Long-term light and moderate exercise intervention similarly prevent both hippocampal and glycemic dysfunction in presymptomatic type 2 diabetic rats

Abstract

A pre-diabetic population has an increased risk of cognitive decline as well as type 2 diabetes mellitus (T2DM). The present study investigated whether the progression of memory dysfunction and dysregulated brain glycogen metabolism is prevented with four months of exercise intervention from the pre-symptomatic stage in T2DM rat model. Memory function and biochemical and molecular profiles were assessed in the pre-symptomatic stage of OLETF rats, a T2DM model, with LETO rats as genetic control. These rats were subjected to light- or moderate-intensity treadmill running for four months with repetition of the same experiments. Significant hippocampal-dependent memory dysfunction was observed in the pre-symptomatic stage of OLETF rats, accompanied by downregulated levels of hippocampal monocarboxylate transporter 2 (MCT2), a neuronal lactate-transporter, without alteration in hippocampal glycogen levels. Four months of light or moderate exercise from the pre-symptomatic stage of T2DM normalized glycemic parameters and also hippocampal molecular normalization through MCT2, glycogen, and brain-derived neurotrophic factor (BDNF) levels with the improvement of memory dysfunction in OLETF rats. A four-month exercise regimen from the pre-symptomatic stage of T2DM at light and moderate intensities contributed to the prevention of the development of T2DM and the progression of cognitive decline with hippocampal lactate-transport and BDNF improvement.

Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

“…Moreover, miR-382 paired with miR-370 has been confirmed as a sensitive biomarker for the detection of mild cognitive impairment (Salama et al 2020 ). Furthermore, our findings are consistent with previous research that found AE improved cognitive function in diabetic rats and increased expression of BDNF (Jesmin et al 2022 ). In line with our findings, a previous study also unveiled that decreased MALAT1 expression caused by exercise could suppress insulin resistance in T2DM via increasing miR-382-3p expression through synchronous inhibition of resistin (Liu et al 2019 ).…”

The potential mechanisms of lactate in mediating exercise-enhanced cognitive function: a dual role as an energy supply substrate and a signaling molecule

“…Moderate-intensity treadmill running for four weeks resulted in increased glycogen level and MCT2 protein expression in hippocampal tissue as well as an improvement in spatial memory in diabetic rats [ 72 ]. Light and moderate intensity treadmill running for 4 months from the presymptomatic stage in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats (a T2DM model) normalized MCT2, glycogen, and BDNF levels, accompanied by the improvement of hippocampal-dependent memory dysfunction, suggest that exercise can prevent the progression of T2DM-relative cognitive decline by targeting hippocampal lactate-transport [ 73 ]. 8-week swimming exercise significantly increased MCT1, MCT2, and MCT4 protein expression in brain tissue of wild mice and AD mice, accompanied by improvement in learning and memory abilities in the water maze test [ 74 ].…”

Low-Carbohydrate and High-Protein Diet Suppresses Working Memory Function in Healthy Mice

“…There is a possibility that ANLS-related glycometabolism is variable against metabolic conditions. It has been reported that type 2 diabetes induces downregulated MCT2 levels in the rodent hippocampus (24)(25)(26). It is also known that the Western diet, which causes obesity, diminishes central MCT1 and MCT2 levels (27,28); diet-induced metabolic changes could modulate ANLS in the hippocampus.…”