Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats

Abstract

Osaka, Toshimasa. Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats. Am J Physiol Regul Integr Comp Physiol 287: R306 -R313, 2004. First published March 18, 2004 10.1152/ajpregu.00003.2004.-Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA A receptor agonist muscimol (100 M, 100 nl) into the preoptic area (POA) of the hypothalamus increased the rate of whole body O 2 consumption (V O2) and the body core (colonic) temperature of urethane-chloralose-anesthetized, artificially ventilated rats. The most sensitive site was the dorsomedial POA at the level of the anterior commissure. The GABA-induced thermogenesis was accompanied by a tachycardic response and electromyographic (EMG) activity recorded from the femoral or neck muscles. Pretreatment with muscle relaxants (1 mg/kg pancuronium bromide ϩ 4 mg/kg vecuronium bromide iv) prevented GABAinduced EMG activity but had no significant effect on GABA-induced thermogenesis. However, pretreatment with the ␤-adrenoceptor propranolol (5 mg/kg iv) greatly attenuated the GABA-induced increase in V O2 and tachycardic responses. Accordingly, the GABA-induced increase in V O2 reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28°C water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA A receptor antagonist bicuculline (500 M, 100 nl), but not the vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that GABA and GABA A receptors in the POA mediate cold information arising from the skin for eliciting coldinduced thermogenesis. thermoafferent; neurotransmitter; nonshivering thermogenesis THE PREOPTIC AREA (POA) of the hypothalamus is considered to be the primary locus for body temperature regulation, because it integrates thermoafferent signals from the skin and other parts of the body and exerts control over the thermoefferent mechanisms (3,8,15,25). However, the neurotransmitter that mediates thermoafferent signals to the POA is largely unknown, even though there is a great deal of electrophysiological and pharmacological evidence implicating a role for a variety of neurotransmitters, peptides, and cytokines (2, 6, 10, 32).The POA contains GABAergic neurons (27), spontaneously releases GABA to the extracellular space (9, 29), and expresses GABA A receptors (7). Perfusion of the POA with the GABA A agonist muscimol induces hyperthermia, which is not affected by antipyretics and is thus independent of fever, in freely behaving rats (19). Warm-sensitive and thermally insensitive neurons are inhibited by the GABAergic mechanism in the POA (28). Furthermore, it was recently reported that the extracellular GABA level in the POA was increased by acute cold exposure and decreased by heat exposure (14). Therefore, it is possible that GABA is involved in the mechanism of thermoregulation in the POA.Body temperature is regulated by the balance between heat ...

Preoptic–Raphé Connections for Thermoregulatory Vasomotor Control

“…6 B, 7). Heart rate and expired CO 2 both fell slightly, as described previously (Osaka, 2004). Vehicle injected into the same position in the CLPO in six of seven rats had no effect on any of these variables (Fig.…”

“…The currently accepted model of thermoregulation is that both heat production and heat loss are under tonic inhibitory control by warm-sensitive preoptic neurons (Zhang et al, 1995;Chen et al, 1998;Nagashima et al, 2000;Osaka, 2004;Rathner et al, 2008;Tanaka et al, 2009), with those regulating heat production projecting to the DMH and those regulating heat dissipation projecting directly to the medullary raphé (Nakamura and Morrison, 2007;Morrison et al, 2008;Rathner et al, 2008). No significant output from the preoptic region has been attributed to coldsensitive cells.…”

“…This is relevant because an inhibitory action from this region on BAT SNA and thermogenesis has been identified (Osaka, 2004;Nakamura and Morrison, 2007). To check for any inhibitory action on tail SNA, the tests were repeated in six additional rats (cold baseline series).…”

A thermosensory pathway mediating heat-defense responses

“…Nanoinjection mapping in POA subregions with inhibitory agents to evoke cold-defense responses has suggested that such inhibitory, descending projection neurons are distributed mostly in the medial POA (28,29), although some of these neurons controlling CVCs also might be distributed in the MnPO (29). Our previous results support a local POA mechanism for eliciting cold-defense responses in which cutaneous cool signaling from the LPBel activates GABAergic interneurons in the MnPO, which then inhibit the tonic activity of the inhibitory projection neurons in the medial POA that innervate neurons in the caudal brain regions, including the dorsomedial hypothalamus and rostral medullary raphe, whose activation leads to sympathetic cold-defense responses (8,27) (Fig.…”

Effects of Dăoyĭn Qìgōng in postpolio syndrome patients with cold intolerance

“…Exercises that combine movement with breathing, such as yoga, cause significant increases in brain levels of gamma-aminobutyric acid (GABA) post-workout 46 . One study demonstrated that the action of GABA in the mid-dorsal region of the POA causes an increase in the core temperature through stimulation of thermogenesis in brown adipose tissue 47 . Finally, the literature suggests that CNS plasticity may be induced by functional or motor tasks 48,49 .…”