The features of BECN1 expression in the pyramidal layer of rat hippocampus in chronic cerebral ischemia

Abstract

AbstractBackgroundBECN1 is a member of the Bcl‐2 protein superfamily, belonging to the BH3‐proteins subfamily, which performs many functions, including cross‐regulation of autophagy and apoptosis. BECN1 acts as regulator of the formation and maturation of autophagosomes, the development of neurodegenerative processes in the hippocampus and cerebellum in a BECN1‐knockout mice.MethodChronic cerebral ischemia modeled in rats by limiting cerebral blood flow with applying ligatures to the carotid arteries. The cognitive sphere, the preservation of reflexes, the ability to remember new objects, the degree of neuronal injury, and the level of BECN1 expression in the pyramidal layer of the hippocampus were evaluated. Immunohistochemical study was performed using polyclonal antibodies to BECN1, visualized using diaminobenzidine.ResultThe most pronounced changes were found in the pyramidal layer of the CA1, where neurons with signs of damage were identified along with unchanged neurons. Dystrophic changes in the pyramidal cells were of different severity, determined by a significant increase in the number of hyperchromic neurons, and in most of them total hyperchromia of the nucleus and cytoplasm was observed, a large number of shadow cells were formed. An immunohistochemical study of the hippocampus using antibodies to BECN1 revealed a uniform positive cytoplasmic reaction, mainly of low intensity. A significant increase in expression was found in the CA1, where the relative area of the immunoreactive material increased by 1.1% compared with the control (p <0.001) and reached 1.5%.ConclusionBECN1 is involved in the cross‐regulation of autophagy and apoptosis. According to modern concepts, BECN1 localized intracellularly in the complex with homologs‐proteins of the Bcl‐2 family. With dissociation of the Bcl‐2/BECN1 complex and an increase in free BECN1, autophagy is induced. The observed increase in the expression of BECN1 in CA1 indicates the inclusion of BECN1‐dependent autophagy in this zone in chronic cerebral ischemia.