Endurance training mitigates obesity-induced hippocampal impairment by enhancing neurotrophin signalling, synaptic plasticity, and cellular responses in a female rat model

TL;DR

Endurance training helps reduce obesity-related brain damage in female rats by boosting brain growth factors and improving memory.

Contribution

The study reveals how endurance training alters specific brain pathways to counteract obesity-induced hippocampal damage in female rats.

Findings

Endurance training increased BDNF and TrkB mRNA levels in the hippocampus.

Trained obese rats showed improved synaptic plasticity and memory in behavioral tests.

ET reduced inflammation and promoted brain cell regeneration in obese rats.

Abstract

Obesity-related health issues, including cognitive decline linked to hippocampal neurogenesis and neuroplasticity, are gaining more attention as obesity rates rise worldwide. Physical activity is recognized as a potent stimulator of neurotrophic factors. This study examined the impact of six weeks of treadmill training on hippocampal molecular pathways in adult female Zucker diabetic fatty (obese) and Zucker lean rats. Animals were assigned to either treadmill exercise (n = 10) or sedentary control (n = 10) groups. Endurance training (ET) markedly upregulated mRNA expression of brain-derived neurotrophic factor and its receptor. The PI3K/Akt pathway was upregulated only in the trained lean rats and downregulated in the trained obese group compared with sedentary controls. ET elicited divergent effects on neurotrophin-associated PLCγ/PKC/CAMKII signalling between lean and obese groups. Sedentary obese rats primarily utilized the PLCγ/PKC axis, while both trained groups (lean and obese) showed increased CAMKII expression, associated with enhanced synaptic plasticity and memory. Enhanced synaptophysin mRNA indicated improved synaptogenesis and plasticity following ET. Trained obese rats also exhibited reduced expression of the microglial pro-inflammatory marker Iba1, alongside increased markers of oligodendrocyte regeneration and neurofilament expression. Behavioral assessment via the passive avoidance test demonstrated improved learning and memory in trained obese animals. Collectively, these findings suggest that ET may mitigate obesity-induced hippocampal damage, exert neuroprotection, and enhance hippocampal function.

Endurance training is a potent modulator of gene expression changes in the hippocampus. Changes are reflected in the expression profile of neurotrophic factors and their receptors, genes involved in neurotrophic factors signaling, synaptic markers, or regeneration parameters.

Endurance training is a potent modulator of gene expression changes in the hippocampus. Changes are reflected in the expression profile of neurotrophic factors and their receptors, genes involved in neurotrophic factors signaling, synaptic markers, or regeneration parameters.

•6-week endurance training (ET) enhanced hippocampal mRNA levels of BDNF/TrkB.•ET increased regeneration-related transcripts CNP, PLP1, and NF-l in obese rats.•ET upregulated CAMKII and synaptophysin mRNAs, supporting plasticity and memory.•The passive avoidance test showed improvement in learning and memory in obese rats.

6-week endurance training (ET) enhanced hippocampal mRNA levels of BDNF/TrkB.

ET increased regeneration-related transcripts CNP, PLP1, and NF-l in obese rats.

ET upregulated CAMKII and synaptophysin mRNAs, supporting plasticity and memory.

The passive avoidance test showed improvement in learning and memory in obese rats.

Figures