Sexual dimorphism modulates metabolic and cognitive alterations under HFD nutrition and chronic stress exposure in mice. Correlation between spatial memory impairment and BDNF mRNA expression in hippocampus and spleen

ANDRÉS PROCHNIK; MARÍA P. MARCONE; ANA M. GENARO; MARA R . RUBINSTEIN; MARÍA R GONZALEZ MURANO; ADRIANA L. BURGUEÑO; MARÍA S. BIANCHI; MIRIAM R WALD

NEUROCHEMISTRY INTERNATIONAL

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2022 vol. 160

0197-0186

Aims: The accumulated evidence suggests that lifestyle - specifically dietary habits andstress exposure - plays a detrimental role in health. The purpose of the present study wasto analyze the interplay of stress, diet, and sex in metabolic and cognitive alterations.Main methods: For this purpose, one-month-old C57Bl/6J mice were fed with a standarddiet or high-fat diet (HFD). After eight weeks, one subgroup of mice from each respectivediet was exposed to 20 weeks of chronic mild stress (CMS), whilst the others were leftundisturbed.Key findings: After 28 weeks of HFD feeding, mice from both sexes were overweight, withan increase in caloric intake and abdominal and subcutaneous fat pads. Stress exposureinduced a decrease in body weight, related to a decrease in caloric efficiency in bothmales and females. Results indicate that males are more susceptible than the females inmodulating metabolic and cognitive functions under HFD and CMS. Although both sexesdemonstrated HFD-induced weight gain, fat accumulation, insulin resistance, highcholesterol, only males exposed to CMS but not females have (i) impaired glucosetolerance with higher glucose level; (ii) significant prolonged latency in Barnes test,suggesting cognitive impairment; (iii) increased IFN-gamma expression in hippocampus,suggesting greater neuroinflammatory response; (iv) poorer cognitive performance relatedto a decrease in hippocampal and spleen BDNF mRNA expression.Significance: The main finding in this study is the presence of a sexual dimorphism inmodulating metabolic and cognitive functions under HFD and CMS, showing males aremore susceptible than females. In addition, poorer cognitive performance was related to adecrease in hippocampal BDNF mRNA expression. Interestingly, these changes wereobserved in the spleen as well.