ABSTRACT
The current epidemic of obesity and its associated metabolic syndromes impose unprecedented challenges to our society. Despite intensive research on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of the leptin neural pathway in the hypothalamus in the regulation of body weight homeostasis. Important hypothalamic neuropeptides have been identified as critical neurotransmitters from leptin-sensitive neurons to mediate leptin action. Recent research advance has significantly expanded the list of neurotransmitters involved in body weight-regulating neural pathways, including fast-acting neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. Given the limited knowledge on the leptin neural pathway for body weight homeostasis, understanding the function of neurotransmitters released from key neurons for energy balance regulation is essential for delineating leptin neural pathway and eventually for designing effective therapeutic drugs against the obesity epidemic.
Subject(s)
Animals , Humans , Energy Metabolism , Gene Expression , Hunger , Hypothalamus , Metabolism , Physiology , Leptin , Metabolism , Physiology , Neural Pathways , Metabolism , Neuropeptides , Genetics , Metabolism , Obesity , MetabolismABSTRACT
Objective To study the temporo-spatial changing laws of calcitonin gene-related peptide(CGRP)in the rat model of sciatic nerve ligation.Methods Totally 48 Sprague-Dawley rats were randomly divided into sham-operation group(n=6)and experimental groups which survived for 1,3,5,7,14,21,28 d respectively after sciatic nerve ligation(n=6 at each time point).The distribution and quantity of CGRP in sciatic nerve,dorsal root ganglion(DRG)and spinal cord were detected by immunohistochemistry and image analysis methods.Results A large amount of CGRP piled up in the sciatic nerve at 1 d after the ligation,significantly higher in proximal segment than that in distal segment,gradually dropping till disappear basically at 14 d in proximal segment and at 7 d in distal segment.The expression of CGRP in DRG at 7 d began to drop after the ligation,at 21 d to the minimal value and at 28 d lower than normal.The CGRP-immunoreactivety in ipsilateral spinal dorsal horn at 14 d decreased after operation,but the immuno-positive areas of CGRP were of no changes.There are no changes in the CGRP-positive spinal ventral motoneurons of all groups.Conclusion The changes of CGRP presented a temporo-spatial pattern following peripheral nerve legation,maybe resulting from the deficiency of neurothrophins from target organs.