Effects of phosphatydilserine administration on neurogenesis, cell proliferation and cell survival in the dentate gyrus of rats submitted to chronic consumption of ethanol

Abstract

Alcoholism is considered a serious public health problem with significant socio-economic impact, according to the WHO (World Health Organization). In addition to the many physical problems, excessive alcohol consumption can lead to severe cognitive and behavioral deficits in both animals and humans. The impairment in hippocampal neurogenesis induced by ethanol consumption can be at least in part related with these cognitive deficits. Phosphatidylserine (PS) is an acid phospholipid and essential component of the cerebral cortex. PS is also the main phospholipid in the structure of brain synaptic membranes and may play an important role in their functioning in nervous impulse transduction, release of secretory vesicles, intercellular communication and changes in glucose, catecholamines and acetylcholinesterase metabolism. These changes in the structure and function of synaptic membranes may be correlated with cognitive and behavioral improvements observed after acute and chronic treatment with PS. Studies have shown that hippocampal neurogenesis may be related to these cognitive and behavioral improvements. Preliminary study in this laboratory showed that acute and chronic administration of PS promoted significant increase in hippocampal cell proliferation and survival. Thus, this study has the objective of analyzing the effects of administration of PS in neurogenesis, cell proliferation and survival in rats submitted to chronic ethanol consumption. Will be used male Wistar rats, 5 months old, kept in cages under controlled conditions (light / dark cycle of 12/12h, 23 ± 2 oC) and food ad libtum. The animals will be submitted to a model of forced consumption of ethanol. The animals will have only access to a bottle containing ethanol solution during the period of 90 days. Preliminary study demonstrated a significant impairment in cell proliferation and survival in animals submitted to this protocol. The animals receive one i.p. injection of BrdU (200 mg/ g) according to the experiment proposed - cell survival or neurogenesis. The experimental group will receive a daily single i.p. injection of PS (50 mg/kg in sterile saline 0.9% in volume 2ml/kg) during the period of 7 days (acute experiment) or 21 days (chronic experiment). The respective control groups will receive only vehicle injections. The object recognition test (episodic memory recognition) will be held six days before perfusion. The animals will be perfused and their brains removed, criosectioned and processed with immunohistochemistry against Ki-67 (cell proliferation), BrdU (cell survival or neurogenesis) and DCX (neurogenesis). One series of sections will be stained with cresyl violet to analyze cell density, hippocampal volume and the number of pycnotic cells (cell in apoptosis) in the dentate gyrus. The present work can have important clinical correlations, since the results obtained can open new perspectives in the treatment of various cognitive and behavioral problems caused by alcoholism. (AU)