Genistein attenuates cognitive deficits and neuroapoptosis in hippocampus induced by ketamine exposure in neonatal rats

Abstract

Ketamine is a frequently used anesthetic in pediatric patients that can cause cognitive impairment. Genistein, a bioactive component of soy products, has been shown to suppress neuronal death through regulating the expression of apoptosis related genes. In this study, we hypothesized that genistein could alleviate ketamine‐induced cognitive impairment by ameliorating hippocampal neuronal loss and tested this hypothesis in rats. Neonatal rats were treated with ketamine and genistein. Hippocampal tissue was harvested for histological and biochemical analysis to determine neuronal apoptosis and proteins involved in the apoptotic pathways. Behavioral assays including contextual fear conditioning test and Morris water maze test were performed to assess cognitive functions, including learning and memory. We found that in fear conditioning test, genistein restored freezing time in ketamine treated rats in a dose dependent manner. Similarly, genistein attenuated impaired learning and memory in Morris water maze test in rats treated with ketamine. Additionally, ketamine‐induced neuronal apoptosis in rat hippocampus was attenuated by genistein treatment. Finally, we found that genistein partially restored proteins associated with apoptosis, including Bax, Bcl‐2, cleaved caspase 3, and phosphorylated GSK‐3ß and Akt. Genistein suppresses hippocampal neuronal loss and cognitive disruption induced by ketamine in rats.

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

“…Along the same lines of research, KET administration from 42 to 47 postnatal days, resulted in a decrease of cell proliferation in the subventricular and subgranular zone, inhibited neural stem cells proliferation and neuronal differentiation, promoted neural stem cells apoptosis, and increased cleaved caspase-3 , neurophysiological events linked to the decline of the acquisition and evocation of spatial memory in the MWM. Finally, the injection of this agent in the neonatal stage produced cognitive impairment in the MWM, together with neuronal death by apoptosis in the Hp, and decreased expression of proteins such as Bax, Bcl-2, cleaved caspase 3, and phosphorylated GSK-3ß and Akt (Li and Zhang, 2021).…”

Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases

“…Notably, genistein has shown promising properties in reducing cognitive deficits and neuronal loss in rats administered with ketamine to induce neurodegeneration. These effects were achieved through the regulation of apoptosis-related genes such as those encoding Bax, Bcl-2, caspace 3, and phosphorylated GSK-3b and Akt [ 187 ]. Genistein can inhibit the activity of NF-κB signaling pathway, which can be activated via TLR4 and which is one of the important elements influencing the development of neurodegenerative disease.…”