Testosterone deprivation intensifies cognitive decline in obese male rats via glial hyperactivity, increased oxidative stress, and apoptosis in both hippocampus and cortex

Abstract

Aim:The study hypothesized that testosterone deprivation aggravates cognitive decline in obesity through increasing oxidative stress, glial activation, and apoptosis. Methods: Male Wistar rats (n = 24) were fed with either normal-diet (ND) or high-fat diet (HFD) for 24 weeks. At week 13, ND-fed rats and HFD-fed rats were randomly assigned to two subgroups to receive either a sham-operation or bilateral-orchiectomy (ORX). Rats were evaluated for metabolic parameters and cognition at 4, 8, and 12 weeks after the operation. At the end of protocol, the reactive oxygen species (ROS), glial morphology, and cell apoptosis were determined in hippocampus and cortex. Results: Both HFD-fed groups developed obese-insulin resistance, but ND-fed rats did not. HFD-fed rats with sham-operation showed cognitive decline, when compared to ND-fed rats with sham-operation at all time points. At 4-and 8-week after ORX, the cognitive impairment of ND-fed rats and both HFD-fed groups was not different. However, 12-week after ORX, cognitive decline and of glial hyperactivity of HFD-fed rats had the greatest increase among all groups. Hippocampal ROS levels and apoptotic cells in both HFD-fed groups were equally increased, but the cortical ROS levels and apoptotic cells of HFD-fed rats with ORX were the highest ones. Conclusions: These findings suggest that testosterone deprivation aggravates cognitive decline in obesity via increasing oxidative stress, glial activity and apoptosis. K E Y W O R D Sapoptosis, cognitive function, glia function, obesity, reactive oxygen species, testosterone deprivation

The effects of feeding obese rats with bee bread on leptin and ghrelin expression

“…In an investigation carried out by Sa-nguanmoo et al (2018), it was detected that obesity insulin resistance developed with an increase in systemic inflammation, brain mitochondrial dysfunction, rise in brain apoptosis, and disruption and cognitive reduction in hippocampal plasticity in rats fed a high-fat diet. Chunchai et al (2018) indicated that long-term high-fat diet consumption induced metabolic disruption, cognitive disruption, glial morphological changes, increased hippocampal oxidative stress, and cell apoptosis in both the hippocampus and cortex, and obesity. When assessing the apoptosis results of our study, it was witnessed that it was effective in the groups to which bee bread was given upon statistically increasing apoptosis in the obese groups compared to both the control and metformin groups.…”

Adipose tissue—more than just fat

“…It has become clear that in obesity not only adipose tissue itself is affected. The research of Chunchai et al focuses on the relation between obesity and metabolic and inflammatory brain pathologies. Their recent study monitors the influence of testosterone on obesity‐induced metabolic disturbance, cognitive function as determined by the Morris Water maze test, glial morphological changes, increased hippocampal oxidative stress and cell apoptosis in hippocampus and cortex in rats.…”

“…Interestingly, under high fat diet a cognitive decline in obesity was aggravated by testosterone deprivation. The underlying mechanism might be related to oxidative stress and glial apoptosis …”

“…A number of articles addressing basic mechanisms related to obesity have recently appeared in Acta physiologica. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] One area of clinical relevance for obese patients is the immune system. Duan et al 20 recapitulate the connections between a high-fat diet and diseases.…”

“…The underlying mechanism might be related to oxidative stress and glial apoptosis. 4 Behaviour, influencing food intake as well as physical activity, is a key determinant in the development of obesity. The arcuate nucleus in the hypothalamus, together with anorexigenic POMC (pro-opiomelanocortin) neurons are key players in appetite suppression.…”