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Exercise Mitigates Cognitive Functions through Mitochondrial Remodeling in Type‐2 Diabetes
Author(s) -
Kalani Anuradha,
Chaturvedi Pankaj,
Winchester Lee J,
Tyagi Suresh C,
Tyagi Neetu
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1014.2
Subject(s) - type 2 diabetes , endocrinology , medicine , diabetes mellitus , leptin , cognition , mitochondrion , effects of sleep deprivation on cognitive performance , obesity , biology , psychiatry , microbiology and biotechnology
Abnormal brain mitochondrial functions result in cognitive impairments during type‐2 diabetes (T2D). Exercise has been recommended by clinicians to diabetics as a secondary protective therapy; however, its effect on alleviating brain functions through mitochondrial interventions is not much explored. Therefore, we hypothesize that exercise mitigates T2D‐induced neurodegeneration and cognitive functions through mitochondrial remodeling. To test this hypothesis, we used obese diabetic db/db (leptin receptor knockout) and db/+ mice as controls, with and without exercise. The mice were exercised at a constant speed of 7 meters/min for 5 days a week/total 8 weeks. Diabetic mice with exercise had reduced total body weight (R 2 =0.9154, F=72.15, p<0.001), blood glucose (R 2 = 0.9264, F=83.92, p<0.001), liver weight (R 2 =0.9703, F=217.6, p<0.001) and improved heart weight (R 2 =0.7572, F=20.79, p<0.001) as compared to other experimental groups. However, no significant differences were observed in the weight of kidney, brain, and lungs. We next assessed cognitive and behavior alterations by open field, novel object recognition, Y‐maze, and hot plate analgesia tests. Our results suggest significant improvement in behavior and cognitive functions after exercising diabetic db/db mice as compared to non‐exercised db/db and control littermates. Results with RT 2 profiler PCR array, designed especially for mitochondrial genes, confirmed improvements in mitochondrial transport, dynamics, and regulatory genes in exercised db/db brain as compared to non‐exercised db/db brains. The involvement of mitochondrial remodeling in db/db mice following exercise was further confirmed by significant increase in ATP production, membrane potential, copy number as well as decrease in reactive oxygen species when compared with non‐exercised db/db and control mice. Furthermore, considerable reduction in TUNEL reactivity was determined in intact mitochondria isolated from exercised db/db mice as compared to non‐exercised and control mice. In addition, the effect of exercise on neuronal survival in diabetic brain was confirmed by decrease in fluoro‐jade C reactivity that particularly stains degenerating neurons. Taken together, our results indicate myriad beneficiary effects of exercise over metabolic and mitochondrial pathology in diabetes. Furthermore, our findings suggest regular exercise mitigate neurodegeneration and cognitive disorders thereby improving total mitochondrial health. Support or Funding Information This work was supported by NIH grant HL107640‐NT.