Localised streptozotocin-induced structural and cognitive changes in the hippocampal cornu ammonis 1 (CA-1) neurons and mitigating effects of Zingiber officinale

Abstract

BackgroundThe study was done to establish the neurotoxic effect of intracerebroventricular streptozotocin (ICV STZ)-induced brain insulin resistance, and also considered Zingiber officinale (Z. officinale) mechanism of action in ameliorating behavioural, molecular and histopathological changes associated with ICV STZ-induced brain insulin resistance in Wistar rat model. Method32 male Wistar rats weighing between 160 and 200 g were grouped into 4 (n = 8) labelled A-D and housed in standard seized home plastic cages at 23 ± 1 °C. Group-A (control) received a single ICV injection of normal saline, Group-B received 300 mg/kg of Z. officinale, Group-C received single dose of ICV STZ at 3 mg/kg and Group-D received single dose of ICV STZ at 3 mg/kg with 300 mg/kg/ of Z. officinale. Administration of Z. officinale extract was done orally and for 21 consecutive days. Values were represented in graphs and table, and analysed using GraphPad Prism 6.0 software. ResultsOrgan weight revealed a drastic loss, which was not significant following 3 mg/kg of ICV STZ. Also, ICV STZ significant reduced and increased rat performance in open arm entry (OAE) and closed arm duration (CAD) respectively, with an obvious insignificant reduction of rat spontaneous alterations (SA) performance as well as the relative expression of insulin receptor substrate (IRS) gene in the brain when compared with control and other groups. The relative expression of Beta-secretase 1 (BACE-1) and glycogen synthase kinase 3-beta (GSK 3β) gene significantly increased in ICV STZ treated rats. Furthermore, photomicrographs revealed scattered layers of pyramidal cells, with chromatolysed and degenerating neurons in the cornu ammonis 1 (CA-1) region of the hippocampus. Similarly, accumulation of amyloid-beta was seen in the CA-1 region, which correlates the loss of neuronal cells and neurobehavioural deficit. ConclusionHowever, Z. officinale was capable of mitigating this effect by enhancing the antioxidant defense system, which possibly inhibited the activities of free radical or reactive oxygen generation and subsequently suppressed GSK 3β and BACE-1 gene expression.