Increased apoptosis and reduced neuronal and glial densities in the hippocampus due to nicotine and ethanol exposure in adolescent mice

Abstract

It has been recently shown that nicotine and ethanol interact during adolescence affecting memory/learning and anxiety levels. Considering the role of the hippocampus in both anxiety and memory/learning, we investigated whether adolescent nicotine and/or ethanol administration elicit apoptotic cell death and whether this results in neuronal and/or glial density alterations in the following regions of the hippocampus: granular layer of the dentate gyrus (GrDG), molecular layer (Mol), CA1, CA2 and CA3. From the 30th to the 45th postnatal day, C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50mug/ml in 2% saccharin to drink) and ETOH (25%, 2g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We evaluated cell degeneration (TUNEL assay), neuronal and glial densities (optical disector) and region thicknesses at the end of the period of exposure. Our results demonstrate that ETOH elicited an increase in TUNEL-positive cells relative to the vehicle group in all hippocampal regions. NIC elicited less severe region-dependent effects: the number of TUNEL-positive cells was significantly increased in the Mol and CA1 when compared to the vehicle group. These results were paralleled by reductions in neuronal and glial cells densities, which indicate that both cell types are sensitive to the neurotoxic effects of these drugs. There were no effects on region thicknesses. On the other hand, concomitant NIC and ETOH reduced the adverse effects of the drugs when administered separately. This ability of nicotine and ethanol co-exposure to lessen the adverse effects of nicotine and ethanol may contribute to adolescents co-use and co-abuse of tobacco and alcoholic beverages.

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

“…Although it is still controversial, the potential hazard of ASs has received much attention due to the carcinogenicity (Olney et al, 1996;Reuber, 1978;Weihrauch and Diehl, 2004) and brain damage (Oliveira-da-Silva et al, 2009) of saccharin and aspar tame, respectively. However, there have been no reports to determine the physiologic roles of ASs in serum lipoprotein metabolism.…”

Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl‐2/Bax pathway

“…Lead (Pb) is a common neurotoxicant, and it was found to induce apoptosis in the hippocampus of experimental animals in vivo 25) . Some studies have shown that other neurotoxicants such as CuO, MnCl 2 and ethanol also induced hippocampal neural apoptosis in rats or mice 20,24,26) . These studies indicate that the hippocampus may be a target organ of the neurotoxic agents.…”

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

“…Indeed, a critical role for ethanol in promoting apoptotic events in various cell lines and animal models has been well documented. [20][21][22][23][24][25][26][27][28][29] Also, ethanol stimulates the TRAIL-induced apoptosis in leukemic T-lymphocytes and colon cancer cells in vitro. 38,39 Despite these data, an interactive effect of ethanol and TRAIL in promoting PCa cell death has not been studied.…”

“…[10][11][12][13][14][15][16][17][18][19] Ethanol-induced apoptotic cell death has been well recognized in many cell types and animal models. [20][21][22][23][24] High concentrations of ethanol can effectively destroy hepatoma tumor as well as normal cells, whereas lower concentrations of ethanol selectively induces apoptosis in hepatoma tumor cells but not in normal hepatocytes. 25 Ethanol induces significant apoptosis of purkinje cells in the developing cerebellum.…”