Increased number of activated microglia in rat spinal cord during early stage of diabetic induction

Background: Diabetic neuropathy is a common chronic complication in diabetes mellitus. Such neuropathy associates with chronic inflammation and immune system activation. Microglia, a type of neuroglia, are involved in the immune system and are found in grey and white matter of the central nervous system, such as the brain and spinal cord. The spinal cord connects the peripheral nervous system and the higher brain centre. Hyperglycaemia during diabetes mellitus has been found to activate and increase number of microglia in the dorsal grey horn or column of the lumbar segments in spinal cord, which release several cytokines in the development of hypersensitivity in diabetic neuropathic pain.Materials and methods: Therefore, in this study, anatomical alterations of rat spinal microglia in all areas (dorsal, intermediate and ventral columns of grey matter and dorsal, lateral and ventral funiculi of white matter) in cervical enlargement, thoracic level and lumbosacral enlargement were observed in early stage of diabetic conditions by using light and transmission electron microscopies.Results: The numbers of microglia in all parts of grey and white matter of all spinal levels significantly increased in the diabetic group. The structures and ultrastructures of microglia in grey and white matter at cervical enlargement, thoracic level and lumbosacral enlargement similarly changed in diabetes. In diabetic rats, microglia became hypertrophied with a pale nucleus. Moreover, short fragments of rough endoplasmic reticulum, elevated numbers of lysosomes and numerous actin filaments in the cytoplasm were examined. Microglial phagocytosis of myelin and axonal debris were also observed. In this investigation, the morphology of spinal microglia during short-term diabetes became activated during hyperglycaemia. Conclusions: It is suggested that these changes may be involved in the development of diabetic neuropathic pain in the spinal cord

Mechanisms leading to increased vasodilator responses to calcitonin-gene-related peptide in mesenteric resistance arteries of early pregnant rats.

Contains fulltext : 69189.pdf (publisher's version ) (Closed access)The objective of this study was to explore the mechanism responsible for the higher relaxing responses of mesenteric arteries to calcitonin-gene-related peptide (CGRP) in pregnancy. We performed myograph and ligand binding studies to determine the role of matrix metalloproteinase-2 (MMP-2) and CGRP receptor density. MMP activity was manipulated in isolated arteries by exposing them to the blocking effects of doxycycline. Vascular activity of MMP-2 was studied by gelatin zymography, and CGRP receptor density was determined by ligand binding analysis. Compared to nonpregnant rats, CGRP elicited stronger arterial relaxation in pregnant rats. The latter effect was neither accompanied by a change in relaxing responses to direct activation of adenylyl cyclase by forskolin nor by a change in the response to stimulation of G-protein-coupled adrenergic receptors by isoproterenol. Doxycycline did not affect the stronger arterial relaxation in pregnancy in spite of the observed more than threefold higher arterial MMP-2 activity. Density of binding sites for [(125)I]CGRP in arteries from pregnant rats (64 +/- 14 fmol/mg protein) and from virgin rats (54 +/- 5 fmol/mg protein) were comparable. The results of this study provide evidence for increased coupling of CGRP receptors to adenylyl cyclase in early pregnancy