Serine racemase expression in the pyramidal layer of the hippocampus of rat in the hypertensive encephalopathy modeling

Abstract

AbstractBackgroundExcessive influence of glutamate on NMDA receptors mediates a cascade of biochemical changes leading to the development of intracellular acidosis, accumulation of free intracellular calcium and activation of a number of enzymes with the formation of free radicals. D‐serine acts as a co‐agonist of NMDA receptors and is involved in learning and memory under normal conditions. However, it has been suggested to play a role in glutamate damage in a number of CNS diseases. The formation of D‐serine in neurons and glial cells occurs with the participation of the enzyme serine racemase (SR) from L‐serine. An increase in the content of SR and the product of its enzymatic reaction, D‐serine, is considered as a process preceding excitotoxicity.MethodHypertensive encephalopathy was modeled on 12‐month‐old rats by the method of exposure to negative longitudinal g‐forces in the caudocranial vector with a force of 9 G for 5 minutes with an interval of 12 hours for 28 days. The following indicators were assessed: behavioral responses, cognitive and mnestic functions, the relative number of neurons with signs of damage, and the level of expression of serine racemase.ResultA morphometric study of the pyramidal layer of the hippocampus revealed a significant increase in the relative area of the immunopositive material in CA1 by 5.5% compared with the control (p<0.05). A feature of the expression of serine racemase in the experimental group was the translocation of immunopositive material, which was determined not only in the cytoplasm of perikaryons, but also in the dendrites of pyramidal neurons. In addition, the nature of expression changed in the experimental group to a moderately pronounced one, and in some pyramidal neurons to a pronounced one. Violation of the cytoarchitectonic of the CA1 zone was manifested in a less compact arrangement of pyramidal neurons, a pattern of spongiosis due to pericellular and perivascular edema, and the acquisition of increased tortuosity by neuronal dendrites.ConclusionHypertensive encephalopathy modeling demonstrates a sharp increase in the relative number of neurons with signs of damage, a decrease in the specific