Theology, News and Notes - Vol. 13, No. 03

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1026/thumbnail.jp

Theology, News and Notes - Vol. 30, No. 04

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1083/thumbnail.jp

Theology, News and Notes - Vol. 16, No. 04

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1194/thumbnail.jp

Theology, News and Notes - Vol. 47, No. 01

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1139/thumbnail.jp

Theology, News and Notes - Vol. 13, No. 01

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1190/thumbnail.jp

mGluR2/3 activation of the SIRT1 axis preserves mitochondrial function in diabetic neuropathy

ObjectivesThere is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function.MethodsAdult male streptozotocin treated Spragueâ Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268. Neuropathy end points included mechanical allodynia, nerve conduction velocities (NCV), and intraepidermal nerve fiber density (IENFD). Markers of oxidative stress, antioxidant response, glutamate recycling pathways, and mitochondrial oxidative phosphorylation (OXPHOS) associated proteins were measured in dorsal root ganglia (DRG).ResultsIn diabetic rats, NCV and IENFD were decreased. Diabetic rats treated with an mGluR2/3 agonist did not develop neuropathy despite remaining diabetic. Diabetic DRG showed increased levels of oxidized proteins, decreased levels of glutathione, decreased levels of mitochondrial DNA (mtDNA) and OXPHOS proteins. In addition, there was a 20â fold increase in levels of glial fibrillary acidic protein (GFAP) and the levels of glutamine synthetase and glutamate transporter proteins were decreased. When treated with a specific mGluR2/3 agonist, levels of glutathione, GFAP and oxidized proteins were normalized and levels of superoxide dismutase 2 (SOD2), SIRT1, PGCâ 1α, TFAM, glutamate transporter proteins, and glutamine synthetase were increased in DRG neurons.InterpretationActivation of glutamate recycling pathways protects diabetic DRG and this is associated with activation of the SIRT1â PGCâ 1αâ TFAM axis and preservation of mitochondrial OXPHOS function.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142324/1/acn3484.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142324/2/acn3484_am.pd

Handling our Failures

Speaker for Whitworth\u27s Forum program

What Does it Mean to be a World Christian

Speaker for Whitworth\u27s Forum program

Central American Trip

Speaker for Whitworth\u27s Forum program

Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity

Objectives Diabetes leads to cognitive impairment and is associated with age‐related neurodegenerative diseases including Alzheimer's disease ( AD ). Thus, understanding diabetes‐induced alterations in brain function is important for developing early interventions for neurodegeneration. Low‐capacity runner ( LCR ) rats are obese and manifest metabolic risk factors resembling human “impaired glucose tolerance” or metabolic syndrome. We examined hippocampal function in aged LCR rats compared to their high‐capacity 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 ‐inositol, taurine, and choline‐containing 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 proliferator‐activated receptor‐gamma coactivator 1 α , the NAD + ‐dependent 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 aged‐related dementing illnesses such as AD in humans. The metabolic and mitochondrial abnormalities observed in LCR rat hippocampus are similar to well‐described 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