Activation of 5-Hydroxytryptamine 1A Receptors Suppresses the Cardiovascular Response Evoked From the Dorsomedial Hypothalamic Nucleus

Neurons within the dorsomedial hypothalamic nucleus (DMH) and perifornical area (PeF), which lie within the classic hypothalamic defense area, subserve the cardiovascular response to psychological stress. Previous studies have shown that electrical stimulation of the hypothalamic defense area causes inhibition of the cardiac and (in some cases) sympathetic components of the baroreceptor reflex. In contrast, naturally evoked psychological stress does not appear to be associated with such inhibition. In this study, we tested the effect of specific activation of neurons within the DMH and PeF on the baroreflex control of renal sympathetic nerve activity and heart rate in urethane-anesthetized rats. Microinjection of bicuculline (a GABAA receptor antagonist) into the DMH caused dose-dependent increases in heart rate and renal sympathetic activity, shifted the baroreflex control of both variables to higher levels (i.e., increased the upper and lower plateaus of the baroreflex function curves, and increased the threshold, midpoint, and saturation levels of mean arterial pressure). The maximum gain of the sympathetic component of the baroreflex was also increased, while that of the cardiac component was not significantly changed. Increases in the midpoint were very similar in magnitude to the evoked increases in baseline mean arterial pressure. Microinjection of bicuculline into the PeF evoked very similar effects. The results indicate that disinhibition of neurons in the DMH/PeF region not only increases sympathetic vasomotor activity and heart rate but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure.

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Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.6.h2891 ◽

2001 ◽

Vol 280 (6) ◽

pp. H2891-H2901 ◽

Cited By ~ 137

Author(s):

M. A. P. Fontes ◽

T. Tagawa ◽

J. W. Polson ◽

S.-J. Cavanagh ◽

R. A. L. Dampney

Keyword(s):

Arterial Pressure ◽

Sympathetic Nerve Activity ◽

Nucleus Tractus Solitarius ◽

Cardiovascular Response ◽

Ventrolateral Medulla ◽

Hypothalamic Nucleus ◽

Descending Pathways ◽

Renal Sympathetic Nerve Activity ◽

Dorsomedial Hypothalamic Nucleus ◽

Renal Sympathetic

Physiological and anatomic methods were used to determine whether neurons in the rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), or hypothalamic paraventricular nucleus (PVN) mediate the cardiovascular response evoked from the dorsomedial hypothalamic nucleus (DMH), which is believed to play a key role in mediating responses to stress. In urethane-anesthetized rats, activation of neurons in the DMH by microinjection of bicuculline resulted in a large increase in arterial pressure, heart rate, and renal sympathetic nerve activity. The pressor and sympathoexcitatory responses, but not the tachycardic response, were greatly reduced after bilateral muscimol injections into the RVLM even when baseline arterial pressure was maintained at a constant level. These responses were not reduced by muscimol injections into the PVN or NTS. Retrograde tracing experiments identified many neurons in the DMH that projected directly to the RVLM. The results indicate that the vasomotor and cardiac components of the response evoked from the DMH are mediated by pathways that are dependent and independent, respectively, of neurons in the RVLM.

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Faculty Opinions recommendation of The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1022755.367932 ◽

2006 ◽

Author(s):

Joel Elmquist

Keyword(s):

Circadian Rhythms ◽

Hypothalamic Nucleus ◽

Dorsomedial Hypothalamic Nucleus

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Assessing the treatment of cannabidiolic acid methyl ester: a stable synthetic analogue of cannabidiolic acid on c-Fos and NeuN expression in the hypothalamus of rats

Journal of Cannabis Research ◽

10.1186/s42238-021-00081-1 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Eric Murillo-Rodríguez ◽

Diana Millán-Aldaco ◽

Gloria Arankowsky-Sandoval ◽

Tetsuya Yamamoto ◽

Roger G. Pertwee ◽

...

Keyword(s):

Methyl Ester ◽

Cannabis Sativa ◽

Brain Area ◽

Acid Methyl Ester ◽

Hypothalamic Nucleus ◽

Synthetic Analogue ◽

Neuronal Nuclei ◽

Cannabidiolic Acid ◽

Dorsomedial Hypothalamic Nucleus ◽

Psychotropic Compound

Abstract Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

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The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation

Physiology & Behavior ◽

10.1016/s0031-9384(02)00756-4 ◽

2002 ◽

Vol 76 (3) ◽

pp. 431-442 ◽

Cited By ~ 144

Author(s):

Larry L. Bellinger ◽

Lee L. Bernardis

Keyword(s):

Body Weight ◽

Ingestive Behavior ◽

Hypothalamic Nucleus ◽

Weight Regulation ◽

Body Weight Regulation ◽

Dorsomedial Hypothalamic Nucleus

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The Dorsomedial Hypothalamic Nucleus Is Not Necessary for the Expression of Circadian Food-Anticipatory Activity in Rats

Journal of Biological Rhythms ◽

10.1177/0748730407307804 ◽

2007 ◽

Vol 22 (6) ◽

pp. 467-478 ◽

Cited By ~ 91

Author(s):

Glenn J. Landry ◽

Glenn R. Yamakawa ◽

Ian C. Webb ◽

Rhiannon J. Mear ◽

Ralph E. Mistlberger

Keyword(s):

Hypothalamic Nucleus ◽

Food Anticipatory Activity ◽

Dorsomedial Hypothalamic Nucleus ◽

Anticipatory Activity

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The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity

Nutrition & Metabolism ◽

10.1186/s12986-021-00582-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Yuko Maejima ◽

Shoko Yokota ◽

Masaru Shimizu ◽

Shoichiro Horita ◽

Daisuke Kobayashi ◽

...

Keyword(s):

Nucleus Tractus Solitarius ◽

Physiological Role ◽

Feeding Pattern ◽

Hypothalamic Nucleus ◽

Acid Decarboxylase ◽

Mrna Levels ◽

Dorsomedial Hypothalamic Nucleus ◽

Fos Expression ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Abstract Background Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive. Methods To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured. Results This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS. Conclusion These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.

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