Experimental Diabetes Attenuates Cerebral Cortical−Evoked Forelimb Motor Responses

Experimental Diabetes Attenuates Cerebral Cortical−Evoked Forelimb Motor Responses April J. Emerick 1 , Michael P. Richards 1 , Gwendolyn L. Kartje 2 3 , Edward J. Neafsey 3 and Evan B. Stubbs, Jr. 2 3 1 Research Services, Department of Veterans Affairs, Edward Hines, Jr. Hospital, Hines, Illinois 2 Department of Neurology, Stritch School of Medicine, Loyola University, Chicago, Illinois 3 Department of Cell Biology, Neurobiology, and Anatomy, Stritch School of Medicine, Loyola University, Chicago, Illinois Address correspondencereprint requests to Evan B. Stubbs, Jr., PhD, Neurology Service (127), Bldg. 1, Rm. F201, Edward Hines, Jr. VA Hospital, Hines, IL 60141. E-mail: evan.stubbs{at}med.va.gov Abstract Poorly controlled diabetes leads to debilitating peripheral complications, including retinopathy, nephropathy, and neuropathy. Chronic diabetes also impairs the central nervous system (CNS), leading to measurable deficits in cognition, somatosensory, and motor function. The cause of diabetes-associated CNS impairment is unknown. In this study, sustained hyperglycemia resulting from insulin deficiency was shown to contribute to CNS motor dysfunction. Experimental diabetes was induced in rats by streptozotocin (STZ) injection. CNS motor function was assessed by intracortical microstimulation of the sensorimotor cortex. Experimental diabetes significantly ( P < 0.01; n = 14) attenuated the number of motor cortical sites eliciting forelimb movements. The net area of the motor cortex representing the forelimb in diabetic rats was significantly reduced (4.0 ± 0.5 [control] vs. 2.4 ± 0.4 [STZ] mm 2 ; P < 0.05). Experimental diabetes attenuated the activation of some, but not all, forelimb motor cortical neurons. Insulin treatment of diabetic rats prevented the attenuation of cortical-evoked forelimb responses. Peripheral nerve−evoked responses were unaffected by this short period of diabetes, suggesting the absence of peripheral nerve dysfunction. This study showed that metabolic imbalance resulting from insulin deficiency elicits a marked attenuation of cortical-evoked motor function. Uncontrolled hyperglycemia, deficiencies of central insulin, or both may contribute to corticospinal motor dysfunction. CNS, central nervous system ICMS, intracortical microstimulation STZ, streptozotocin Footnotes The costs of publications of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accorda