Participation of preoptic area TRPV4 ion channel in regulation of body temperature

Transient receptor potential vanilloid 4 (TRPV4) ion channel is a non-selective cation channel and its role in cutaneous thermosensation is emerging. It is expressed in many areas of the brain including the preoptic area (POA)/anterior hypothalamus which is the key neural site for thermoregulation. The present study was conducted to find out the role of TRPV4 ion channel in the POA in thermoregulation. Rats preimplanted with guide cannulae with indwelling styli 2.0 mm above the POA received TRPV4 agonist/antagonist/isotonic saline injections bilaterally in the POA using an injector cannula in three separate groups of six rats each. Body temperature (Tb) was recorded telemetrically by preimplanted radio transmitter in the peritoneal cavity. The injection of TRPV4 agonist (GSK1016790A) in the POA decreased Tb while its antagonist (RN1734) increased Tb. Immunohistochemical localization showed presence of TRPV4 ion channel in the POA. The results of the present study suggest that TRPV4 ion channels in the POA may play an important role in thermoregulation.     

Effects of electrical stimulation of ventral septal area on firing rates of pyrogen-treated thermosensitive neurons in preoptic anterior hypothalamus from rabbits

Although there is considerable evidence supporting that fever evolved as a host defense response, it is important that the rise in body temperature would not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified. Endogenous antipyretics attenuate fever by influencing the thermoregulatory neurons in the preoptic anterior hypothalamus (POAH) and in adjacent septal areas including ventral septal area (VSA). Our previous study showed that intracerebroventricular (I.C.V.) injection of interleukin-1beta (IL-1beta) affected electrophysiological activities of thermosensitive neurons in VSA regions, and electrical stimulation of POAH reversed the effect of IL-1beta. To further investigate the functional electrophysiological connection between POAH and VSA and its mechanisms in thermoregulation, the firing rates of thermosensitive neurons in POAH of forty-seven unit discharge were recorded by using extracellular microelectrode technique in New Zealand white rabbits. Our results show that the firing rates of the warm-sensitive neurons decreased significantly and those of the cold-sensitive neurons increased in POAH when the pyrogen (IL-1beta) was injected I.C.V. The effects of IL-1beta on firing rates in thermosensitive neurons of POAH were reversed by electrical stimulation of VSA. An arginine vasopressin (AVP) V1 antagonist abolished the regulatory effects of VSA on the firing rates in thermosensitive neurons of POAH evoked by IL-1beta. However, an AVP V2 antagonist had no effects. These data indicated that VSA regulates the activities of the thermosensitive neurons of POAH through AVP V1 but not AVP V2 receptor.     

Role of striatal serotonin2A and serotonin2C receptor subtypes in the control of in vivo dopamine outflow in the rat striatum

This study investigated, using in vivo microdialysis in the striatum of freely moving rats, the role of striatal serotonin2A (5-HT2A) and 5-HT2C receptor subtypes in the modulation of dopamine (DA) and 3, 4-dihydroxyphenylacetic acid (DOPAC) outflow, both in basal conditions and under activation induced by subcutaneous administration of 0.01 mg/kg haloperidol. The different 5-HT2 agents used were applied intrastriatally at a 1 microM concentration through the microdialysis probe. Basal DA efflux was enhanced (27%) by the 5-HT2A/2B/2C agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) and reduced (-30%) by the 5-HT2B/2C antagonist SB 206553. It was unaffected by infusion of the 5-HT2A antagonist SR 46349B. The effect of DOI was abolished by SB 206553 but not modified by SR 46349B. Haloperidol-stimulated DA efflux (65-70%) was reduced by both SR 46349B (-32%) and the 5-HT2A/2B/2C antagonist ritanserin (-30%) but not affected by SB 206553. Conversely, the effect of haloperidol was potentiated (22%) when DOI was coperfused with SB 206553. Also, haloperidol-stimulated DOPAC outflow (40-45%) was reduced (-20%) by SR 46349B and potentiated (25%) by the combination of SB 206553 with DOI. These results indicate that striatal 5-HT2A receptors, probably through activation of DA synthesis, positively modulate DA outflow only under activated conditions. In contrast, striatal 5-HT2C receptors exert a facilitatory control on basal DA efflux, which appears to be both tonic and phasic.     

Neuropeptide Y perfused in the preoptic area of rats shifts extracellular efflux of dopamine,norepinephrine and serotonin during hypothermia and feeding

This study examined the localized action of neuropeptide Y (NPY) on monoamine transmitter activity in the hypothalamus of the unrestrained rat as this peptide induced hypothermia, spontaneous feeding or both responses simultaneously. A guide tube was implanted in the anterior hypothalamic pre-optic area (AH/POA) of Sprague-Dawley rats. Then either control CSF vehicle or NPY in a dose of either 100 ng/μl or 250 ng/μl was perfused by push-pull cannulae in this structure in the fully sated, normothermic rat. Successive perfusions were carried out at a rate of 20 μl/min for 6.0 min with an interval of 6.0 min elapsing between each. Samples of perfusate were assayed by HPLC for their levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their respective metabolites. Whereas control CSF was without effect on body temperature (T_b) or feeding, repeated perfusions of NPY over 3.0 hr caused dose—dependent eating from 4 to 39 g of food, hypothermia of 0.9 to 2.3°C or both responses concurrently. As the rats consumed 11–39 g of food, the efflux of NE, MHPG, DOPAC and 5-HT was enhanced significantly, whereas during the fall in T_b the efflux of NE, DOPAC and 5-HIAA from the AH/POA increased. When the T_b of the rat declined simultaneously with eating behavior, the levels in perfusate of DOPAC and HVA increased significantly while MHPG declined. During perfusion of the AH/POA with NPY the turnover of NE declined while DA and 5-HT turnover increased during hypothermia alone or when accompanied by feeding. These results demonstrate that the sustained elevation in NPY within the AH/POA causes a selective alteration in the activity of the neurotransmitters implicated in thermoregulation, satiety and hunger. These findings suggest that both DA and NE comprise intermediary factors facilitating the action of NPY on neurons involved in thermoregulatory and ingestive processes. The local activity of NPY on hypothalamic neurons apparently shifts the functional balance of serotonergic and catecholaminergic neurons now thought to play a primary role in the control of energy metabolism and caloric intake.     

Changes in body temperature and metabolic rate following microinjection of Met-enkephalinamide in the preoptic/anterior hypothalamus of rats

The effects of Met-enkephalinamide (MET-ENKamide) on brain temperature (Tb) and metabolic rate (MR) were assessed following direct administration into the preoptic/anterior hypothalamus (PO/AH) of freely moving rats. Bilateral microinjections of saline or MET-ENKamide (1-25 micrograms/microliter) were delivered through cannula guide tubes previously implanted in nine animals. Thiorphan, an enkephalinase inhibitor, was microinjected into the PO/AH of two of the animals. All injections were made remotely at an ambient temperature of 22 +/- 1 degree C in a volume of 1 microliter. Measurements of Tb (via a brain-dwelling thermistor) and MR were recorded continuously. The ability of naloxone to antagonize the effects of MET-ENKamide was investigated by fashioning a double-barreled injection cannula to fit within each guide tube; 1 microliter of saline or naloxone (1-10 micrograms) was delivered bilaterally into the PO/AH followed by 1 microliter of MET-ENKamide (25 micrograms) 5-10 min later. PO/AH administration of MET-ENKamide (1-25 micrograms) produced dose-dependent increases in Tb preceded by dose-dependent increases in MR, with a characteristic time course of approximately 30 min. Naloxone antagonized the rise in Tb and MR, either partially or completely, depending on dose. When administered alone, naloxone had no effect on Tb or MR. Microinjection of thiorphan (10 micrograms) into the PO/AH evoked increases in Tb and MR that were similar to those responses induced by MET-ENKamide. These results support a role for endogenous Met-enkephalin in the regulation of Tb in the rat.     

Effect of thermal tachypnoea and of its mechanical or pharmacological inhibition on hypothalamic temperature in the sheep

The abrupt inhibition of breathing in the panting sheep, by mechanical blockage of the nostrils or by the injection of noradrenaline or carbachol into a lateral cerebral ventricle, causes an immediate rise in hypothalamic temperature, followed by a rise in that of the carotid artery blood.

This confirms that evaporation from the surfaces of the upper respiratory tract has an immediate and local effect on brain temperature.

The significance of this relation in a species which controls its core temperature particularly well is discussed.     

Involvement of orexin-2 receptors in the ventral tegmental area and nucleus accumbens in the antinociception induced by the lateral hypothalamus stimulation in rats

Orexin, which is mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Both kinds of orexin-1 (Ox1) and orexin-2 (Ox2) receptors have been found at high density in the ventral tegmental area (VTA) and nucleus accumbens (NAc). However, the quantity of Ox1 receptors in the VTA is more than that in the NAc. Additionally, it seems that the functional interaction between the LH, VTA and NAc implicates pain processing and modulation. In this study, we tried to examine the involvement of Ox2 receptors in the NAc and VTA using tail-flick test as an animal model of acute pain following microinjection of effective dose of carbachol (125 nmol/0.5 μl saline) into the LH. In this set of experiments, different doses of TCS OX2 29 as an Ox2 receptor antagonist were microinjected into the VTA (1, 7 and 20 nmol/0.3 μl DMSO) and the NAc (2, 10, 20 and 40 nmol/0.5 μl DMSO) 5 min prior to carbachol administration. Administration of TCS OX2 29 into the VTA and NAc dose-dependently blocked intra-LH carbachol-induced antinociception. However, the inhibitory effect of TCS OX2 29 as an Ox2 receptor antagonist was more potent in the VTA than that in the NAc. It seems that VTA orexinergic receptors are more effective on LH stimulation-induced antinociception and the modulation of pain descending inhibitory system originated from the LH than those of the same receptors in the nucleus accumbens in rats.     

Effects of NMDA and non-NMDA ionotropic glutamate receptors in the medial preoptic area on body temperature in awake rats

Glutamate when microinjected at the medial preoptic area (mPOA) influences brain temperature (T_br) and body temperature (T_b) in rats. Glutamate and its various receptors are present at the mPOA. The aim of this study was to identify the contribution of each of the ionotropic glutamatergic receptors at the mPOA on changes in T_br and T_b in freely moving rats. Adult male Wistar rats (n=40) were implanted with bilateral guide cannula with indwelling styli above the mPOA. A telemetric transmitter was implanted at the peritoneum to record T_b and locomotor activity (LMA). A precalibrated thermocouple wire implanted near the hypothalamus was used to assess T_br. Specific agonist for each ionotropic glutamate receptor was microinjected into the mPOA and its effects on temperature and LMA were measured in the rats. The rats were also microinjected with the respective ionotropic receptor antagonists, 15 min prior to the microinjection of each agonist. Amongst amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA) and kainic acid, AMPA increased T_b and LMA when injected at the mPOA. Specific antagonists for AMPA receptors was able to attenuate this increase (p<0.005). Pharmacological blockade of NMDA was able to lower T_br only. Microinjection of kainic acid and its antagonist had no effect on the variables. The finding of the study suggests that activation of the AMPA receptors at the mPOA, leads to the rise in body temperature.     

北京平原造林后景观格局与热场环境的耦合分析

在人类积极的土地利用调控下(植树造林),研究景观格局变化对城乡热场环境的影响,可为今后的城市造林工程建设与优化提供参考,并为未来景观格局与热场环境的相关研究提供新视角.本研究以北京平原区百万亩造林项目为背景,运用遥感技术和地理信息系统,利用矩阵转移及耦合分析,评估平原造林对城市热场环境的实际作用,探究因城市造林工程引起的景观格局变化与城市地表温度变化的相关关系.结果表明: 北京平原造林工程后,森林和公园的面积比例分别增加了7.6%和0.5%;平原区有19.2%区域热场强度降低,其中,城郊有23.3%区域的热场强度减弱,但仍有23.5%的城市区域存在热场增强的情况;在城乡尺度上,森林和公园面积比例、森林和湿地的平均斑块面积(MPS)与地表亮温(LST)变化呈显著负相关;在城市市区,森林的面积加权平均形状指数(AWMSI)与LST变化呈显著正相关;在城郊区域,森林的MPS和AWMST与LST变化均呈显著负相关,而公园则相反.北京实施平原造林工程后,增加的城市森林和公园对城市热场的缓解有一定作用,但范围有限,主要集中在城郊区的造林点周围,且森林与湿地越集中,越有利于热场的缓解;受研究粒度、时相、地形、人类活动等因素影响,土地利用结构调控引起的景观格局变化与地表温度变化之间存在非线性相关.