A major pathogenic mechanism of chronic alcoholism involves oxidative burden to liver and other cell types. We show that adult neurogenesis within the dentate gyrus of the hippocampus is selectively impaired in a rat model of alcoholism, and that it can be completely prevented by the antioxidant ebselen. Rats fed for 6 weeks with a liquid diet containing moderate doses of ethanol had a 66.3% decrease in the number of new neurons and a 227-279% increase in cell death in the dentate gyrus as compared with paired controls. Neurogenesis within the olfactory bulb was not affected by alcohol. Our studies indicate that alcohol abuse, even for a short duration, results in the death of newly formed neurons within the adult brain and that the underlying mechanism is related to oxidative or nitrosative stress. Moreover, these findings suggest that the impaired neurogenesis may be a mechanism mediating cognitive deficits observed in alcoholism.A lcohol dependence and abuse are among the most prevalent mental disorders in the United States, with Ϸ14% of the general population meeting criteria for alcohol dependence at some time in their lives and 7% having been dependent in the past year (1). Severe cognitive impairment consistently occurs in chronic alcoholism regardless of the presence of associated thiamine deficits (Korsakoff syndrome), and it includes progressive and severe anterograde learning deficits, implicating impairment in hippocampal circuits. However, no consistent pathological finding has yet been identified. The neuropathological correlate of the cognitive impairments accompanying alcoholism remains unclear (2-4). In animal models of alcoholism, a thinning of the granular layer of the dentate gyrus (DG) is attributed to neuronal loss (5). These findings, however, have been difficult to confirm in human brains (6) and have been contested in animal models as well (7). Human postmortem studies account for the duration of alcohol abuse but not the duration of abstinence before death. Interestingly, MRI studies demonstrate reduction of hippocampal volumes in alcoholics that are reversible after short periods of abstinence (8). The loss of hippocampal volume has been attributed to changes in white matter (6), but the incorporation of newly formed neurons to the DG could also be affected by alcohol. Similarly, hippocampaldependent cognitive functions have also shown reversibility after comparable periods of abstinence.Neurogenesis is primarily a developmental process that involves the proliferation, migration, and differentiation into neurons of primordial CNS stem cells (9, 10). Neurogenesis declines until it ceases in the young adult mammalian brain with two exceptions: the olfactory bulb (OB) and the hippocampus produce new neurons throughout adult life. In the subgranular cell layer of the DG, hippocampal progenitors proliferate and migrate a short distance into the granule cell layer, where they differentiate into hippocampal granule cells. Although multiple factors seem to regulate adult neurogenesis including...

The increased levels of oxidative stress markers and the decreased antioxidant capacity and antioxidant defenses in KC corneas, as well as in the post-LASIK ectatic corneas, indicate that oxidative stress might be involved in the development of this disease and may provide new insights for its prevention and treatment in the future.

Lutein and DHA are capable of normalizing all the diabetes-induced biochemical, histological, and functional modifications. Specifically, the cell death mechanisms involved deserve further studies to allow the proposal as potential adjuvant therapies to help prevent vision loss in diabetic patients.

The aim of this study was to test the effect of lipoic acid treatment on the retina after a short diabetic insult. Diabetes was induced by alloxan and mice were divided into sub-groups; control, diabetic, diabetic+insulin and all groups received+/-lipoic acid (100 mg/kg body weight) for 3 weeks. GSH content, MDA concentration, GPx activity were measured and electroretinograms (ERG) were recorded. Early administration of lipoic acid to diabetic mice prevented the statistically significant decreases of GSH content and GPx activity and normalized MDA concentration. Moreover, lipoic acid restored electroretinogram b-wave amplitude of diabetic animals to control values. Lipoic acid has a protective effect on the diabetic retina.

The results herein strongly suggest that oxidative mechanisms may underlie the hippocampal effects of ethanol in adult rats, in view of the protective effect of ebselen.