2018/03/18 by Daniel Rangel Rojas, Rohini Kuner, Rojas, Daniel Rangel +3
Medicine · #Acupuncture Treatment Research Studies #Botulinum Toxin and Related Neurological Disorders #Cell Behavior (q-bio.CB) #FOS: Biological sciences #Pain Mechanisms and Treatments #Tissues and Organs (q-bio.TO)
paper · pdf · doi:10.48550/arxiv.1803.06740
openalex publication_date 2018/03/18 · openalex created_date 2022/10/07 · openalex updated_date 2026/07/28
Diabetic-induced peripheral neuropathy (DPN) is a diabetic late complication.\nThe molecular mechanisms underlying the pathophysiology of nerve damage &\nsensory loss remain largely unclear. Recently, alterations in metabolic flux\nhave gained attention a basis for organ damage in diabetes; however, peripheral\nsensory neurons have not been adequately analyzed. In the present study, we\nattempted to delineate the role of alteration of metabolic pathways in relation\nto nerve damage & sensory loss. We employed STZ-injected mouse model of type1\ndiabetes. To investigate the progression of DPN by behavioral measurements of\nsensitivity to thermal & mechanical stimuli and quantitative assessment of\nintraepidermal nerve fiber density. We employed a MS-based screen to address\nalterations in levels of metabolites in peripheral sciatic nerve (SN) & amino\nacids (AA) in serum over several months post-STZ administration. Although\nhyperglycemia & body weight changes occurred early, sensory loss & reduced\nintraepithelial branching of nociceptive nerves was only evident at 22 wks\npost-STZ. The longitudinal metabolites screen in SN demonstrated that mice at\n12 and 22 wks post-STZ showed an early impairment the tricarboxylic acid. We\nfound that levels of citric acid, ketoglutaric acid, succinic acid, fumaric\nacid & malic acid were observed to be significantly reduced in SN at 22 wks\npost-STZ. In addition, we also found the increase in levels of sorbitol &\nL-Lactate in SN from 12 wks post-STZ injection. AA screen in serum showed that\nthe amino acids Val, Ile and Leu, increased more than 2-fold from 12 wks\npost-STZ. Similarly, the levels of Tyr, Asn, Ser, His, Ala, & Pro showed\nprogressive increase. Our results indicate that the impaired TCA cycle\nmetabolites in peripheral nerve is the primary cause of shunting metabolic\nsubstrate to compensatory pathways which leads to mitochondrial dysfunction &\nnerve damage.\n