A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity

Hong Zheng, Xuefei Liu, Yulong Li, Kaushik P Patel

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Accumulated evidence indicates that obesity-induced type 2 diabetes (T2D) is associated with enhanced sympathetic activation. The present study was conducted to investigate the role for leptin-glutamate signaling within the hypothalamus in regulating sympathetic nerve activity. In anesthetized rats, microinjections of leptin (5 ng 100 ng) into the arcuate nucleus (ARCN) and paraventricular nucleus (PVN) induced increases in renal sympathetic nerve activity (RSNA), blood pressure (BP), and heart rate (HR). Prior microinjections of NMDA receptor antagonist AP5 (16 pmol) into the ARCN or PVN reduced leptin-induced increases in RSNA, BP, and HR in both ARCN and PVN. Knockdown of a leptin receptor with siRNA inhibited NMDA-induced increases in RSNA, BP, and HR in the ARCN but not in the PVN. Confocal calcium imaging in the neuronal NG108 and astrocytic C6 cells demonstrated that preincubation with leptin induced an increase in intracellular calcium green fluorescence when the cells were challenged with glutamate. In high-fat diet and low-dose streptozotocin-induced T2D rats, we found that leptin receptor and NMDA NR1 receptor expressions in the ARCN and PVN were significantly increased. In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D.

Original languageEnglish (US)
Article number2361675
JournalNeural Plasticity
Volume2017
DOIs
StatePublished - Jan 1 2017

Fingerprint

Arcuate Nucleus of Hypothalamus
Paraventricular Hypothalamic Nucleus
Leptin
Glutamic Acid
Type 2 Diabetes Mellitus
Leptin Receptors
Heart Rate
Microinjections
Blood Pressure
Kidney
Obesity
High Fat Diet
N-Methylaspartate
Streptozocin
N-Methyl-D-Aspartate Receptors
Small Interfering RNA
Hypothalamus
Fluorescence
Calcium

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity. / Zheng, Hong; Liu, Xuefei; Li, Yulong; Patel, Kaushik P.

In: Neural Plasticity, Vol. 2017, 2361675, 01.01.2017.

Research output: Contribution to journalArticle

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