Abstract
Male Wistar rats, initially maintained at an ambient temperature (T a) of 24°C, were subjected to a constant high T a of 32°C (HE) or were constantly kept at 24°C (controls, CN). Bromodeoxyuridine (BrdU) was intraperitoneally injected daily for five consecutive days after commencing heat exposure. On the 6th, 13th, 23rd, 33rd, 43rd, and 53rd day of heat exposure, rats’ brains were removed. Immunohistochemical analysis showed that the numbers of BrdU-positive cells in the hypothalamus of HE were significantly and consistently greater than those of CN. In HE, the number of BrdU-positive cells double-stained by a mature neuron marker increased abruptly after 33 days of heat exposure by about seven times. This was not the case in CN. The results suggest that heat exposure facilitates proliferation of neuronal progenitor cells in the hypothalamus and promotes differentiation to neurons, which might have certain relation to establishing long-term heat acclimation in rats.
Similar content being viewed by others
References
Almeida MC, Steiner AA, Branco LG, Romanovsky AA (2006) Neural substrate of cold-seeking behavior in endotoxin shock. PLoS ONE 1:e1
Armstrong LE, Stoppani J (2002) Central nervous system control of heat acclimation adaptations: an emerging paradigm. Rev Neurosci 13:271–285
Baldassarre G, Boccia A, Bruni P, Sandomenico C, Barone MV, Pepe S, Angrisano T, Belletti B, Motti ML, Fusco A, Viglietto G (2000) Retinoic acid induces neuronal differentiation of embryonal carcinoma cells by reducing proteasome-dependent proteolysis of the cyclin-dependent inhibitor p27. Cell Growth Differ 11:517–526
Bratincsák A, Palkovits M (2004) Activation of brain areas in rat following warm and cold ambient exposure. Neuroscience 127:385–397
Brown JP, Couillard-Després S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10
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
Cunningham JJ, Roussel M (2001) Cyclin-dependent kinase inhibitors in the development of the central nervous system. Cell Growth Differ 12:387–396
Demicka A, Caputa M (1993) Effect of warm rearing on the development of thermolytic effectors in rats. J Therm Biol 18:257–262
Dimicco JA, Zaretsky DV (2007) The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol 292:R47–R63
Dyer MA, Cepko CL (2001) p27kip1 and p57kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci 21:4259–4271
Eynan M, Knubuvetz T, Meiri U, Navon G, Gerstenblith G, Bromberg Z, Hasin Y, Horowitz M (2002) Heat acclimation-induced elevated glycogen, glycolysis, and low thyroxine improve heart ischemic tolerance. J Appl Physiol 93:2095–2104
Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438
Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS (1992) Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci 12:3642–3650
Guillery RW, Herrup K (1997) Quantification without pontification: choosing a method for counting objects in sectioned tissues. J Comp Neurol 386:2–7
Horowitz M, Meiri U (1985) Thermoregulatory activity in the rat: effects of hypohydration, hypovolemia and hypertonicity and their interaction with short term heat acclimation. Comp Biochem Physiol 82:577–582
Horowitz M, Sugimoto E, Okuno T, Morimoto T (1998) Changes in blood volume and vascular compliance during body heating in rats. Pflugers Arch 412:354–358
Horowitz M, Kaspler P, Simon E, Gerstberger R (1999) Heat acclimation and hypohydration: involvement of central angiotensin II receptors in thermoregulation. Am J Physiol 277:47–55
Horowitz M (2002) From molecular and cellular to integrative heat defense during exposure to chronic heat. Comp Biochem Physiol A Mol Integr Physiol 131:475–483
Joëls M, Karst H, Alfarez D, Heine VM, Qin Y, van Riel E, Verkuyl M, Lucassen PJ, Krugers HJ (2004) Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 7:221–231
Kanosue K, Yanase-Fujiwara M, Hosono T (1994) Hypothalamic network for thermoregulatory vasomotor control. Am J Physiol Regul Integr Comp Physiol 267:R283–R288
Kawakita E, Hashimoto M, Shido O (2006) Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 139:991–997
Kokoeva MV, Yin H, Flier JS (2005) Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 310:679–683
Labunskay G, Meiri N (2006) R-Ras3/(M-Ras) is involved in thermal adaptation in the critical period of thermal control establishment. J Neurobiol 66:56–70
Li GH, Katakura M, Maruyama M, Enhkjargal B, Matsuzaki K, Hashimoto M, Shido O (2008) Changes of noradrenaline-induced contractility and gene expression in aorta of rats acclimated to heat in two different modes. Eur J Appl Physiol 104:29–40
Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179–193
Lu J, Zhang YH, Chou TC, Gaus SE, Elmquist JK, Shiromani P, Saper CB (2001) Contrasting effects of ibotenate lesions of the paraventricular nucleus and subparaventricular zone on sleep-wake cycle and temperature regulation. J Neurosci 21:4864–4874
Lukaszewicz A, Savatier P, Cortay V, Kennedy H, Dehay C (2002) Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells. J Neurosci 22:6610–6622
Magavi SS, Leavitt BR, Macklis JD (2000) Induction of neurogenesis in the neocortex of adult mice. Nature 405:951–955
Markakis EA, Gage FH (1999) Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. J Comp Neurol 406:449–460
Markakis EA, Palmer TD, Randolph-Moore L, Rakic P, Gage FH (2004) Novel neuronal phenotypes from neural progenitor cells. J Neurosci 24:2886–2897
Maruyama M, Hara T, Hashimoto M, Koga M, Shido O (2006) Alterations of calf venous and arterial compliance following acclimation to heat administered at a fixed daily time in humans. Int J Biometeorol 50:269–274
McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–122
Nagashima K, Nakai S, Tanaka M, Kanosue K (2000) Neuronal circuitries involved in thermoregulation. Auton Neurosci 85:18–25
Nakamura K, Morrison SF (2008) A thermosensory pathway that controls body temperature. Nat Neurosci 11:62–71
Nakayama T (1985) Thermosensitive neurons in the brain. Jpn J Physiol 35:375–389
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edition. Academic, New York
Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (2001) Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 21:6706–6717
Romanovsky AA (2007) Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol 292:R37–R46
Saha SK, Ohno T, Tsuchiya K, Kuroshima A (2000) Adaptive modification of membrane phospholipid fatty acid composition and metabolic thermosuppression of brown adipose tissue in heat-acclimated rats. Int J Biometeorol 43:163–168
Sakurada S, Shido O, Sugimoto N, Fujikake K, Nagasaka T (1994) Changes in hypothalamic temperature of rats after daily exposure to heat at a fixed time. Pflügers Arch 429:291–293
Schwimmer H, Eli-Berchoer L, Horowitz M (2006) Acclimatory-phase specificity of gene expression during the course of heat acclimation and superimposed hypohydration in the rat hypothalamus. J Appl Physiol 100:1992–2003
Shein NA, Doron H, Horowitz M, Trembovler V, Alexandrovich AG, Shohami E (2007) Altered cytokine expression and sustained hypothermia following traumatic brain injury in heat acclimated mice. Brain Res 1185:313–320
Sugimoto N, Sakurada S, Shido O (1999) Selected ambient temperatures of rats acclimated to heat given on various schedules. Pflügers Arch 438:766–770
Thomaidou D, Mione MC, Cavanagh JF, Parnavelas JG (1997) Apoptosis and its relation to the cell cycle in the developing cerebral cortex. J Neurosci 17:1075–1085
Thornhill JA, Halvorson I (1994) Electrical stimulation of the posterior and ventromedial hypothalamic nuclei causes specific activation of shivering and nonshivering thermogenesis. Can J Physiol Pharmacol 72:89–96
Vogel P, Dux E, Wiessner C (1997) Evidence of apoptosis in primary neuronal cultures after heat shock. Brain Res 764:205–213
Watanabe T, Fujioka T, Hashimoto M, Nakamura S (1998) Stress and brain angiotensin II receptors. Crit Rev Neurobiol 12:305–317
Wyndham CH (1967) Effect of acclimatization on the sweat rate-rectal temperature relationship. J Appl Physiol 22:27–30
Xu Y, Tamamaki N, Noda T, Kimura K, Itokazu Y, Matsumoto N, Dezawa M, Ide C (2005) Neurogenesis in the ependymal layer of the adult rat 3rd ventricle. Exp Neurol 192:251–264
Yoshida K, Konishi M, Nagashima K, Saper CB, Kanosue K (2005) Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter. Neuroscience 133:1039–1046
Acknowledgments
This study was partly supported by The Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant-in-Aid for Young Scientists (B) 20790192. The authors also wish to thank John Telloyan for his English assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Matsuzaki, K., Katakura, M., Hara, T. et al. Proliferation of neuronal progenitor cells and neuronal differentiation in the hypothalamus are enhanced in heat-acclimated rats. Pflugers Arch - Eur J Physiol 458, 661–673 (2009). https://doi.org/10.1007/s00424-009-0654-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-009-0654-2