Kazuhiro Nakamura

Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonsh

Sympathetic premotor neurons directly control sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column (IML) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. The rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. Here, we show that these medullary r

Fever is the widely known hallmark of disease and is induced by the action of the nervous system. It is generally accepted that prostaglandin (PG) E(2) is produced in response to immune signals and then acts on the preoptic area (POA), which triggers the stimulation of the sympathetic system, resulting in the production of fever. Actually, the EP3 subtype of PGE receptor, which is essential for the induction of fever, is known to be localized in POA neurons. However, the neural pathway mediating

Afferent neural transmission of temperature sensation from skin thermoreceptors to the central thermoregulatory system is important for the defense of body temperature against environmental thermal challenges. Here, we report a thermosensory pathway that triggers physiological heat-defense responses to elevated environmental temperature. Using in vivo electrophysiological and anatomical approaches in the rat, we found that neurons in the dorsal part of the lateral parabrachial nucleus (LPBd) glu

Control of thermoregulatory effectors by the autonomic nervous system is a critical component of rapid cold-defense responses, which are triggered by thermal information from the skin. However, the central autonomic mechanism driving thermoregulatory effector responses to skin thermal signals remains to be determined. Here, we examined the involvement of several autonomic brain regions in sympathetic thermogenic responses in brown adipose tissue (BAT) to skin cooling in urethane-chloralose-anest

Shivering is a remarkable somatomotor thermogenic response that is controlled by brain mechanisms. We recorded EMGs in anaesthetized rats to elucidate the central neural circuitry for shivering and identified several brain regions whose thermoregulatory neurons comprise the efferent pathway driving shivering responses to skin cooling and pyrogenic stimulation. We simultaneously monitored parameters from sympathetic effectors: brown adipose tissue (BAT) temperature for non-shivering thermogenesis

Protein tyrosine phosphorylation was examined after T cells were exposed to oxidative stress in vitro to investigate the possible involvement of redox regulation in T-cell signaling. Oxidative reagents such as hydrogen peroxide (H2O2) and diamide, which oxidize the free sulfhydryl groups in the cells, markedly induced tyrosine phosphorylation of multiple cellular proteins, especially a 55-kDa protein, of cultured peripheral blood T lymphocytes (PBL blasts). The 55-kDa molecule phosphorylated by

The prostaglandin EP3 receptor (EP3R) subtype is believed to mediate large portions of diverse physiologic actions of prostaglandin E2 in the nervous system. However, the distribution of EP3R protein has not yet been unveiled in the peripheral or central nervous systems. The authors raised a polyclonal antibody against an amino-terminal portion of rat EP3R that recognized specifically the receptor protein. In this study, immunoblotting analysis with this antibody showed several immunoreactive ba

The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to

We recently identified a somatosensory pathway that transmits temperature information from the skin to a median subregion of the preoptic area (POA), a thermoregulatory centre. Here, we investigated in vivo the local neuronal circuit in the rat POA that processes the thermosensory information and outputs thermoregulatory effector signals. Skin cooling-evoked increases in sympathetic thermogenesis in brown adipose tissue, in metabolism and in heart rate were reversed by inhibition of neurons in t

p62/Sequestosome 1 is a scaffold protein involved in the regulation of autophagy, trafficking of proteins to the proteasome, and activation of NF-kappaB. p62 encodes an N-terminal PB1 domain in addition to the ZZ domain, TRAF6-binding domain, LC3 interaction region, and ubiquitin-associated domain, each critical for the physiological function of p62. PB1 domains have a beta-grasp topology where the front end of one PB1 domain binds the back end of a second PB1 domain. The p62 PB1 domain homodime

Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5-HT. Two isoforms (TPH1 and TPH2) having tryptophan hydroxylating activity were identified. Association studies have revealed possible TPH1 involvement in psychiatric conditions and behavioral traits. However, TPH1 mRNA was reported to be mainly expressed in the pineal gland and the periphery and to be barely dete