Temporally Specific Burst in Cell Proliferation Increases Hippocampal Neurogenesis in Protracted Abstinence from Alcohol

Abstract

Adult neurogenesis is a newly considered form of plasticity that could contribute to brain dysfunction in psychiatric disease. Chronic alcoholism, a disease affecting over 8% of the adult population, produces cognitive impairments and decreased brain volumes, both of which are partially reversed during abstinence. Clinical data and animal models implicate the hippocampus, a region important in learning and memory. In a model of alcohol dependence (chronic binge exposure for 4 d), we show that adult neurogenesis is inhibited during dependence with a pronounced increase in new hippocampal neuron formation after weeks of abstinence. This increase is attributable to a temporally and regionally specific fourfold increase in cell proliferation at day 7 of abstinence, with a majority of those cells surviving and differentiating at percentages similar to controls, effects that doubled the formation of new neurons. Although increases in cell proliferation correlated with alcohol withdrawal severity, proliferation remained increased when diazepam (10 mg/kg) was used to reduce withdrawal severity. Indeed, those animals with little withdrawal activity still show a twofold burst in cell proliferation at day 7 of abstinence. Thus, alcohol dependence and recovery from dependence continues to alter hippocampal plasticity during abstinence. Because neurogenesis may contribute to hippocampal function and/or learning, memory, and mood, compensatory neurogenesis and the return of normal neurogenesis may also have an impact on hippocampal structure and function. For the first time, these data provide a neurobiological mechanism that may underlie the return of human cognitive function and brain volume associated with recovery from addiction.

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

“…A compensatory burst in cell proliferation also occurs after alcohol abstinence. 54 In addition, the damaged SVZ subsequent to antimitotic exposure is capable of completely regenerating itself from stem cells after 10 days of antimitotic withdrawal. 55 It is possible that cell proliferation in the SGZ of hypothyroid animals becomes more sensitive to TH treatment, so that even slightly increased TH levels in the treated animals could result in a significant upregulation of proliferation.…”

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

“…The effect of drugs of abuse on neurogenesis seems to be selective for the SGZ, and does not seem to occur in the SVZ (Nixon and Crews, 2004). A decrease in hippocampal neurogenesis may result in long-lasting effects on learning, memory and cognition.…”

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

“…Triple-label confocal microscopy was performed according to Nixon and Crews (2004). The colocalization of BrdU with neuronal-specific nuclear protein (NeuN) or glial fibrillary acidic protein (GFAP) proteins was used to characterize the fate of surviving NPCs.…”