Abstract
The hypothalamus is critical for regulating thermogenesis, but the role of monoamines in specific hypothalamic subregions in thermogenesis is not thoroughly established. The purpose of this study was to confirm changes of body temperature (T b) and thermoregulatory parameters upon inhibition of neural activity in hypothalamic subregions in freely moving rats. In addition, the pattern of monoamine release in these nuclei was measured during active thermoregulation using microdialysis. Tetrodotoxin (TTX) was perfused into the ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), or posterior hypothalamus (PH) at two different ambient temperatures (5 or 23 °C). Using telemetry, we continuously measured the T b and the heart rate (HR) as an index of heat production as well as locomotor activity (Act). Tail skin temperature (T tail) was also continuously measured as an index of heat loss. Although the perfusion of TTX into hypothalamic subregions had no effect on any of the measured thermoregulatory parameters at an ambient temperature of 23 °C, it induced significant T b decrease under cold conditions only when perfused into the DMH and the PH. In contrast, the HR decreased only after perfusion of TTX into the PH during cold conditions, while the T tail and Act remained unchanged. Serotonin (5-HT) in the DMH and dopamine (DA) metabolite 3,4-Dihydroxyphenylacetic acid in the PH, but not noradrenaline, increased significantly during exposure to cold temperatures. Our results indicate that the DMH and the PH, but not the VMH, are particularly involved in heat production under cold conditions. In addition, 5-HT in the DMH and DA in the PH may be involved in thermogenesis.
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Abbreviations
- 5-HT:
-
Serotonin
- 5-HIAA:
-
5-Hydroxyindoleacetic acid
- Ad:
-
Adrenaline
- Act:
-
Locomotor activity
- DA:
-
Dopamine
- DMH:
-
Dorsomedial hypothalamus
- DOPAC:
-
3,4-Dihydroxyphenylacetic acid
- HPLC:
-
High-performance liquid chromatography
- HR:
-
Heart rate
- HVA:
-
Homovanillic acid
- IBAT:
-
Interscapular brown adipose tissue
- NA:
-
Noradrenaline
- PH:
-
Posterior hypothalamus
- PO/AH:
-
Preoptic area and anterior hypothalamus
- PRV:
-
Pseudorabies virus
- T b :
-
Body temperature
- T tail :
-
Tail skin temperature
- TTX:
-
Tetrodotoxin
- VMH:
-
Ventromedial hypothalamus
References
Amir S (1990a) Intra-ventromedial hypothalamic injection of glutamate stimulates brown adipose tissue thermogenesis in the rat. Brain Res 511:341–344
Amir S (1990b) Activation of brown adipose tissue thermogenesis by chemical stimulation of the posterior hypothalamus. Brain Res 534:303–308
Bamshad M, Song CK, Bartness TJ (1999) CNS origins of the sympathetic nervous system outflow to brown adipose tissue. Am J Physiol 276:R1569–R1578
Boulant JA, Dean JB (1986) Temperature receptors in the central nervous system. Annu Rev Physiol 48:639–654
Cano G, Passerin AM, Schiltz JC, Card JP, Morrison SF, Sved AF (2003) Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure. J Comp Neurol 460:303–326
Carlisle HJ, Laudenslager ML (1979) Observation on thermoregulatory effects of preoptic warming in rats. Physiol Behav 23:723–732
Cerri M, Del Vecchio F, Mastrotto M, Luppi M, Martelli D, Perez E, Tupone D, Zamboni G, Amici R (2014) Enhanced slow-wave EEG activity and thermoregulatory impairment following the inhibition of the lateral hypothalamus in the rat. PLoS One 9(11):e112849
Chambers JB, Williams TD, Nakamura A, Henderson RP, Overton JM, Rashotte ME (2000) Cardiovascular and metabolic responses of hypertensive and normotensive rats to one week of cold exposure. Am J Physiol 279:R1486–R1494
Chen XM, Hosono T, Yoda T, Fukuda Y, Kanosue K (1998) Efferent projection from the preoptic area for the control of non-shivering thermogenesis in rats. J Physiol 512:883–892
Dean JB, Boulant JA (1989) In vitro localization of thermosensitive neurons in the rat diencephalon. Am J Physiol 257:R57–R64
Dimicco JA, Zaretsky DV (2007) The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol 292:R47–R63
Freeman PH, Wellman PJ (1987) Brown adipose tissue thermogenesis induced low level electrical stimulation of hypothalamus in rats. Brain Res Bull 18:7–11
Fukuhara K, Kvetnansky R, Cizza G, Pacak K, Ohara H, Goldstein DS, Kopin IJ (1996) Interrelations between sympathoadrenal system and hypothalamo-pituitary-adrenocortical/thyroid systems in rats exposed to cold stress. J Neuroendocrinol 8:533–541
Gilbert TM, Blatteis CM (1977) Hypothalamic thermoregulatory pathways in the rat. J Appl Physiol 43:770–777
Gordon CJ (1990) Thermal biology of the laboratory rat. Physiol Behav 47:963–991
Halvorson I, Thornhill JA (1993) Posterior hypothalamic stimulation of anesthetized normothermic and hypothermic rats evokes shivering thermogenesis. Brain Res 610:208–215
Halvorson I, Gregor L, Thornhill JA (1990) Brown adipose tissue thermogenesis is activated by electrical and chemical (l-glutamate) stimulation of the ventromedial hypothalamic nucleus in cold-acclimated rats. Brain Res 522:76–82
Hasegawa H, Yazawa T, Yasumatsu M, Otokawa M, Aihara Y (2000) Alternation in dopamine metabolism in the thermoregulatory center of exercising rats. Neurosci Lett 289:161–164
Hasegawa H, Ishiwata T, Saito T, Yazawa T, Aihara Y, Meeusen R (2005) Inhibition of the preoptic area and anterior hypothalamus by tetrodotoxin alters thermoregulatory functions in exercising rats. J Appl Physiol 98:1458–1462
Hasegawa H, Takatsu S, Ishiwata T, Tanaka H, Sarre S, Meeusen R (2011) Continuous monitoring of hypothalamic neurotransmitters and thermoregulatory responses in exercising rats. J Neurosci Methods 202:119–123
Holt SJ, Wheal HV, York DA (1987) Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres. Brain Res 405:227–233
Ishiwata T, Hasegawa H, Yazawa T, Otokawa M, Aihara Y (2002) Functional role of the preoptic area and anterior hypothalamus in thermoregulation in freely moving rats. Neurosci Lett 325:167–170
Ishiwata T, Saito T, Hasegawa H, Yazawa T, Otokawa M, Aihara Y (2004) Changes of body temperature and extracellular serotonin level in the preoptic area and anterior hypothalamus after thermal or serotonergic pharmacological stimulation of freely moving rats. Life Sci 75:2665–2675
Ishiwata T, Saito T, Hasegawa H, Yazawa T, Kotani Y, Otokawa M, Aihara Y (2005) Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures. Brain Res 1048:32–40
Ishiwata T, Oshimoto A, Saito T, Kotani Y, Nomoto S, Aihara Y, Hasegawa H, Greenwood BN (2016) Possible mechanisms of hypothermia after inhibition of the median or dorsal raphe nucleus of freely moving rats. NeuroReport 27:1287–1292
Jones DL, Veale WL, Cooper KE (1980) Alterations in body temperature elicited by intrahypothalamic administration of tetrodotoxin, ouabain and A23187 ionophore in the conscious cat. Brain Res Bull 5:75–80
Kerman IA, Akil H, Watson SJ (2006) Rostral elements of sympatho-motor circuitry: a virally mediated transsynaptic tracing study. J Neurosci 26:3423–3433
Kiyohara T, Miyata S, Nakamura T, Shido O, Nakashima T, Shibata M (1995) Differences in Fos expression in the rat brains between cold and warm ambient exposures. Brain Res Bull 38:193–201
Kobayashi A, Osaka T, Namba Y, Inoue S, Kimura S (1999) CGRP microinjection into the ventromedial or dorsomedial hypothalamic nucleus activates heat production. Brain Res 827:176–184
Li Q, Thornhill J (1990) Thermoresponsiveness of posterior hypothalamic (PH) neurons of rats to scrotal and abdominal thermal stimulation. Brain Res 794:80–87
Martelli D, Luppi M, Cerri M, Tupone D, Mastrotto M, Perez E, Zamboni G, Amici R (2014) The direct cooling of the preoptic-hypothalamic area elicits the release of thyroid stimulating hormone during wakefulness but not during REM sleep. PLoS One 9:e87793
McKitrick DJ (2000) Expression of Fos in the hypothalamus of rats exposed to warm and cold temperatures. Brain Res Bull 53:307–315
Monda M, Viggiano A, De Luca V (2000) Intracerebroventricular injection of prostaglandin E(1) changes concentrations of biogenic amines in the posterior hypothalamus of the rat. Brain Res 873:197–202
Morimoto A, Murakami N, Ono T, Watanabe T, Sakata Y (1986) Stimulation of ventromedial hypothalamus induces cold defense responses in conscious rabbits. Am J Physiol 250:R560–R566
Morishima MS, Gale CC (1972) Relationship of blood pressure and heart rate to temperature in baboons. Am J Physiol 223:387–395
Morrison SF (2016) Central control of body temperature. F1000Res 5:880. doi:10.12688/f1000research.7958.1
Morrison SF, Madden CJ (2014) Central nervous system regulation of brown adipose tissue. Comp Physiol 4:1677–1713
Nakamura K, Morrison SF (2011) Central efferent pathways for cold-defensive and febrile shivering. J Physiol 589:3641–3658
Ootsuka Y, Tanaka M (2015) Control of cutaneous blood flow by central nervous system. Temperature (Austin) 2:392–405
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, New York
Perkins MN, Rothwell NJ, Stock MJ, Stone TW (1981) Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature 289:401–402
Quan N, Blatteis CM (1989) Microdialysis: a system for localized drug delivery into the brain. Brain Res Bull 22:621–625
Rathner JA, Madden CJ, Morrison SF (2008) Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction. Am J Physiol 295:R343–R354
Redfors B, Shao Y, Omerovic E (2014) Influence of anesthetic agent, depth of anesthesia and body temperature on cardiovascular functional parameters in the rat. Lab Anim 41:6–14
Romanovsky AA (2007) Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol 292:R37–R46
Saito T (2011) Effect of several durations of cold exposure on brain monoamines concentrations in the dorso medial hypothalamus in rats. J Kyoei Univ 9:55–59
Saito T, Ishiwata T, Hasegawa H, Nomoto S, Otokawa M, Aihara Y (2005) Changes in monoamines in rat hypothalamus during cold acclimation. J Thermal Biol 30:229–235
Saito T, Ishiwata T, Hasegawa H, Nomoto S, Kotani Y, Otokawa M, Aihara Y (2008) Effect of chronic cold exposure on noradrenergic modulation in the preoptic area of thermoregulation in freely moving rats. Life Sci 83:79–84
Song K, Wang H, Kamm GB, Pohle J, Reis FC, Heppenstall P, Wende H, Siemens J (2016) The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia. Science 353:1393–1398
Tan CL, Cooke EK, Leib DE, Lin YC, Daly GE, Zimmerman CA, Knight ZA (2016) Warm-sensitive neurons that control body temperature. Cell 167:47–59
Tanaka M, Tonouchi M, Hosono T, Nagashima K, Yanase-Fujiwara M, Kanosue K (2001) Hypothalamic region facilitating shivering in rats. Jpn J Physiol 51:625–629
Tanaka M, McKinley MJ, McAllen RM (2011) Preoptic-raphé connections for thermoregulatory vasomotor control. J Neurosci 31:5078–5088
Van Daele DJ, Cassell MD (2009) Multiple forebrain systems converge on motor neurons innervating the thyroarytenoid muscle. Neuroscience 162:501–524
Westerink BHC (1995) Brain microdialysis and its application for the study of animal behaviour. Behav Brain Res 70:103–124
Wixson SK, White WJ, Hughes HC Jr, Lang CM, Marshall WK (1987) The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on core and surface body temperature regulation in adult male rats. Lab Anim Sci 37:743–749
Yasumatsu M, Yazawa T, Otokawa M, Kuwasawa K, Hasegawa H, Aihara Y (1998) Monoamines, amino acids and acetylcholine in the preoptic area and anterior hypothalamus of rats: measurements of tissue extracts and in vivo microdialysates. Comp Biochem Physiol A 121:13–23
Zaretskaia MV, Zaretsky DV, Shekhar A, DiMicco JA (2002) Chemical stimulation of the dorsomedial hypothalamus evokes non-shivering thermogenesis in anesthetized rats. Brain Res 928:113–125
Zhang YH, Yanase-Fujiwara M, Hosono T, Kanosue K (1995) Warm and cold signals from the preoptic area: which contribute more to the control of shivering in rats? J Physiol 485:195–202
Zhao ZD, Yang WZ, Gao C, Fu X, Zhang W, Zhou Q, Chen W, Ni X, Lin JK, Yang J, Xu XH, Shen WL (2017) A hypothalamic circuit that controls body temperature. Proc Natl Acad Sci USA 114:2042–2047
Acknowledgements
The present study was partly supported by JSPS KAKENHI Grant Number JP23700684 (T.I.). We thank Drs. Yasutsugu Aihara (Tokyo Metropolitan University), Hiroshi Hasegawa (Hiroshima University), and Takehito Saito (Kyoei University) for valuable discussion throughout the study.
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Communicated by G. Heldmaier.
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Ishiwata, T., Greenwood, B.N. Changes in thermoregulation and monoamine release in freely moving rats during cold exposure and inhibition of the ventromedial, dorsomedial, or posterior hypothalamus. J Comp Physiol B 188, 541–551 (2018). https://doi.org/10.1007/s00360-017-1130-5
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DOI: https://doi.org/10.1007/s00360-017-1130-5