Effects of GABAB receptor activation on spatial cognitive function and hippocampal neurones in rat models of type 2 diabetes mellitus

Abstract

The present study was conducted with the aim being to investigate the effect γ-aminobutyric acid type B (GABAB) receptor activation have on spatial cognitive function and hippocampal neurones found in the rat models of type 2 diabetes mellitus (T2DM). T2DM rat models were then established, randomized, and subsequently assigned into normal control (NC), T2DM, T2DM + chemical grade propylene (CGP), T2DM + baclofen, and T2DM + CGP + baclofen groups. T2DM rats’ weight and blood sugar concentrations were monitored. The DMS-2 Morris water maze testing system was performed in order to figure out the spatial cognitive function of these rats. Reverse-transcription quantitative PCR (RT-qPCR) and Western blotting were also performed in order to detect GABAB mRNA and protein expressions. We used the Nissl staining method in order to detect the number of hippocampal neurones, TUNEL (terminal deoxyribonucleotidy transferase-mediated dUTP nick labeling) staining to detect cell apoptosis, and Western blotting method in order to measure the expressions of the apoptosis-related proteins (Bax, cytochrome c (Cyt-c), Caspase-3, and Bcl-2). In comparison with the T2DM group, the weight decreased, blood sugar concentration increased, and spatial cognitive function as well as hippocampal neurones were both impaired in the T2DM + CGP group, contrary to the rats in the T2DM + baclofen group who showed an opposite trend. The situation in the T2DM + CGP + baclofen group was better than that found in the T2DM + CGP group while proving to be more serious than that of the NC and T2DM + baclofen groups. Conclusively, activating the GABAB receptor improved spatial cognitive function and hippocampal neurones in the T2DM rats.

Nicotinate‐curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus

“…Meanwhile, TEM observations showed that CA1 neuronal ultrastructures were impaired in DM rats, manifested by accumulation of APs, damaged mitochondria, and decreased organelles. These findings are in line with previous studies that hippocampal neuronal loss and structure impairment may cause the cognitive deficits in DM animals . Interestingly, our results implied that autophagic flux blockage in the CA1 hippocampus may be responsible for structure damage to this region and impairment of cognitive function in DM rats, which indicated by the evidences that CQ worsened the CA1 injury and cognitive function decline, while RAP ameliorated the CA1 impairment and cognitive function deficits in DM rats.…”

“…Accumulating evidences have confirmed that DM is a major pathogenesis factor for cognitive deficits . Curcumin has been shown to be an effective agent for attenuating diabetic encephalopathy and improving surgery‐induced cognitive dysfunction in mice .…”

“…Accumulating evidences have confirmed that DM is a major pathogenesis factor for cognitive deficits. 4,5,26 Curcumin has been shown to be an effective agent for attenuating diabetic encephalopathy and improving surgery-induced cognitive dysfunction in mice . 17,18,27 In this study, we first explored the effects of the curcumin derivative NC on learning and memory performances of rats with DM induced by STZ.…”

“…Compelling evidence has been indicated that diabetes mellitus (DM) is involved in the pathogenesis of its complications, such as cardiovascular diseases, kidney diseases, and peripheral nerve diseases . Furthermore, studies have revealed the close relationship between DM and cognitive deficits . In addition, animal models with DM exhibit damage to the structure and function of the brain, particularly in the hippocampus, a brain area responsible for learning and memory .…”

Neuroprotective effects of curcumin through autophagy modulation

“…Studies have revealed that diabetes leads to the pathogenesis of other co‐morbidities, such as cardiovascular disease, kidney disease, and peripheral nerve disease . Diabetes has also been associated with increased neuronal damage, particular altered structure and function in the hippocampus, a brain region responsible for learning and memory . Gu et al (2019) assessed the effect of nicotinate‐curcumin, a novel curcumin derivate, on streptozotocin‐induced diabetic rats.…”