O4‐03‐04: Type 3 Diabetes in Alzheimer's Disease: Ab‐Mediated Inhibition of EG5/Kinesin 5 Leads to Insulin Receptor and Glucose Transporter Mis‐Localization and Dysfunction

Wang, Athena; Lucero, Esteban; Bennett, Steven; Potter, Huntington

doi:10.1016/j.jalz.2016.06.621

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“…For example in fatal encephalopathy, a severe neurodevelopmental disorder, which is associated with hippocampal dysfunction, impaired mitochondrial function is present ( Haas et al, 2007 ), in addition to trafficking kinesin proteins deficiency ( Barel et al, 2017 ). Impaired kinesin and mitochondrial function have been reported in diabetes pathophysiology, as well ( Lu et al, 2004 ; Wang, Bennett, Potter, & Potter, 2016 ; Zilliox, Chadrasekaran, Kwan, & Russell, 2016 ). In this study, we used different behavioral tests to prove the cognitive impairments in diabetes and tried to evaluate the correlation of mitochondrial function, kinesin and dynein gene expression following diabetic encephalopathy.…”

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confidence: 99%

iabetic Encephalopathy Affecting Mitochondria and Axonal Transport Proteins

Gharaati

Nahavandi

Mojarad

et al. 2020

BCN

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Introduction: Diabetic encephalopathy is described as any cognitive and memory impairments associated with hippocampal degenerative changes, including the neurodegenerative process and decreased number of living cells. Mitochondrial diabetes (MD) appears following activation of mutant mitochondrial DNA and is a combination of diabetes and cognitive deficit. In this research, we showed the correlation of diabetic encephalopathy, dysfunctional mitochondria, and changes in the expression of axonal transport proteins (KIF5b, Dynein). Methods: Twenty-four male Wistar rats were divided into three groups: (n=8 in each group):1. Control + saline; 2. Diabetic, and 3. Diabetic + insulin. Before starting the experiments, the animals with blood sugar lower than 150 mg/dL entered the study. Diabetes induction was carried out by Intraperitoneal (IP) Streptozotocin (STZ) administration. Fasting Blood Sugar (FBS) and body weight was checked after the first week and at the end of the eighth week. Then, behavioral studies (elevated plus maze, Y-maze, and passive avoidance learning) were performed. After behavioral studies, blood samples were taken to measure serum insulin level and HgbA1c. Next, fresh hippocampal tissue was collected. Gene expression of motor proteins was assessed by real-time PCR and mitochondrial membrane potential by rhodamine123. Results: Our results showed the impairment of HgbA1c, serum insulin, FBS, and weight in the diabetic group (P<0.05). Behavioral tests revealed different degrees of impairment in diabetic rats (P<0.05). KIF5b mRNA expression increased in the hippocampus (P<0.05) with no change in dynein gene expression. These changes were associated with abnormal mitochondrial membrane potential (P<0.05). Conclusion: KIF5b mRNA up-regulation in hippocampal neurons of STZ-diabetic rats is a factor that can be involved in abnormal axonal transport and decreased MMP, leading to impairment of mitochondrial function. These manifestations showed mitochondrial dysfunction in diabetes and resulted in abnormal behavioral tests and diabetic encephalopathy.

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