1 research outputs found
Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity
Objectives Diabetes leads to cognitive impairment and is associated with ageârelated neurodegenerative diseases including Alzheimer's disease ( AD ). Thus, understanding diabetesâinduced alterations in brain function is important for developing early interventions for neurodegeneration. Lowâcapacity runner ( LCR ) rats are obese and manifest metabolic risk factors resembling human âimpaired glucose toleranceâ or metabolic syndrome. We examined hippocampal function in aged LCR rats compared to their highâcapacity runner ( HCR ) rat counterparts. Methods Hippocampal function was examined using proton magnetic resonance spectroscopy and imaging, unbiased stereology analysis, and a Y maze. Changes in the mitochondrial respiratory chain function and levels of hyperphosphorylated tau and mitochondrial transcriptional regulators were examined. Results The levels of glutamate, myo âinositol, taurine, and cholineâcontaining compounds were significantly increased in the aged LCR rats. We observed a significant loss of hippocampal neurons and impaired cognitive function in aged LCR rats. Respiratory chain function and activity were significantly decreased in the aged LCR rats. Hyperphosphorylated tau was accumulated within mitochondria and peroxisome proliferatorâactivated receptorâgamma coactivator 1 α , the NAD + âdependent protein deacetylase sirtuin 1, and mitochondrial transcription factor A were downregulated in the aged LCR rat hippocampus. Interpretation These data provide evidence of a neurodegenerative process in the hippocampus of aged LCR rats, consistent with those seen in agedârelated dementing illnesses such as AD in humans. The metabolic and mitochondrial abnormalities observed in LCR rat hippocampus are similar to wellâdescribed mechanisms that lead to diabetic neuropathy and may provide an important link between cognitive and metabolic dysfunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108300/1/acn386.pd