leptin and Peripheral-Nervous-System-Diseases

To explore the efficacy and mechanism of hemoperfusion (HP) plus hemodialysis (HD) for peripheral neuropathy of uremic patients on maintenance hemodialysis.. A total of 66 uremic patients on hemodialysis during January 2014 and April 2011 were assigned randomly into HP+HD, low-flux HD and high-flux HD groups (n=22 each). The serum levels of leptin, endothelin-1 (ET-1), parathyroid hormone (PTH) and β-2 microglobulin were observed pre and post-treatment. And sensory conduction velocity (SCV) was detected simultaneously.. After 12-week treatment, the clinical symptoms of group HP+HD improved significantly with an effective rate of 90.91% while improvement was not obvious in groups high-flux and low-flux HD with effective rates of 31.82% and 13.64%. In HP+HD group, the levels of leptin, ET-1, PTH and β-2MG decreased, sensory conduction velocity increased (P<0.05) and clinical symptoms improved apparently. While in low-flux HD and high-flux HD groups, leptin, ET-1, PTH and β-2MG had no decrease and SCV showed no improvement (P>0.05). Correlation analysis showed that the levels of leptin, ET-1 and β-2MG were negatively correlated with SCV (r=-0.57, r=-0.47, r=-0.56). Yet PTH had no correlation with SCV (r=-0.23).. Hemoperfusion plus hemodialysis may improve the clinical symptoms of peripheral neuropathy of uremic patients on maintenance hemodialysis. And it is probably due to the fact that HP+HD effectively removes such plasma middle and macromolecular toxins as leptin, ET-1, PTH and β-2MG.

Topics: beta 2-Microglobulin; Endothelin-1; Hemoperfusion; Humans; Leptin; Parathyroid Hormone; Peripheral Nervous System Diseases; Renal Dialysis

Dyslipidemia has been identified as an important pathogenic risk factor for diabetic neuropathy, but current animal models do not adequately reproduce the lipid profile observed in human diabetics (increased triglycerides with an elevated LDL-cholesterol and reduced HDL-cholesterol). High fat feeding of mice produces hyperlipidemia, but mice are resistant to increases in the LDL to HDL ratio, reducing the potential for peripheral lipid deposits to impact neuropathy, as is postulated to occur in human subjects. Genetic manipulations provide an alternative approach to reproducing a neuropathic plasma lipid profile. Based on findings from the atherosclerosis literature, we began with knockout of ApoE. Since knockout of ApoE alone only partially mimics the human diabetic lipid profile, we examined the impact of its combination with a well-characterized model of type 2 diabetes exhibiting neuropathy, the db/db mouse. We added further gene manipulations to increase hyperlipidemia by using mice with both ApoE and ApoB48 knockout on the ob/+ (leptin mutation) mice. In all of these models, we found that either the db/db or ob/ob genotypes had increased body weight, hyperlipidemia, hyperglycemia, and evidence of neuropathy compared with the control groups (db/+ or ob/+, respectively). We found that ApoE knockout combined with leptin receptor knockout produced a lipid profile most closely modeling human dyslipidemia that promotes neuropathy. ApoE knockout combined with additional ApoB48 and leptin knockout produced similar changes of smaller magnitude, but, notably, an increase in HDL-cholesterol. Our data suggest that the overall effects of ApoE knockout, either directly upon nerve structure and function or indirectly on lipid metabolism, are insufficient to significantly alter the course of diabetic neuropathy. Although these models ultimately do not deliver optimal lipid profiles for translational diabetic neuropathy research, they do present glycemic and lipid profile properties of value for future therapeutic investigations.

Topics: Animals; Apolipoproteins E; Behavior, Animal; Blood Glucose; Body Weight; Cholesterol; Data Interpretation, Statistical; Disease Models, Animal; Dyslipidemias; Electrophysiological Phenomena; Leptin; Lipids; Lipoproteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pain Measurement; Peripheral Nervous System Diseases; Triglycerides

Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1beta through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain.

Topics: Animals; Interleukin-1beta; Janus Kinase 2; Leptin; Male; Mice; Mice, Inbred C57BL; Pain; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Receptors, Leptin; Receptors, N-Methyl-D-Aspartate; Spinal Cord; STAT3 Transcription Factor