Evidence map›Paper›PMID 42858201›Full record

ArticlePflugers Archiv : European journal of physiology2026

Treadmill exercise impedes cognitive decline in type 2 diabetic rats by improving mitochondrial function and modulating the TGF-β/Smad-3 pathway.

Dibya Sundar Padhy, Nitish Nirala, Sugato Banerjee

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Article in Pflugers Archiv : European journal of physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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3 authors.

Dibya Sundar PadhyDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India.ORCID http://orcid.org/0000-0002-1540-8223
Nitish NiralaDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India.ORCID http://orcid.org/0009-0001-9496-3312
Sugato BanerjeeDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, India. banerjeesugato1@gmail.com.ORCID http://orcid.org/0000-0002-4402-3066

Funding

Indian Council of Medical Research (ICMR) 5/4/5-11/Diab./20-NCD-III
6 · The paper itself

Abstract

Chronic hyperglycemia and cerebral insulin resistance are the major contributors to cognitive impairment in the ageing population. Due to the increased number of the worldwide type - 2 diabetic mellitus (T2DM) population, the prevalence of cognitive decline and dementia has also increased. It is well documented that moderate aerobic exercise dramatically improves cognitive function in individuals with diabetes. However, the impact of exercise on T2DM-associated cognitive decline modulating TGF-β/Smad-3 signalling is yet to be explored. In this study, we assessed the impact of treadmill exercise on cognitive health in a preclinical model of T2DM, focusing on neuroinflammation, mitochondrial function, and the TGF-β/Smad-3 signalling pathway. To develop an experimental type - 2 diabetic model, rats were fed a high-fat diet (HFD), followed by an intraperitoneal injection of a single low dose of streptozotocin (STZ, 35 mg/kg). After confirmation of diabetes, rats underwent moderate-intensity treadmill exercise for 14 weeks. We observed a significant alternation in behavioural patterns in diabetic rats compared to controls, which reversed on exercise treatment. Moreover, chronic Type - 2 diabetes compromises mitochondrial function and increases inflammation in the hippocampal region of the brain. An increase in pro-inflammatory cytokines, such as IL-1β and TNF-α, was observed in the hippocampus of T2DM animals and was reduced by exercise. Oxidative stress is markedly increased in the type - 2 diabetic brain, resulting in compromised mitochondrial function with elevated hippocampal MDA and decreased GSH and ATP levels, which are reversed in the exercise group. Furthermore, we evaluated the role of exercise on TGF-β/Smad-3 signalling in the type - 2 diabetic brain. Exercise suppresses the overexpression of this signalling cascade in the diabetic brain. In summary, moderate-intensity treadmill exercise ameliorated type - 2 diabetes-associated cognitive impairment by decreasing oxidative stress, neuroinflammation, mitochondrial dysfunction and downregulating the TGF-β/Smad-3 signalling pathway.

Indexed as

Cognitive DysfunctionDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2MitochondriaPhysical Conditioning, AnimalSmad3 ProteinTransforming Growth Factor betaAnimalsMaleOxidative StressRatsRats, Sprague-DawleyRats, WistarSignal TransductionSmad3 ProteinSmad3 protein, ratTransforming Growth Factor betaCognitive impairmentMitochondriaNeuroinflammationTGF-β/Smad-3 pathwayTreadmill exerciseType 2 diabetes mellitus

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.