scholarly journals Hypothalamic and Hindbrain Melanocortin Receptors Contribute to the Feeding, Thermogenic, and Cardiovascular Action of Melanocortins

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5351-5361 ◽  
Author(s):  
Karolina P. Skibicka ◽  
Harvey J. Grill
Keyword(s):  
Energy Expenditure ◽  
Nucleus Tractus Solitarius ◽  
Melanocortin Receptor ◽  
Ventrolateral Medulla ◽  
Melanocortin Receptors ◽  
Projection Neurons ◽  
Response Profile ◽  
Feeding Effects ◽  
Retrochiasmatic Area ◽  
Stimulation Of

Abstract Forebrain ventricular delivery of melanocortin receptor (MC3/4R) agonist increases energy expenditure and decreases food intake (FI). Because forebrain ventricular delivery provides ligand to various anatomically distributed MC3/4R-bearing nuclei, it is unclear which of the receptor subpopulations contributes to the feeding suppression and the sympathetic-thermogenic effects observed. The literature indicates that reexpression of MC4R in the paraventricular nucleus (PVH) affects the feeding but not the energetic phenotype of the MC4R knockout, suggesting that divergent MC4R populations mediate energy expenditure (hindbrain) and FI (hypothalamus) effects of stimulation. Not consistent with this view are data indicating that PVH sympathetic projection neurons express MC4Rs and that feeding effects are induced from hindbrain MC4R sites. Therefore, we hypothesize an opposing perspective: that stimulation of anatomically diverse MC3/4R-bearing nuclei triggers energetic as well as feeding effects. To test this hypothesis, ventricle subthreshold doses of MC3/4R agonist (5 and 10 pmol) were applied in separate experiments to six hindbrain and hypothalamic sites; core temperature (Tc), heart rate (HR), spontaneous activity (SPA), and FI were measured in behaving rats. Nucleus tractus solitarius and PVH stimulation increased Tc, HR, and SPA and decreased FI. Rostral ventrolateral medulla, parabrachial nucleus, and retrochiasmatic area stimulation increased Tc, HR, but not SPA, and decreased FI. The response profile differed to some extent for each nucleus tested, suggesting differential output circuitries for the measured parameters. Data are consistent with the view that energetic and feeding responses are not controlled by regionally divergent MC3/4Rs and can be elicited from multiple, anatomically distributed MC3/4R populations.

scholarly journals Rostral ventrolateral medullary but not medullary lateral tegmental field neurons mediate sympatho-sympathetic reflexes in cats

2010 ◽  
Vol 299 (5) ◽  
pp. R1269-R1278 ◽  
Author(s):  
Susan M. Barman ◽  
Hakan S. Orer
Keyword(s):  
Nmda Receptors ◽  
Nucleus Tractus Solitarius ◽  
Excitatory Amino Acid ◽  
Critical Role ◽  
Area Under The Curve ◽  
Splanchnic Nerve ◽  
Ventrolateral Medulla ◽  
Afferent Fibers ◽  
The Right ◽  
Stimulation Of

This study was designed to build on past work from this laboratory by testing the hypothesis that medullary lateral tegmental field (LTF) neurons play a critical role in mediating sympathoexcitatory responses to activation of sympathetic afferent fibers. We studied the effects of microinjection of N-methyl-d-aspartate (NMDA) or non-NMDA receptor antagonists or muscimol bilaterally into the LTF on the area under the curve of the computer-averaged sympathoexcitatory potential in the right inferior cardiac nerve elicited by short trains of stimuli applied to afferent fibers in the left inferior cardiac or left splanchnic nerve (CN, SN) of baroreceptor-denervated and vagotomized cats anesthetized with a mixture of diallylbarbiturate and urethane. In contrast to our hypothesis, sympathoexcitatory responses to stimulation of CN ( n = 5–7) or SN ( n = 4–7) afferent fibers were not significantly affected by these procedures. We then determined whether the rostral and caudal ventrolateral medulla (RVLM, CVLM) and nucleus tractus solitarius (NTS) were involved in mediating these reflexes. Blockade of non-NMDA, but not NMDA, receptors in the RVLM significantly reduced the area under the curve of the sympathoexcitatory responses to electrical stimulation of either CN ( P = 0.0110; n = 6) or SN ( P = 0.0131; n = 5) afferent fibers. Neither blockade of excitatory amino acid receptors nor chemical inactivation of CVLM or NTS significantly affected the responses. These data show that activation of non-NMDA receptors in the RVLM is a critical step in mediating the sympatho-sympathetic reflex.

scholarly journals PD-1+ melanocortin receptor dependent-Treg cells prevent autoimmune disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fauziyya Muhammad ◽  
Dawei Wang ◽  
Alyssa Montieth ◽  
Stacey Lee ◽  
Janine Preble ◽  
...  
Keyword(s):  
Body Mass Index ◽  
T Cells ◽  
Treg Cells ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Healthy Controls ◽  
Lower Body ◽  
Direct Stimulation ◽  
Experimental Autoimmune ◽  
Stimulation Of

AbstractExperimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis marked by ocular autoantigen-specific regulatory immunity in the spleen. The melanocortin 5 receptor (MC5r) and adenosine 2 A receptor (A2Ar) are required for induction of post-EAU regulatory T cells (Tregs) which provide resistance to EAU. We show that blocking the PD-1/PD-L1 pathway prevented suppression of EAU by post-EAU Tregs. A2Ar induction of PD-1+FoxP3+ Tregs in uveitis patients was similar compared to healthy controls, but was significantly reduced with melanocortin stimulation. Further, lower body mass index correlated with responsiveness to stimulation of this pathway. These observations indicate an importance of the PD-1/PD-L1 pathway to provide resistance to relapsing uveitis and shows a reduced capacity of uveitis patients to induce Tregs when stimulated through melanocortin receptors, but that it is possible to bypass this part of the pathway through direct stimulation of A2Ar.

scholarly journals Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

2014 ◽  
Vol 306 (9) ◽  
pp. R681-R692 ◽  
Author(s):  
Priscila S. Guimaraes ◽  
Domitila A. Huber ◽  
Maria J. Campagnole-Santos ◽  
Ann M. Schreihofer
Keyword(s):  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Ventrolateral Medulla ◽  
Zucker Rats ◽  
Adult Rats ◽  
Afferent Nerves ◽  
Afferent Fibers ◽  
Obese Zucker Rats ◽  
Fos Expression ◽  
Stimulation Of

Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with adult lean Zucker rats (LZR) and juvenile OZR (6–7 wk). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared with LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brain stem sites that mediate baroreflexes. In conscious adult rats, a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in the nucleus tractus solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR develop impaired glutamatergic activation of the NTS, which likely contributes to attenuated baroreflexes in adult OZR.

Stimulation of 5-HT2 receptors in the nucleus tractus solitarius enhances NMDA receptor-mediated reflex-evoked bradycardiac responses in the rat

2001 ◽  
Vol 92 (1-2) ◽  
pp. 45-55 ◽  
Author(s):  
Awa N'Diaye ◽  
Caroline Sévoz-Couche ◽  
Anne Nosjean ◽  
Michel Hamon ◽  
Raul Laguzzi
Keyword(s):  
Nmda Receptor ◽  
Nucleus Tractus Solitarius ◽  
Stimulation Of

scholarly journals Multimodal Medullary Neurons and Correlational Linkages of the Respiratory Network

1999 ◽  
Vol 82 (1) ◽  
pp. 188-201 ◽  
Author(s):  
Zhongzeng Li ◽  
Kendall F. Morris ◽  
David M. Baekey ◽  
Roger Shannon ◽  
Bruce G. Lindsey
Keyword(s):  
Firing Rate ◽  
Nucleus Tractus Solitarius ◽  
Motor Pattern ◽  
Sensory Modality ◽  
Spike Trains ◽  
Negative Feedback Regulation ◽  
Firing Rates ◽  
Respiratory Network ◽  
Cross Correlation Analysis ◽  
Stimulation Of

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan–anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and “limit” changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.

Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases

1990 ◽  
Vol 64 (4) ◽  
pp. 1115-1124 ◽  
Author(s):  
A. Randich ◽  
K. Ren ◽  
G. F. Gebhart
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Nucleus Tractus Solitarius ◽  
Cardiovascular Response ◽  
Ibotenic Acid ◽  
Vagal Afferents ◽  
Ventrolateral Medulla ◽  
Tail Flick ◽  
Threshold Intensity ◽  
Arterial Blood

1. Supraspinal substrates mediating vagal afferent stimulation (VAS)-induced inhibition of the nociceptive tail-flick reflex were examined by the use of the soma-selective neurotoxin ibotenic acid and the nonselective local anesthetic lidocaine. Fifty rats were studied in the lightly anesthetized state maintained with pentobarbital sodium. 2. The threshold intensity of VAS required to inhibit the tail-flick reflex to a cut-off latency of 10 s was established in all rats. Ibotenic acid (5 or 10 micrograms, 0.5 microliter) or lidocaine (4%, 0.5 microliter) was then microinjected into various regions of the brain stem followed by reestablishment of the intensity of VAS required to produce inhibition of the tail-flick reflex. 3. Microinjections of ibotenic acid into the ipsilateral nucleus tractus solitarius (NTS), medial rostroventral medulla (principally the nucleus raphe magnus; NRM), or bilaterally into the dorsolateral pons (principally the locus coeruleus/subcoeruleus; LC/SC), significantly increased the threshold intensity of VAS required to inhibit the tail-flick reflex. Microinjections of ibotenic acid into either the rostral or caudal ventrolateral medulla (RVLM or CVLM, respectively) ipsilateral to the vagus nerve stimulated or ipsilateral LC/SC did not significantly affect the inhibition produced by VAS. Arterial blood pressure decreases produced by VAS were significantly attenuated or eliminated after microinjections of ibotenic acid into the NTS, RVLM, CVLM, or NRM. Lidocaine microinjected into the ipsilateral CVLM also significantly increased the intensity of VAS required to inhibit the tail-flick reflex. 4. These outcomes obtained with behavioral measures are consistent with the outcomes of the preceding study using electrophysiological measures in establishing that cells in the NTS, LC/SC, and NRM regions and fibers of passage in the CVLM are important in mediating the inhibitory effects of VAS. The present studies confirm previous reports of the importance of the RVLM and CVLM in VAS-produced depressor responses but also demonstrate that the NRM is critical for this cardiovascular response.

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