BDNF was measured by standard Elisa kit. The results support a role for central BDNF in depressogenic effects of alcohol and antidepressant effects of nomifensine and imipramine. Moreover, depression per se as manifested in WKY rats may be associated with a reduction in hippocampal BDNF.

Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects

“…Specifically, in the dentate gyrus, a subpopulation of GABAergic hilar interneurons express NPY, while SGZ NPCs express the Y1 receptor (Sperk et al, 2007). Mice lacking NPY exhibit a significant reduction in cell proliferation while exogenous NPY administration both stimulates cell proliferation and promotes differentiation toward a neuronal phenotype (Hauser et al, 2011; Hensler et al, 2003). Furthermore, modulation of the NPY system could be involved in regulation of alcohol-induced reactive neurogenesis.…”

“…Several rodent studies have shown a similar pattern: chronic alcohol administration reduces BDNF expression in the rat hippocampus, cortex, and hypothalamus (MacLennan et al, 1995; Pandey et al, 1999; TapiaArancibia et al, 2001) whereas BDNF mRNA increases post-withdrawal (Tapia-Arancibia et al, 2001; see also Davis, 2008 for review). Decreases in hippocampal BDNF have also been linked with greater depression-like behavior following alcohol exposure (Briones and Woods, 2013; Hauser et al, 2011). Studies show that administration of antidepressants following alcohol exposure can help mitigate depression-like behavior seen in rodents as well as alcohol-induced effects on some components of adult neurogenesis (Hauser et al, 2011; Stevenson et al, 2009).…”

“…Decreases in hippocampal BDNF have also been linked with greater depression-like behavior following alcohol exposure (Briones and Woods, 2013; Hauser et al, 2011). Studies show that administration of antidepressants following alcohol exposure can help mitigate depression-like behavior seen in rodents as well as alcohol-induced effects on some components of adult neurogenesis (Hauser et al, 2011; Stevenson et al, 2009). Furthermore, an agonist for the BDNF receptor, the tropomyosin-related kinase receptor (trkB), reduced depression-like symptoms associated with alcohol withdrawal/abstinence and also restored neurogenesis during this period (Briones and Woods, 2013).…”

P2X4 Receptor Regulates Alcohol-Induced Responses in Microglia

“…Alcohol is known to cause structural and functional abnormalities to the brain 1-6 including the significant risk associated with chronic alcohol abuse, particularly disorders of the central nervous system (CNS) 7 . Alcohol is known to attenuate phagocytosis 3, 8, 9 , proliferation 4 , expression of neurotrophic factor brain-derived neurotrophic factor (BDNF) in hippocampus 10 and apoptosis in microglia 11 . A hallmark of alcohol-induced neuropathology is activation of microglia 12 .…”

Influence of chronic alcohol treatment on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes in the mouse brain: Role of the C1473G polymorphism in the gene encoding tryptophan hydroxylase 2

“…However, MacLennan et al [30] show that compulsory ethanol consumption for 28 weeks can cause the suppression of Bdnf expression in the hippocampus of Long-Evans rats. A decrease in BDNF level was recorded in the hippocampus of Wistar rats intermittently exposed to ethanol vapor for 10 days [30,50]. However, compulsory ethanol consumption by Wistar rats for 19 weeks did not influence Bdnf expression in the hippocampus [51].…”