Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses

Abstract

Vaughan CH, Bartness TJ. Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses. Am J Physiol Regul Integr Comp Physiol 302: R1049 -R1058, 2012. First published February 29, 2012 doi:10.1152/ajpregu.00640.2011.-Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96-and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (Tc) and IBAT (TIBAT) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. TIBAT and Tc were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.herpes simplex virus-1; capsaicin; sensory afferents; iButton; body temperature; interscapular brown adipose tissue temperature; calcitonin gene-related peptide RECENT REPORTS of functional brown adipose tissue (BAT) in humans has sparked more interest in mapping the connections between BAT and the brain in the hope of increasing thermogenesis thereby enhancing energy expenditure and reversing or preventing obesity (18,59,61). BAT is the major effector tissue in rodent thermogenesis (for review see Ref. 10) controlled nearly exclusively by the sympathetic nervous system (SNS) drive to the tissue (for review see Ref. 5). Because of reports of sensory nerve-associated neuropeptides at the level of the BAT pad (23,24,43), the potential for reciprocal connections between BAT and the brain would thus create the possibility of SNS-sensory feedback loops to control the thermogenic activity of the tissue in response to varying environmental and physiological cha...

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“…51 Moreover, using another viral transneuronal tract tracer, the H129 strain of herpes simplex virus 1, we labeled the central sensory circuits from WAT 52,53 and from BAT 53 to the brain. In terms of the latter, sensory innervation of BAT is necessary for the BAT temperature increase in response to acute cold exposure, as evidenced by decreases in BAT temperature when interscapular BAT was specifically sensory denervated via intra-interscapular BAT injection of the sensory nerve toxin, capsaicin.…”

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