Efeitos da administração intrahipocampal de 2-APB na memória espacial e na ansiedade de ratos submetidos à anóxia neonatal

Abstract

The neonatal anoxia (oxygen deprivation at birth) is the leading cause of brain injury in newborns and presents high morbidity and mortality rates, especially in preterm infants. Reductions in oxygen supply in the developing brain can lead to alterations and even cell death in susceptible structures such as the hippocampus, a key structure in regulating learning and memory. Deficits in learning and memory, among others, are frequent sequelae of neonatal anoxia. In addition to these functions, recent studies indicate that while the dorsal portion of the dentate gyrus has a predominant role in spatial memory and learning, the ventral portion thereof is associated with anxiety. These consequences may result from several cascades triggered by lack of oxygen, among which those triggered by changes in intracellular calcium levels. During oxygen deprivation, an increase in the concentration of calcium ions within the cell and organelle such as mitochondria and endoplasmic reticulum, causing changes in their membranes and causing the release of pro-apoptotic proteins in the cytosol. The calcium ions are mainly stored in the endoplasmic reticulum and function as second messengers in many biological processes. The increase in intracellular calcium signaling can interfere with several regulatory functions, affecting synaptic plasticity and neuronal excitability, and can even lead to cell death. The intracellular calcium receptors inositol 1,4,5-triphosphate (IP3R) are responsible for the maintenance of intracellular ion concentration. Few studies show the role of intracellular calcium receptors in response to oxygen deprivation and there are no studies about the IP3R after neonatal anoxia in brain tissue much less correlation with the observed behavioral deficits noo this animal model of neonatal anoxia. The use of IP3R blockers, such as 2-Aminoethoxydiphenyl borate (2-APB), appears to be an ideal tool for the study of the influence of the IP3R hippocampal cell death and in this structure functions as a spatial memory and anxiety. A better understanding about the calcium release mechanisms against the anoxic insult and its amendments is of paramount importance for the development of therapeutic approaches that minimize the damage caused by oxygen deprivation and their functional consequences. Thus, this project aims to verify that the intrahippocampal injection 2-APB alters the pattern of cell death in the hippocampus of rats 24 hours after being submitted to neonatal anoxia and analyze the possible influence of intrahippocampal injection 2-APB on behavioral changes (spatial memory and anxiety) in adult rats that underwent neonatal anoxia.