Effects of thyrotrophic-releasing hormone (TRH) on thermoregulation in the rat

At ambient temperatures (Ta) of both 8 and 22 degrees C, intraventricular administration of TRH (10-80 microgram) produced a dose-dependent hypothermia in rats. The hypothermia was due to both decreased metabolic heat production and cutaneous vasodilatation. In contrast, at 30 degrees C Ta, TRH increased metabolic heat production (due to behavioral excitation) and led to hyperthermia.     

Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase

Cellular growth and proliferation are coordinated during organogenesis. Misregulation of these processes leads to pathological conditions such as cancer. Tuberous sclerosis (TSC) is a benign tumour syndrome caused by mutations in either TSC1 or TSC2 tumour suppressor genes. Studies in Drosophila and other organisms have identified TSC signalling as a conserved pathway for growth control. Activation of the TSC pathway is mediated by Rheb (Ras homologue enriched in brain), a Ras superfamily GTPase. Rheb is a direct target of TSC2 and is negatively regulated by its GTPase-activating protein activity. However, molecules required for positive regulation of Rheb have not been identified. Here we show that a conserved protein, translationally controlled tumour protein (TCTP), is an essential new component of the TSC-Rheb pathway. Reducing Drosophila TCTP (dTCTP) levels reduces cell size, cell number and organ size, which mimics Drosophila Rheb (dRheb) mutant phenotypes. dTCTP is genetically epistatic to Tsc1 and dRheb, but acts upstream of dS6k, a downstream target of dRheb. dTCTP directly associates with dRheb and displays guanine nucleotide exchange activity with it in vivo and in vitro. Human TCTP (hTCTP) shows similar biochemical properties compared to dTCTP and can rescue dTCTP mutant phenotypes, suggesting that the function of TCTP in the TSC pathway is evolutionarily conserved. Our studies identify TCTP as a direct regulator of Rheb and a potential therapeutic target for TSC disease.     

Effects of thyrotrophic-releasing hormone (TRH) on thermoregulation in the rat

Summary At ambient temperatures (T_a) of both 8 and 22°C, intraventricular administration of TRH (10–80 g) produced a dose-dependent hypothermia in rats. The hypothermia was due to both decreased metabolic heat production and cutaneous vasodilatation. In contrast, at 30°C T_a, TRH increased metabolic heat production (due to behavioral excitation) and led to hyperthermia.This work was supported by the grants from the National Science Council of Republic of China and the Pjing-Ling Neurological Foundation (VGH, Taipei, Taiwan).     

The effects of brain monoamine depletion on p-chlorophenyl-alanine-induced hypothermia.

I.p. administration of p-chlorophenylalanine produced a fall in rectal temperature in rats. The hypothermia was attenuated after pretreatment of the animals with 5,6-dihydroxytryptamine, but was unaffected after pretreatment of the animals with 6-hydroxydopamine.     

The hypothalamic somatostatinergic pathways mediate feeding behavior in the rat

The level of somatostatin in the hypothalamus was higher in satiated rats than in hungry rats. Elevating hypothalamic somatostatin levels by administering somatostatin into the hypothalamus produced a decrease in food intake, whereas lowering hypothalamic somatostatin levels by administering cysteamine into the peritoneal cavity produced an increase in food intake in rats.     

Haloperidol produces hypothermic effects in rats

Intraperitoneal administration of either haloperidol or chlorpromazine produced hypothermia both in the cold (8 degrees C) and at room temperature (22 degrees C). The hypothermia was brought about both by a decrease in metabolic heat production and an increase in the cutaneous temperature of tail and foot skin. However, at a higher temperature (29 degrees C), there were no changes in rectal temperature and other thermoregulatory responses.     

Effects of DL-propranolol on the thermoregulatory responses of rats at different ambient temperatures

Summary Direct administration of propranolol (100–400 g) into the lateral cerebral ventricle of rats produced a dose-dependent hypothermia at ambient temperatures (T_a) of 8 and 22°C. The hypothermia was due to decreased metabolism and cutaneous vasodilation. The hypothermia induced by propranolol was antagonized by pretreatment with isoproterenol (50 g).This work was supported by the grants from the National Science Council (Republic of China) and the Pjing-Ling Neurological Foundation (Veterans General Hospital). The authors are grateful to Mr C.C. Wei for generous support.     

Energy dysfunction in Huntington’s disease: insights from PGC-1α, AMPK, and CKB

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion in the Huntingtin (Htt) gene. When the number of CAG repeats exceeds 36, the translated polyglutamine-expanded Htt protein interferes with the normal functions of many types of cellular machinery and causes cytotoxicity. Clinical symptoms include progressive involuntary movement disorders, psychiatric signs, cognitive decline, dementia, and a shortened lifespan. The most severe brain atrophy is observed in the striatum and cortex. Besides the well-characterized neuronal defects, recent studies showed that the functions of mitochondria and several key players in energy homeostasis are abnormally regulated during HD progression. Energy dysregulation thus is now recognized as an important pathogenic pathway of HD. This review focuses on the importance of three key molecular determinants (peroxisome proliferator-activated receptor-γ coactivator-1α, AMP-activated protein kinase, and creatine kinase B) of cellular energy homeostasis and their possible involvement in HD pathogenesis.     

Haloperidol produces hypothermic effects in rats

Summary Intraperitoneal administration of either haloperidol or chlorpromazine produced hypothermia both in the cold (8° C) and at room temperature (22°C). The hypothermia was brought about both by a decrease in metabolic heat production and an increase in the cutaneous temperature of tail and foot skin. However, at a higher temperature (29°C), there were no changes in rectal temperature and other thermoregulatory responses.The work reported here was supported by grants from the National Science Council of Republic of China and J. Aron Charitable Foundation (New York, N.Y.). The authors are grateful to Dr C.Y. Chai for his advice during the experimentation. The generous support of Dr C.J. Shih was much appreciated by the authors. Also, we thank Dr C.D. Bloomer (Smith, Kline and French Co.) for the supply of chlorpromazine.     

The effects of brain monoamine depletion on p-chlorophenyl-alanine-induced hypothermia

Summary I.p. administration of p-chlorophenylalanine produced a fall in rectal temperature in rats. The hypothermia was attenuated after pretreatment of the animals with 5,6-dihydroxytryptamine, but was unaffected after pretreatment of the animals with 6-hydroxydopamine.This work was supported by grants from the National Science Council (Republic of China) and J. Aron Charitable Foundation (USA). The authors are grateful to Dr C.Y. Chai, Dr T.H. Yin, Dr H.H. Lu and Mr C.C. Wei for their advice and support.