Regulation of the Intracerebroventricular Administration of Brain-Derived Neurotrophic Factor on Baroreflex Function and Insulin Sensitivity in Rats

Ming-Fu Wang ； Yin-Ching Chan ； Hsu-Tung Lee ； Ling-Zong Hong

《The Chinese Journal of Physiology》 55卷3期 (2012/06) Pp. 184-191

https://doi.org/10.4077/CJP.2012.BAA015

並列摘要

In addition to its well-established neurotrophic effects, brain-derived neurotrophic factor (BDNF) has also been shown to regulate glucose metabolism. The present study was conducted to determine whether BDNF has effects on baroreflex sensitivity (BRS) and whole-body insulin sensitivity through modulation of autonomic nervous function in normal rats. Male Sprague-Dawley rats were treated with intracerebroventricular BDNF (20 μg per rat, 10 μl; BDNF) or artificial cerebrospinal fluid (10 μl; control) at an infusion rate of 1 μl/min in conscious state. The whole-body insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp technique. BRS in response to phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS) was assessed using linear regression analysis. The sympathetic and parasympathetic influences on BRS were investigated by pharmacological autonomic blockade. When compared to the control rats, blood glucose levels were slightly but significantly decreased in BDNF-treated rats. However, plasma insulin levels were reduced by about 30%. The whole-body insulin sensitivity was increased in BDNF-treated rats. In addition, blood pressure was increased but heart rate remained unchanged after BDNF treatment. Enhanced PE-BRS was also observed in the BDNF-treated rats, which was attributed to the abnormal parasympathetic activation as revealed by the results of the pharmacological blockade study with methylatropine. Results of the present demonstrate that central BDNF plays an important role in the regulation of whole-body insulin sensitivity and baroreflex function. The data indicate that the alteration of autonomic nervous function may play a role in the effects of BDNF.

並列關鍵字

baroreflex ； cardiac autonomic ； insulin sensitivity ； intracerebroventricular ； neurotrophin

參考文獻

Balkowiec, A.,Kunze, D. L.,Katz, D. M.(2000).Brain-derived neurotrophic factor acutely inhibits AMPA-mediated currents in developing sensory relay neurons.J. Neurosci..20,1904-1911.

Bariohay, B.,Tardivel, C.,Pio, J.,Jean, A.,Felix, B.(2008).BDNFTrkB signaling interacts with the GABAergic system to inhibit rhythmic swallowing in the rat.Am. J. Physiol. Regul. Integr. Comp. Physiol..295,R1050-R1059.

Brady, R.,Zaidi, S. I.,Mayer, C.,Katz, D.M.(1999).BDNF is a targetderived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons.J. Neurosci..19,2131-2142.

Chen, Q. H.,Toney, G. M.(2010).In vivo discharge properties of hypothalamic paraventricular nucleus neurons with axonal projections to the rostral ventrolateral medulla.J. Neurophysiol..103,4-15.

Cho, H. J.,Yoon, K. T.,Kim, H. S.,Lee, S. J.,Kim, J. K.,Kim, D. S.,Lee, W. J.(1999).Expression of brain-derived neurotrophic factor in catecholaminergic neurons of the rat lower brainstem after colchicine treatment or hemorrhage.Neuroscience.92,901-909.