Elsevier

Brain Research Bulletin

Volume 53, Issue 3, October 2000, Pages 307-315
Brain Research Bulletin

Expression of Fos in the hypothalamus of rats exposed to warm and cold temperatures

https://doi.org/10.1016/S0361-9230(00)00346-4Get rights and content

Abstract

Fos-like immunoreactivity was investigated in hypothalamic areas involved in central thermoregulatory processes. Different groups of urethane anaesthetized rats (n = 36) were exposed to: (1) 23.5°C for 1 h (control); (2) 5°C for 20 min (short cold); (3) 5°C for 1 h (long cold); (4) 47°C for 10 min (short warm) and (5) 47°C for 1 h (long warm). Fos was present in the supramammillary nucleus, supraoptic nucleus and paraventricular hypothalamus of all (control and long and short, warm- and cold-exposed) rats. Fos was seen in the dorsomedial, medial and ventromedial hypothalamus of rats with long or short exposure to both warm and cold temperatures, and in the medial preoptic area and lateral anterior hypothalamus of long and short warm-exposed, and long cold-exposed, rats. Fos was present in the hypothalamus of long and short cold-exposed animals only in the posterior hypothalamus, and in the anterior hypothalamus (central and anterior divisions), suprachiasmatic nucleus and ventrolateral preoptic area of short and long warm-exposed rats. These results provide information on the location of neurons in rat hypothalamus activated by exposure to warm and cold temperatures and may aid in the functional identification of central thermoregulatory pathways.

Introduction

The role of the central nervous system (CNS) in thermoregulation is well established, but the organization of central neuronal pathways responsible for the maintenance of body temperature within narrow limits remains unclear. Behavioural and autonomic responses to exposure to warm and cold environments vary in different species, suggesting the possibility that different central pathways may be responsible for generating different thermoregulatory responses. However, there are specific regions in the mammalian CNS which are established as central thermoregulatory sites, most notably the hypothalamus 2, 10.

It has been established using local heating and cooling 2, 10, 14, 15, 16, electrophysiological recording 3, 9, 12 and 2-deoxyglucose autoradiography [22] that the preoptic area and anterior hypothalamus (PAOH) contain neurons that change their activity in response to temperature changes. These changes are responsible for the behavioural and autonomic adjustments designed to maintain body temperature within a narrow range. In the hypothalamus, a number of areas are implicated in participating in specific thermoregulatory adjustments. These adjustments (and hypothalamic areas) include non-shivering thermogenesis that involves changes in the metabolism of brown adipose tissue or dietary-induced thermogenesis (ventromedial hypothalamus 6, 11, 24, 30), shivering (posterior hypothalamus [30]) and circadian thermoregulation (suprachiasmatic nucleus [4]).

We have recently used the technique of immunohistochemical detection of the nuclear protein Fos to define areas in the CNS that are activated by stimulation of peripheral nerves 18, 19. Fos is rapidly and transiently expressed in neurons following synaptic activation (see [21]) and can provide detailed information regarding the locations of neurons involved in specific physiological reflexes [18]. Previous studies have investigated the distribution of Fos in the hypothalamus of cold-exposed rat pups [13] and [14C]-deoxyglucose uptake in the hypothalamus of warm- and cold-exposed unanaesthetized rats [27].

In this study we have investigated the hypothalamic distribution of Fos in response to changes in environmental temperature in anaesthetized adult rats in order to investigate the distribution of Fos in the hypothalamus in the absence of thermoregulatory behaviour. Urethane anaesthesia was chosen for three reasons. First, urethane rapidly induces a surgical plane of anaesthesia that remains stable over hours without the necessity for supplemental doses, and without changes in the plane of anaesthesia [17]. Second, urethane anaesthesia has been demonstrated not to affect the activity and responsiveness of hypothalamic neurons and to preserve the centrally organized reflex responses to peripheral stimuli [17]. Finally, as urethane is widely used in studies of central thermoregulatory processes (e.g., 1, 6, 8, 9, 11, 14, 15, 24, 29, 30), urethane was chosen to facilitate the interpretation of these results in comparison with the results of previous studies.

Section snippets

Exposure to warm and cold environments

Experiments were done in 36 adult male Wistar rats (250–350 g) anaesthetized with urethane (1.4 g/kg intraperitoneal, plus a single 0.2 g supplement within 5–10 min of the original urethane injection as required). Before the experiments all animals were housed for at least 48 h in a light- (12 h on/12 h off) and temperature- (ambient temperature 23°C) controlled room and had free access to food and water. At 1300 h on the day of the experiment, rats were anaesthetized and placed in individual

Results

For comparison of hypothalamic thermoregulatory sites identified in previous studies the nomenclature used to identify hypothalamic sites containing Fos in this study is based on that used in Paxinos and Watson [23]. A summary of the hypothalamic areas containing Fos, and a representation of the average number of labelled neurons in each area, in each temperature group, is given in Fig. 1.

Line drawings are provided in fig. 2, fig. 3, fig. 4, fig. 5, fig. 6, fig. 7 showing the average

Discussion

The results of this study suggest that a number of discrete hypothalamic nuclei participate in thermoregulatory processes. In most cases, these hypothalamic areas have been previously identified as having a role in the autonomic and behavioral responses to changes in environmental temperature. However, some novel findings are reported based on the distribution of Fos in the hypothalamus, which may resolve some of the controversy regarding hypothalamic involvement in thermoregulation. The

Acknowledgements

I thank Mr. B. K. Stephenson for technical assistance and gratefully acknowledge the support of the Heart and Stroke Foundation of Canada.

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