Ascorbic Acid Supplementation Attenuates Hippocampal Neuronal Damage in Orchiectomized Rats

Abstract

Understanding the bidirectional relationship in the cellular and molecular mechanisms associated with testosterone deprivation and cognitive activities has become a high-priority goal. Testosterone has been shown to have effects in the nervous system, ranging from targeting gene expression to modulating neurotransmission. This study therefore evaluated the modulatory role of ascorbic acid in the hippocampus of orchiectomized rats. Twenty-one adult male Wistar rats with an average weight of 170g±10g were randomly assigned into three groups of seven rats each; the control, orchiectomized (orchiectomy+flutamide, 11 mg/kg body weight, bw), and ascorbic acid (orchiectomy+flutamide, 11 mg/kg bw + ascorbic acid, 100 mg/kg bw). Treatment was by oral gavage and lasted for 30 days. Nitrosative stress and neuroinflammatory analysis, hormonal, histological and immunohistochemical expression of astrocytes in the hippocampus were examined. Results showed significantly increased expression of acetylcholinesterase, inducible nitric oxide synthase, and tumour necrotic factor-alpha in the hippocampus of orchiectomized animals. There was altered cytoarchitectural morphology evidenced by reduced Nissl profiles in neuronal axons and dendrites, which corresponded to apoptotic changes, and increased expression of reactive astrocytes suggesting neuronal damage. Nitrosative stress and inflammatory perturbations were well modulated in animals treated with ascorbic acid with unaltered hippocampal morphology. The results indicated that decline in brain androgen activities caused inflammatory and oxidative stress-driven alterations in the hippocampus, while ascorbic acid supplementation offered therapeutic value by modulating neurochemicals and scavenging free radicals in the hippocampus.