Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats

Abstract

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

The effect of chronic alcohol exposure on spatial memory and BDNF–TrkB- PLCγ1 signaling in the hippocampus of male and female mice

“…In agreement with our results, increased dendritic spine density and neurogenesis in the dentate gyrus and enhancement of hippocampal neuronal arborization were found in alcohol-exposed male rats [ 23 , 46 , 47 ]. Since BDNF plays a potential role in promoting cell proliferation and neurogenesis, these reactive responses are thought to contribute to repair and recovery of the hippocampus of males that showed spatial memory impairment [ 48 , 49 ]. Thus, the upregulation of BDNF-TrkB-PLCγ1 signaling in the hippocampus of males were hypothesized to contribute to recovery after hippocampal damage induced by alcohol.…”

“…In comparison to males, females with alcohol-related cognitive impairment have a slower recovery after 6 weeks of abstinence [ 50 ]. Similarly, increased cell proliferation and immature neurons number were found in female rats on the 14th day of abstinence from alcohol [ 49 ]. These observations indicate that females may suffer from more prolonged memory impairment compared to males and had a slower recovery from alcohol.…”

Light Alcohol Consumption Promotes Early Neurogenesis Following Ischemic Stroke in Adult C57BL/6J Mice

“…Xu et al reported that two-month voluntary alcohol drinking stimulated neurogenesis in the DG and SVZ of male cHAP mice [ 59 ]. Recently, four-day binge drinking was shown to increase hippocampal neurogenesis in adult female Sprague-Dawley rats [ 60 ]. In the present study, although LAC tended to increase both DCX + /BrdU + and NeuN + /BrdU + cells in the DG, the increase did not reach statistically significant levels.…”

Novel Psychopharmacological Herbs Relieve Behavioral Abnormalities and Hippocampal Dysfunctions in an Animal Model of Post-Traumatic Stress Disorder

“…Hilar ectopic DGCs form abnormal neural connections with adjacent DGCs and interfere with hippocampal neural circuits [49,63,64]. Although these cells have been mainly studied in temporal lobe epilepsy, which is characterized by recurrent seizures accompanied by temporarily increased hippocampal neurogenesis, they are also observed in patients with schizophrenia and alcoholism [65][66][67]. In traumatic brain injury, neurons formed after excessive stress such as trauma are localized ectopically to the hilus and molecular layer in the hippocampus [68,69].…”