The Experts below are selected from a list of 5805 Experts worldwide ranked by ideXlab platform
J Orofino - One of the best experts on this subject based on the ideXlab platform.
-
Periodontal and gastric convergences within the hypothalamic Ventromedial Nucleus area--single unit study on anesthetized rats.
Behavioural brain research, 1995Co-Authors: M Trub, N Mei, J OrofinoAbstract:Unitary activities were recorded in the Ventromedial Nucleus of the hypothalamus (VHM) of anesthetized rats. Cells responding to periodontal stimulation (100-200 g disto-mesial traction applied to an upper incisive) were selected. The effects of gastric stimulation (2-5 ml distension) were then investigated. Out of the 40 cells activated (22 cells) or inhibited (18 cells) by periodontal stimulation, only seventeen were influenced by gastric stimulation. Eight of them responded in the same way and nine in the opposite way. Unlike the periodontal stimulation, which elicited specific spatio-temporal patterns, the gastric stimulation had only weak effects. These data nevertheless demonstrate that periodontal-gastric convergences exist in the VHM Nucleus, which is consistent with the role previously ascribed to this area in alimentary behaviour.
-
Periodontal and gastric convergences within the hypothalamic Ventromedial Nucleus area — single unit study on anesthetized rats
Behavioural Brain Research, 1995Co-Authors: M Trub, Mei N, J OrofinoAbstract:Unitary activities were recorded in the Ventromedial Nucleus of the hypothalamus (VHM) of anesthetized rats. Cells responding to periodontal stimulation (100-200 g disto-mesial traction applied to an upper incisive) were selected. The effects of gastric stimulation (2-5 ml distension) were then investigated. Out of the 40 cells activated (22 cells) or inhibited (18 cells) by periodontal stimulation, only seventeen were influenced by gastric stimulation. Eight of them responded in the same way and nine in the opposite way. Unlike the periodontal stimulation, which elicited specific spatio-temporal patterns, the gastric stimulation had only weak effects. These data nevertheless demonstrate that periodontal-gastric convergences exist in the VHM Nucleus, which is consistent with the role previously ascribed to this area in alimentary behaviour.
Sonoko Ogawa - One of the best experts on this subject based on the ideXlab platform.
-
silencing of estrogen receptor α in the Ventromedial Nucleus of hypothalamus leads to metabolic syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Sergei Musatov, Donald W. Pfaff, Walter W Chen, Michael G Kaplitt, Charles V Mobbs, Xuejun Yang, Deborah J Clegg, Sonoko OgawaAbstract:Estrogen receptor α (ERα) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that a disruption of ERα signaling in ERα knockout (ERKO) mice leads to an obese phenotype, the sites of estrogen action and mechanisms underlying this phenomenon are still largely unknown. In the present study, we exploited RNA interference mediated by adeno-associated viral vectors to achieve focused silencing of ERα in the Ventromedial Nucleus of the hypothalamus, a key center of energy homeostasis. After suppression of ERα expression in this Nucleus, female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by obesity, hyperphagia, impaired tolerance to glucose, and reduced energy expenditure. This phenotype persisted despite normal ERα levels elsewhere in the brain. Although an increase in food intake preceded weight gain, our data suggest that a leading factor of obesity in this model is likely a decline in energy expenditure with all three major constituents being affected, including voluntary activity, basal metabolic rate, and diet-induced thermogenesis. Together, these findings indicate that ERα in the Ventromedial Nucleus of the hypothalamus neurons plays an essential role in the control of energy balance and the maintenance of normal body weight.
-
Silencing of estrogen receptor α in the Ventromedial Nucleus of hypothalamus leads to metabolic syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Sergei Musatov, Donald W. Pfaff, Walter W Chen, Michael G Kaplitt, Charles V Mobbs, Xuejun Yang, Deborah J Clegg, Sonoko OgawaAbstract:Estrogen receptor α (ERα) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that a disruption of ERα signaling in ERα knockout (ERKO) mice leads to an obese phenotype, the sites of estrogen action and mechanisms underlying this phenomenon are still largely unknown. In the present study, we exploited RNA interference mediated by adeno-associated viral vectors to achieve focused silencing of ERα in the Ventromedial Nucleus of the hypothalamus, a key center of energy homeostasis. After suppression of ERα expression in this Nucleus, female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by obesity, hyperphagia, impaired tolerance to glucose, and reduced energy expenditure. This phenotype persisted despite normal ERα levels elsewhere in the brain. Although an increase in food intake preceded weight gain, our data suggest that a leading factor of obesity in this model is likely a decline in energy expenditure with all three major constituents being affected, including voluntary activity, basal metabolic rate, and diet-induced thermogenesis. Together, these findings indicate that ERα in the Ventromedial Nucleus of the hypothalamus neurons plays an essential role in the control of energy balance and the maintenance of normal body weight.
-
rnai mediated silencing of estrogen receptor α in the Ventromedial Nucleus of hypothalamus abolishes female sexual behaviors
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Donald W. Pfaff, Sergei Musatov, Walter W Chen, Michael G Kaplitt, Sonoko OgawaAbstract:Estrogen receptor α (ERα) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ERα knockout mice advanced our knowledge of ERα functions, gene deletion using this method is global and potentially confounded by developmental consequences. To achieve a site-specific knockdown of ERα in the normally developed adult brain, we have generated an adeno-associated virus vector expressing a small hairpin RNA targeting ERα. After bilateral injection of this vector into the hypothalamic Ventromedial Nucleus in ovariectomized female mice, expression levels of ERα as well as the estrogen-inducible progesterone receptor were profoundly reduced despite the continued presence of this receptor elsewhere in the brain. Functionally, silencing of ERα in the Ventromedial Nucleus abolished female proceptive and receptive sexual behaviors while enhancing rejection behavior. These results provide evidence that adeno-associated virus-mediated long-term knockdown of genes can be used to delineate their effects on complex behaviors in discrete brain regions.
Donald W. Pfaff - One of the best experts on this subject based on the ideXlab platform.
-
silencing of estrogen receptor α in the Ventromedial Nucleus of hypothalamus leads to metabolic syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Sergei Musatov, Donald W. Pfaff, Walter W Chen, Michael G Kaplitt, Charles V Mobbs, Xuejun Yang, Deborah J Clegg, Sonoko OgawaAbstract:Estrogen receptor α (ERα) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that a disruption of ERα signaling in ERα knockout (ERKO) mice leads to an obese phenotype, the sites of estrogen action and mechanisms underlying this phenomenon are still largely unknown. In the present study, we exploited RNA interference mediated by adeno-associated viral vectors to achieve focused silencing of ERα in the Ventromedial Nucleus of the hypothalamus, a key center of energy homeostasis. After suppression of ERα expression in this Nucleus, female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by obesity, hyperphagia, impaired tolerance to glucose, and reduced energy expenditure. This phenotype persisted despite normal ERα levels elsewhere in the brain. Although an increase in food intake preceded weight gain, our data suggest that a leading factor of obesity in this model is likely a decline in energy expenditure with all three major constituents being affected, including voluntary activity, basal metabolic rate, and diet-induced thermogenesis. Together, these findings indicate that ERα in the Ventromedial Nucleus of the hypothalamus neurons plays an essential role in the control of energy balance and the maintenance of normal body weight.
-
Silencing of estrogen receptor α in the Ventromedial Nucleus of hypothalamus leads to metabolic syndrome
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Sergei Musatov, Donald W. Pfaff, Walter W Chen, Michael G Kaplitt, Charles V Mobbs, Xuejun Yang, Deborah J Clegg, Sonoko OgawaAbstract:Estrogen receptor α (ERα) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that a disruption of ERα signaling in ERα knockout (ERKO) mice leads to an obese phenotype, the sites of estrogen action and mechanisms underlying this phenomenon are still largely unknown. In the present study, we exploited RNA interference mediated by adeno-associated viral vectors to achieve focused silencing of ERα in the Ventromedial Nucleus of the hypothalamus, a key center of energy homeostasis. After suppression of ERα expression in this Nucleus, female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by obesity, hyperphagia, impaired tolerance to glucose, and reduced energy expenditure. This phenotype persisted despite normal ERα levels elsewhere in the brain. Although an increase in food intake preceded weight gain, our data suggest that a leading factor of obesity in this model is likely a decline in energy expenditure with all three major constituents being affected, including voluntary activity, basal metabolic rate, and diet-induced thermogenesis. Together, these findings indicate that ERα in the Ventromedial Nucleus of the hypothalamus neurons plays an essential role in the control of energy balance and the maintenance of normal body weight.
-
rnai mediated silencing of estrogen receptor α in the Ventromedial Nucleus of hypothalamus abolishes female sexual behaviors
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Donald W. Pfaff, Sergei Musatov, Walter W Chen, Michael G Kaplitt, Sonoko OgawaAbstract:Estrogen receptor α (ERα) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ERα knockout mice advanced our knowledge of ERα functions, gene deletion using this method is global and potentially confounded by developmental consequences. To achieve a site-specific knockdown of ERα in the normally developed adult brain, we have generated an adeno-associated virus vector expressing a small hairpin RNA targeting ERα. After bilateral injection of this vector into the hypothalamic Ventromedial Nucleus in ovariectomized female mice, expression levels of ERα as well as the estrogen-inducible progesterone receptor were profoundly reduced despite the continued presence of this receptor elsewhere in the brain. Functionally, silencing of ERα in the Ventromedial Nucleus abolished female proceptive and receptive sexual behaviors while enhancing rejection behavior. These results provide evidence that adeno-associated virus-mediated long-term knockdown of genes can be used to delineate their effects on complex behaviors in discrete brain regions.
-
acute estrogen potentiates excitatory responses of neurons in rat hypothalamic Ventromedial Nucleus
Brain Research, 2005Co-Authors: Lee-ming Kow, A Easton, Donald W. PfaffAbstract:In a previous behavioral study, brief application of a membrane-limited estrogen to neurons in rat hypothalamic Ventromedial Nucleus (VMN) facilitated lordosis behavior-inducing genomic actions of estrogen. Here, electrophysiological recordings from single neurons were employed to characterize these membrane-initiated actions. From rat hypothalamic slices, electrical activity was recorded from neurons in the ventrolateral VMN, the cell group crucial for estrogen induction of lordosis. In addition to the resting activity, neuronal responses to histamine (HA) and N-methyl-d-aspartate (NMDA) were also recorded before, during, and after a brief (10–15 min) application of estradiol (E, 10 nM). These two transmitters were chosen because their actions are mediated by different mechanisms: HA through G protein-coupled receptors and NMDA by ligand-activated ion channels. Vehicle applications did not affect either resting activity or neuronal responses. In contrast, acute E exposure modulated neuronal responses to transmitters, with no significant effect on the resting activity. It potentiated excitatory responses to HAs (20 out of 48 cells tested) and to NMDA (10 out of 19 cells), but attenuated inhibitory responses to HA (3 out of 6 units). Both of these hormonal actions would increase VMN neuronal excitation. In separate experiments, neuronal excitation was found to be suppressed by anesthetics, which would block E's induction of lordosis when administered at the time of estrogen application. These data are consistent with the notion that increasing electrical excitation of VMN neurons can be a mechanism by which acute E exposure facilitates the lordosis-inducing genomic actions of estrogens.
-
Ultrastructural evidence for enkephalin mediated disinhibition in the Ventromedial Nucleus of the hypothalamus.
Journal of chemical neuroanatomy, 2001Co-Authors: Kathryn G. Commons, Donald W. PfaffAbstract:The Ventromedial Nucleus of the hypothalamus (VMN) regulates the estrogen-dependent appearance of female mating behavior, lordosis. Accumulating evidence suggests that estrogen might exert its control over lordosis by acting, in part, on neurons that contain enkephalin in the VMN. The expression of the enkephalin precursor gene is robustly stimulated by estrogen and is correlated with the later appearance of lordosis. GABA has also been implicated as an important neurotransmitter for the appearance of lordosis. Because enkephalin is thought to act in several brain areas to modulate the activity of GABAergic neurons, we studied the ultrastructural morphology and relationship between neurons containing these neurochemicals using dual-labeling immunocytochemistry in ovariectornized rats, half of which received estrogen replacement. Immunolabeling for enkephalin was almost always detected within axon terminals (695 axonal profiles sampled), while GABA immunoreactivity was more often localized to cell bodies and dendrites (191 profiles), than to axons (63 profiles). Axon terminals containing enkephalin immunolabeling provided a major innervation to soma or dendrites containing GABA. That is, over one third (94/245) of the axon terminals in contact with GABA-immunoreactive dendrites contained enkephalin. Furthermore, these GABA-immunoreactive dendrites accounted for a fifth of the somatodendritic processes associated with enkephalin-containing axon terminals. These findings support the hypothesis that enkephalin may act in the VMN by inhibiting GABAergic neurons, which could result in the disinhibition of neural circuits relevant for lordosis.
M Trub - One of the best experts on this subject based on the ideXlab platform.
-
Periodontal and gastric convergences within the hypothalamic Ventromedial Nucleus area--single unit study on anesthetized rats.
Behavioural brain research, 1995Co-Authors: M Trub, N Mei, J OrofinoAbstract:Unitary activities were recorded in the Ventromedial Nucleus of the hypothalamus (VHM) of anesthetized rats. Cells responding to periodontal stimulation (100-200 g disto-mesial traction applied to an upper incisive) were selected. The effects of gastric stimulation (2-5 ml distension) were then investigated. Out of the 40 cells activated (22 cells) or inhibited (18 cells) by periodontal stimulation, only seventeen were influenced by gastric stimulation. Eight of them responded in the same way and nine in the opposite way. Unlike the periodontal stimulation, which elicited specific spatio-temporal patterns, the gastric stimulation had only weak effects. These data nevertheless demonstrate that periodontal-gastric convergences exist in the VHM Nucleus, which is consistent with the role previously ascribed to this area in alimentary behaviour.
-
Periodontal and gastric convergences within the hypothalamic Ventromedial Nucleus area — single unit study on anesthetized rats
Behavioural Brain Research, 1995Co-Authors: M Trub, Mei N, J OrofinoAbstract:Unitary activities were recorded in the Ventromedial Nucleus of the hypothalamus (VHM) of anesthetized rats. Cells responding to periodontal stimulation (100-200 g disto-mesial traction applied to an upper incisive) were selected. The effects of gastric stimulation (2-5 ml distension) were then investigated. Out of the 40 cells activated (22 cells) or inhibited (18 cells) by periodontal stimulation, only seventeen were influenced by gastric stimulation. Eight of them responded in the same way and nine in the opposite way. Unlike the periodontal stimulation, which elicited specific spatio-temporal patterns, the gastric stimulation had only weak effects. These data nevertheless demonstrate that periodontal-gastric convergences exist in the VHM Nucleus, which is consistent with the role previously ascribed to this area in alimentary behaviour.
Michio Takahashi - One of the best experts on this subject based on the ideXlab platform.
-
The rostral ventrolateral medulla mediates suppression of the circulatory system by the Ventromedial Nucleus of the hypothalamus
Brain research, 1996Co-Authors: Michiru Hirasawa, M Nishihara, Michio TakahashiAbstract:We recently reported that a train of episodic neural discharges within the Ventromedial Nucleus of the hypothalamus (VMH) associated with suppression of the circulatory system had been determined by monitoring multiple unit activity (MUA). Abrupt increases in neural activity (MUA volleys; 1 to 4 min in duration) accompanied transient decreases in heart rate (HR) and blood pressure (BP), and showed circadian rhythm, occurring every 15 to 30 min in the light phase but seldom in the dark phase. The present study was aimed to determine if neurons in the vasomotor area of the rostral ventrolateral medulla (RVL) are involved in this VMH-induced cardiovascular suppression. MUAs of the VMH and RVL were monitored simultaneously with HR and BP in urethane-anesthetized rats. In synchrony with each MUA volley in the VMH, spontaneous activity of RVL neurons significantly decreased, as well as HR and BP. These RVL neurons are most likely vasomotor neurons because MUA of the RVL was attenuated by baroreceptor reflex activation, and electrical stimulation of these cells through the MUA recording electrodes produced pressor responses. These data suggest that VMH neurons that show a train of episodic discharges suppress the circulatory system at least in part by inhibiting the excitability of vasomotor neurons in the RVL.
-
Concomitant regulation of running activity and metabolic change by the Ventromedial Nucleus of the hypothalamus
Brain Research, 1994Co-Authors: K Narita, M Nishihara, Michio TakahashiAbstract:Abstract The aim of this study was to elucidate the involvement of kainate (KA) type glutaminergic, GABAergic and adrenergic receptors in the Ventromedial Nucleus of the hypothalamus (VMH) in inducing running activity and metabolic adaptations. Injection of either KA or bicuculline methiodide (BM), a GABA A receptor antagonist, into the VMH of conscious rats resulted in an increase in plasma glucose, norepinephrine, epinephrine and corticosterone, as well as running activity. KA or BM increased plasma glucose and catecholamines even under urethane anesthesia. Co-injection of either α- or β-adrenergic receptor antagonist, i.e. phentolamine or timolol, respectively, with KA into the VMH of conscious rats elicited only a slight increase in plasma glucose and catecholamines, though it successfully induced hyper-running. However, plasma corticosterone was higher in the animals injected with adrenergic blockers, suggesting that an insufficient supply of energy substrates would enhance the activity of the hypothalamo-pituitary-adrenal system. We conclude that: (1) KA type glutaminergic and GABAergic receptors in the VMH are involved in regulating running activity and the sympathetic nervous system; (2) the brain noradrenergic system may mediate the KA action on the sympathetic nervous system.
