Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring

Abstract

Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75 NTR , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75 NTR in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

Serum BDNF and NGF Modulation by Olive Polyphenols in Alcoholics during Withdrawal

“…The most commonly known effects on neurotrophins of chronic alcohol addiction are disrupted nerve outgrowth, impaired neuronal survival, limited ability to promote neuronal regeneration, and alterations in the neurochemical phenotypes of selected neuronal cell lines [22,43]. Furthermore BDNF and NGF expressions are also known to be affected by ethanol exposure in fetus or by paternal alcohol consumption [2,21]. Thus, circulating BDNF and/or NGF alteration could have a critical role in chronic alcohol-induced neurotoxicity.…”

“…Firstly, it cannot be excluded the possibility that peripheral changes in BDNF/NGF in alcoholics could reflect changes in BDNF/NGF in the brain including those associated with polyphenols supplementations since i: intracerebroventricular neurotrophins injections can influence the physiology of peripheral cells [53]; ii: under certain pathophysiological conditions neurotrophins can cross the blood-brain barrier [54,55]. iii: chronic, acute or prenatal alcohol exposure is known to affect brain BDNF and/or NGF in several brain areas [2,10,21,28,56]. Secondly, alcoholics of our samples were smokers with also a long history of smoking and nicotine is known to affect the expression of both BDNF and NGF [57,58] including, then, the possibility that nicotine-use history in alcoholics may have contributed to the present data.…”

“…NGF and BDNF were measured following indications previously released (2) in the blood serum of the subjects. NGF/BDNF evaluation was carried out with ELISA kits ''NGF EmaxTM ImmunoAssay System number G7631'' and ''BDNF EmaxTM ImmunoAssay System number G7611'' by Promega (Madison, WI, USA) following the instructions provided by the manufacturer.…”

“…Prolonged alcohol consumption and withdrawal following chronic or prenatal [1,2] alcohol intake causes various kinds of tissue damage; this results from increased cell death or decreased cell proliferation in several regions of the brain and other target organs of ethanol intoxication [3][4][5][6]. Several anatomical studies of the alcoholic brain show that changes in the hippocampus, extrahippocampal cortex, and basal forebrain can induce memory dysfunction [7] and learning disabilities [8].…”

“…Although the mechanisms having a role in chronic alcohol treatment-induced neurotoxic actions have not yet been clearly identified, different investigations have hypothesized that alcohol intake (i.e. acute, chronic, during gestation, paternal [1,2,9,10]) may disrupt the synthesis of neurotrophins, which are a proteins' family playing a crucial role in cognitive function, including the processes of learning and memory [11,12]. Neurotrophins are particularly important in many aspects of brain cells' development, nutrition, growth and survival [12][13][14].…”