Ouabain Reverts CUS-Induced Disruption of the HPA Axis and Avoids Long-Term Spatial Memory Deficits.

Ouabain (OUA) is a cardiotonic steroid that modulates Na+, K+ -ATPase activity. OUA has been identified as an endogenous substance that is present in human plasma, and it has been shown to be associated with the response to acute stress in both animals and humans. Chronic stress is a major aggravating factor in psychiatric disorders, including depression and anxiety. The present work investigates the effects of the intermittent administration of OUA (1.8 µg/kg) during the chronic unpredictable stress (CUS) protocol in a rat's central nervous system (CNS). The results suggest that the intermittent OUA treatment reversed CUS-induced HPA axis hyperactivity through a reduction in (i) glucocorticoids levels, (ii) CRH-CRHR1 expression, and by decreasing neuroinflammation with a reduction in iNOS activity, without interfering with the expression of antioxidant enzymes. These changes in both the hypothalamus and hippocampus may reflect in the rapid extinction of aversive memory. The present data demonstrate the ability of OUA to modulate the HPA axis, as well as to revert CUS-induced long-term spatial memory deficits.

Effects of Physical Exercise on Autophagy and Apoptosis in Aged Brain: Human and Animal Studies.

The aging process is characterized by a series of molecular and cellular changes over the years that could culminate in the deterioration of physiological parameters important to keeping an organism alive and healthy. Physical exercise, defined as planned, structured and repetitive physical activity, has been an important force to alter physiology and brain development during the process of human beings' evolution. Among several aspects of aging, the aim of this review is to discuss the balance between two vital cellular processes such as autophagy and apoptosis, based on the fact that physical exercise as a non-pharmacological strategy seems to rescue the imbalance between autophagy and apoptosis during aging. Therefore, the effects of different types or modalities of physical exercise in humans and animals, and the benefits of each of them on aging, will be discussed as a possible preventive strategy against neuronal death.