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Ronald M Lechan - One of the best experts on this subject based on the ideXlab platform.
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neuroanatomical evidence for participation of the hypothalamic Dorsomedial Nucleus dmn in regulation of the hypothalamic paraventricular Nucleus pvn by α melanocyte stimulating hormone
Brain Research, 2005Co-Authors: Praful S Singru, Csaba Fekete, Ronald M LechanAbstract:Abstract To test the hypothesis that neurons in the hypothalamic paraventricular Nucleus (PVN) may be under both direct and indirect regulation by alpha melanocyte-stimulating hormone (α-MSH)-synthesizing neurons of the arcuate Nucleus, we determined whether the retrogradely transported marker substance, cholera toxin β-subunit (CtB), when injected into the PVN, labels distinct populations of neurons in the hypothalamic Dorsomedial Nucleus (DMN) that are innervated by axon terminals containing α-MSH. Following iontophoresis of CtB into the PVN, retrogradely labeled neurons were identified in the DMN primarily on the same side as the injection, although a few neurons were also identified in the opposite side of the DMN. The greatest percentage of retrogradely labeled DMN neurons were located in the medial portion of the ventral subdivision of the DMN (DMNv), accounting for approximately 64.8 ± 1.1% of all CtB-labeled cells in the DMN. The second largest population, comprising 25.9 ± 1.6% of the total number of CtB cells in the DMN, was diffusely distributed in the dorsal subdivision of the DMN (DMNd). Only 9.4 ± 0.3% of the CtB-labeled cells were located in the compact zone of the DMN (DMNc). In double-labeling immunofluorescent preparations, 61.1 ± 1.0% of the CtB cells in the DMNv, 38.6 ± 0.9% of the CtB cells in the DMNd, and 13.1 ± 1.3% of the CtB cells in the DMNc were contacted by axon terminals containing α-MSH. These data establish that neurons in discrete regions in the DMN may be influenced by the melanocortin signaling system and thereby, could serve as important relay sites to the PVN.
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hypothalamic Dorsomedial Nucleus neurons innervate thyrotropin releasing hormone synthesizing neurons in the paraventricular Nucleus
Brain Research, 2001Co-Authors: Emese Mihaly, Csaba Fekete, Ronald M Lechan, Gabor LegradiAbstract:Abstract To determine whether the hypothalamic Dorsomedial Nucleus (DMN) may serve as a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular Nucleus (PVN), axonal projections from the DMN to TRH-containing neurons in the PVN were studied using the anterogradely transported marker substance, Phaseolus vulgaris-leucoagglutinin (PHA-L). Stereotaxic injections of PHA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10–14-day survival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the DMN were identified in 14 animals and gave rise to a fiber bundle that entered the PVN at the caudal pole of the Nucleus, densely innervating all parvocellular subdivisions of the PVN. In double-labeled preparations using antisera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-containing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the entire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon varicosities were juxtaposed to ∼97 and 90% of proTRH neurons, respectively, in all parvocellular subdivisions of the PVN, and by ultrastructural analysis were shown to be synaptic. In contrast, when the injection site was centered primarily in the mid-ventral part of the DMN, only ∼52% of proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synthesizing neurons in the PVN.
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hypothalamic Dorsomedial Nucleus neurons innervate thyrotropin releasing hormone synthesizing neurons in the paraventricular Nucleus
Brain Research, 2001Co-Authors: Emese Mihaly, Csaba Fekete, Ronald M Lechan, Gabor LegradiAbstract:To determine whether the hypothalamic Dorsomedial Nucleus (DMN) may serve as a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular Nucleus (PVN), axonal projections from the DMN to TRH-containing neurons in the PVN were studied using the anterogradely transported marker substance, Phaseolus vulgaris-leucoagglutinin (PHA-L). Stereotaxic injections of PHA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10-14-day survival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the DMN were identified in 14 animals and gave rise to a fiber bundle that entered the PVN at the caudal pole of the Nucleus, densely innervating all parvocellular subdivisions of the PVN. In double-labeled preparations using antisera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-containing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the entire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon varicosities were juxtaposed to approximately 97 and 90% of proTRH neurons, respectively, in all parvocellular subdivisions of the PVN, and by ultrastructural analysis were shown to be synaptic. In contrast, when the injection site was centered primarily in the mid-ventral part of the DMN, only approximately 52% of proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synthesizing neurons in the PVN.
Csaba Fekete - One of the best experts on this subject based on the ideXlab platform.
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neuroanatomical evidence for participation of the hypothalamic Dorsomedial Nucleus dmn in regulation of the hypothalamic paraventricular Nucleus pvn by α melanocyte stimulating hormone
Brain Research, 2005Co-Authors: Praful S Singru, Csaba Fekete, Ronald M LechanAbstract:Abstract To test the hypothesis that neurons in the hypothalamic paraventricular Nucleus (PVN) may be under both direct and indirect regulation by alpha melanocyte-stimulating hormone (α-MSH)-synthesizing neurons of the arcuate Nucleus, we determined whether the retrogradely transported marker substance, cholera toxin β-subunit (CtB), when injected into the PVN, labels distinct populations of neurons in the hypothalamic Dorsomedial Nucleus (DMN) that are innervated by axon terminals containing α-MSH. Following iontophoresis of CtB into the PVN, retrogradely labeled neurons were identified in the DMN primarily on the same side as the injection, although a few neurons were also identified in the opposite side of the DMN. The greatest percentage of retrogradely labeled DMN neurons were located in the medial portion of the ventral subdivision of the DMN (DMNv), accounting for approximately 64.8 ± 1.1% of all CtB-labeled cells in the DMN. The second largest population, comprising 25.9 ± 1.6% of the total number of CtB cells in the DMN, was diffusely distributed in the dorsal subdivision of the DMN (DMNd). Only 9.4 ± 0.3% of the CtB-labeled cells were located in the compact zone of the DMN (DMNc). In double-labeling immunofluorescent preparations, 61.1 ± 1.0% of the CtB cells in the DMNv, 38.6 ± 0.9% of the CtB cells in the DMNd, and 13.1 ± 1.3% of the CtB cells in the DMNc were contacted by axon terminals containing α-MSH. These data establish that neurons in discrete regions in the DMN may be influenced by the melanocortin signaling system and thereby, could serve as important relay sites to the PVN.
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hypothalamic Dorsomedial Nucleus neurons innervate thyrotropin releasing hormone synthesizing neurons in the paraventricular Nucleus
Brain Research, 2001Co-Authors: Emese Mihaly, Csaba Fekete, Ronald M Lechan, Gabor LegradiAbstract:Abstract To determine whether the hypothalamic Dorsomedial Nucleus (DMN) may serve as a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular Nucleus (PVN), axonal projections from the DMN to TRH-containing neurons in the PVN were studied using the anterogradely transported marker substance, Phaseolus vulgaris-leucoagglutinin (PHA-L). Stereotaxic injections of PHA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10–14-day survival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the DMN were identified in 14 animals and gave rise to a fiber bundle that entered the PVN at the caudal pole of the Nucleus, densely innervating all parvocellular subdivisions of the PVN. In double-labeled preparations using antisera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-containing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the entire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon varicosities were juxtaposed to ∼97 and 90% of proTRH neurons, respectively, in all parvocellular subdivisions of the PVN, and by ultrastructural analysis were shown to be synaptic. In contrast, when the injection site was centered primarily in the mid-ventral part of the DMN, only ∼52% of proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synthesizing neurons in the PVN.
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hypothalamic Dorsomedial Nucleus neurons innervate thyrotropin releasing hormone synthesizing neurons in the paraventricular Nucleus
Brain Research, 2001Co-Authors: Emese Mihaly, Csaba Fekete, Ronald M Lechan, Gabor LegradiAbstract:To determine whether the hypothalamic Dorsomedial Nucleus (DMN) may serve as a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular Nucleus (PVN), axonal projections from the DMN to TRH-containing neurons in the PVN were studied using the anterogradely transported marker substance, Phaseolus vulgaris-leucoagglutinin (PHA-L). Stereotaxic injections of PHA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10-14-day survival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the DMN were identified in 14 animals and gave rise to a fiber bundle that entered the PVN at the caudal pole of the Nucleus, densely innervating all parvocellular subdivisions of the PVN. In double-labeled preparations using antisera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-containing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the entire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon varicosities were juxtaposed to approximately 97 and 90% of proTRH neurons, respectively, in all parvocellular subdivisions of the PVN, and by ultrastructural analysis were shown to be synaptic. In contrast, when the injection site was centered primarily in the mid-ventral part of the DMN, only approximately 52% of proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synthesizing neurons in the PVN.
L W Swanson - One of the best experts on this subject based on the ideXlab platform.
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projections from bed nuclei of the stria terminalis Dorsomedial Nucleus implications for cerebral hemisphere integration of neuroendocrine autonomic and drinking responses
The Journal of Comparative Neurology, 2006Co-Authors: Hongwei Dong, L W SwansonAbstract:The overall projection pattern of a tiny bed nuclei of the stria terminalis anteromedial group differentiation, the Dorsomedial Nucleus (BSTdm), was analyzed with the Phaseolus vulgaris-leucoagglutinin anterograde pathway tracing method in rats. Many brain regions receive a relatively moderate to strong input from the BSTdm. They fall into eight general categories: humeral sensory-related (subfornical organ and median preoptic Nucleus, involved in initiating drinking behavior and salt appetite), neuroendocrine system (magnocellular: oxytocin, vasopressin; parvicellular: gonadotropin-releasing hormone, somatostatin, thyrotropin-releasing hormone, corticotropin-releasing hormone), central autonomic control network (central amygdalar Nucleus, BST anterolateral group, descending paraventricular hypothalamic Nucleus, retrochiasmatic area, ventrolateral periaqueductal gray, Barrington's Nucleus), hypothalamic visceromotor pattern-generator network (five of six known components), behavior control column (ingestive: descending paraventricular Nucleus; reproductive: lateral medial preoptic Nucleus; defensive: anterior hypothalamic Nucleus; foraging: ventral tegmental area, along with interconnected Nucleus accumbens and substantia innominata), orofacial motor control (retrorubral area), thalamocortical feedback loops (paraventricular, central medial, intermediodorsal, and medial mediodorsal nuclei; Nucleus reuniens), and behavioral state control (subparaventricular zone, ventrolateral preoptic Nucleus, tuberomammillary Nucleus, supramammillary Nucleus, lateral habenula, and raphe nuclei). This pattern of axonal projections, and what little is known of its inputs suggest that the BSTdm is part of a striatopallidal differentiation involved in coordinating the homeostatic and behavioral responses associated thirst and salt appetite, although clearly it may relate them to other functions as well. The BSTdm generates the densest known inputs directly to the neuroendocrine system from any part of the cerebral hemispheres. J. Comp. Neurol. 494:75–107, 2006. © 2005 Wiley-Liss, Inc.
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structural characterization of a hypothalamic visceromotor pattern generator network
Brain Research Reviews, 2003Co-Authors: Richard H Thompson, L W SwansonAbstract:Abstract A high resolution PHAL analysis of axonal connections suggests the existence of a visceromotor pattern generator network in the periventricular region of the rat hypothalamus (HVPG), and a preliminary account of its structure is provided here. Six nodes identified thus far include the Dorsomedial Nucleus and five small nuclei in the preoptic region (anteroventral and anterodorsal preoptic, parastrial, median preoptic, and anteroventral periventricular). Aside from its location between the neuroendocrine motor zone and the medial hypothalamic nuclei (behavior control column), three other primary features characterize the HVPG network. First, each HVPG Nucleus generates a pattern of terminal fields that differentially targets a unique set of hypothalamic neuroendocrine motoneuron pools, and of preautonomic parts of the paraventricular Nucleus. Second, the six HVPG nuclei are massively interconnected themselves. And third, the majority of projections from the HVPG nuclei remain within the medial half of the hypothalamus; additional outputs reach the septum, other parts of the diencephalon, and the brainstem central gray. Possible control of activity in the HVPG by neural inputs from the cerebral hemispheres, sensory systems, behavioral state-related cell groups, and the hypothalamic behavior or motivation control column is discussed, along with certain key functional data related to HVPG nuclei. Finally, the HVPG is incorporated into a working model of hypothalamic organization.
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basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain
The Journal of Comparative Neurology, 2001Co-Authors: Hongwei Dong, Gorica D Petrovich, Alan G Watts, L W SwansonAbstract:The organization of axonal projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis (BST) was characterized with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracing method in adult male rats. Within the BST, the oval Nucleus (BSTov) projects very densely to the fusiform Nucleus (BSTfu) and also innervates the caudal anterolateral area, anterodorsal area, rhomboid Nucleus, and subcommissural zone. Outside the BST, its heaviest inputs are to the caudal substantia innominata and adjacent central amygdalar Nucleus, retrorubral area, and lateral parabrachial Nucleus. It generates moderate inputs to the caudal Nucleus accumbens, parasubthalamic Nucleus, and medial and ventrolateral divisions of the periaqueductal gray, and it sends a light input to the anterior parvicellular part of the hypothalamic paraventricular Nucleus and Nucleus of the solitary tract. The BSTfu displays a much more complex projection pattern. Within the BST, it densely innervates the anterodorsal area, Dorsomedial Nucleus, and caudal anterolateral area, and it moderately innervates the BSTov, subcommissural zone, and rhomboid Nucleus. Outside the BST, the BSTfu provides dense inputs to the Nucleus accumbens, caudal substantia innominata and central amygdalar Nucleus, thalamic paraventricular Nucleus, hypothalamic paraventricular and periventricular nuclei, hypothalamic Dorsomedial Nucleus, perifornical lateral hypothalamic area, and lateral tegmental Nucleus. Moderately dense inputs are found in the parastrial, tuberal, dorsal raphe, and parabrachial nuclei and in the retrorubral area, ventrolateral division of the periaqueductal gray, and pontine central gray. Light projections end in the olfactory tubercle, lateral septal Nucleus, posterior basolateral amygdalar Nucleus, supramammillary Nucleus, and Nucleus of the solitary tract. These and other results suggest that the BSTov and BSTfu are basal telencephalic parts of a circuit that coordinates autonomic, neuroendocrine, and ingestive behavioral responses during stress.
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organization of inputs to the Dorsomedial Nucleus of the hypothalamus a reexamination with fluorogold and phal in the rat
Brain Research Reviews, 1998Co-Authors: Richard H Thompson, L W SwansonAbstract:Possible inputs to the DMH were studied first using the fluorescent retrograde tracer Fluorogold, and identified cell groups were then injected with the anterograde tracer PHAL to examine the distribution of labeled axons in and around the DMH. From this work, we conclude that the majority of inputs to the DMH arise in the hypothalamus, although there are a few significant projections from the telencephalon and brainstem. With few exceptions, each major Nucleus and area of the hypothalamus provides inputs to the DMH. Telencephalic inputs arise mainly in the ventral subiculum, infralimbic area of the prefrontal cortex, lateral septal Nucleus, and bed nuclei of the stria terminalis. The majority of brainstem inputs arise in the periaqueductal gray, parabrachial Nucleus, and ventrolateral medulla. In addition, it now seems clear that inputs to the DMH use only a few discrete pathways. Descending inputs course through a periventricular pathway through the hypothalamic periventricular zone, a medial pathway that follows the medial corticohypothalamic tract, and a lateral pathway traveling through medial parts of the medial forebrain bundle. Ascending inputs arrive through a midbrain periventricular pathway that travels adjacent to the cerebral aqueduct in the periaqueductal gray, and through a brainstem lateral pathway that travels through central and ventral midbrain tegmental fields and enters the hypothalamus, and then the DMH from more lateral parts of the medial forebrain bundle. The results are discussed in relation to evidence for involvement of the DMH in ingestive behavior, and diurnal and stress-induced corticosterone secretion.
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organization of projections from the Dorsomedial Nucleus of the hypothalamus a pha l study in the rat
The Journal of Comparative Neurology, 1996Co-Authors: Richard H Thompson, Newton S. Canteras, L W SwansonAbstract:The axonal projections of the Dorsomedial Nucleus of the hypothalamus were investigated by using Phaseolous vulgaris-leucoagglutinin. The main conclusion of this work is that these projections are largely intrahypothalamic, with smaller components directed toward the brainstem and telencephalon. Although the intrahypothalamic pathways are very complex and intermix at various levels, we conclude that Dorsomedial Nucleus outputs follow three distinct ascending pathways: periventricular, coursing through the hypothalamic periventricular zone; ventral, traveling beneath the medial zone; and lateral, ascending in medial parts of the lateral hypothalamic area. Within the hypothalamus, the most densely innervated areas are the paraventricular Nucleus, other dorsal regions of the periventricular zone, the preoptic suprachiasmatic Nucleus, and the parastrial Nucleus. Other significant terminal fields include the median preoptic, anteroventral periventricular, lateral part of the medial preoptic, and anteroventral preoptic nuclei; and the retrochiasmatic (including perisuprachiasmatic) area. Descending projections follow two pathways that also converge at various levels: a dorsal pathway in the midbrain periventricular system travels through, and primarily innervates, the periaqueductal and pontine gray, and a ventral pathway extends through ventromedial regions of the brainstem. Although sparse, fibers in the later pathway can be traced as far caudally as the Nucleus of the solitary tract. The results are discussed relative to the pathways and properties of nearby hypothalamic medial zone nuclei. Dorsomedial Nucleus projections are similar to certain other nuclei (e.g., anteroventral periventricular and parastrial) with predominantly intrahypothalamic projections, and different from those arising in the medial zone nuclei (medial preoptic, anterior hypothalamic, ventromedial, and mammillary.
Emese Mihaly - One of the best experts on this subject based on the ideXlab platform.
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hypothalamic Dorsomedial Nucleus neurons innervate thyrotropin releasing hormone synthesizing neurons in the paraventricular Nucleus
Brain Research, 2001Co-Authors: Emese Mihaly, Csaba Fekete, Ronald M Lechan, Gabor LegradiAbstract:Abstract To determine whether the hypothalamic Dorsomedial Nucleus (DMN) may serve as a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular Nucleus (PVN), axonal projections from the DMN to TRH-containing neurons in the PVN were studied using the anterogradely transported marker substance, Phaseolus vulgaris-leucoagglutinin (PHA-L). Stereotaxic injections of PHA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10–14-day survival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the DMN were identified in 14 animals and gave rise to a fiber bundle that entered the PVN at the caudal pole of the Nucleus, densely innervating all parvocellular subdivisions of the PVN. In double-labeled preparations using antisera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-containing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the entire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon varicosities were juxtaposed to ∼97 and 90% of proTRH neurons, respectively, in all parvocellular subdivisions of the PVN, and by ultrastructural analysis were shown to be synaptic. In contrast, when the injection site was centered primarily in the mid-ventral part of the DMN, only ∼52% of proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synthesizing neurons in the PVN.
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hypothalamic Dorsomedial Nucleus neurons innervate thyrotropin releasing hormone synthesizing neurons in the paraventricular Nucleus
Brain Research, 2001Co-Authors: Emese Mihaly, Csaba Fekete, Ronald M Lechan, Gabor LegradiAbstract:To determine whether the hypothalamic Dorsomedial Nucleus (DMN) may serve as a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular Nucleus (PVN), axonal projections from the DMN to TRH-containing neurons in the PVN were studied using the anterogradely transported marker substance, Phaseolus vulgaris-leucoagglutinin (PHA-L). Stereotaxic injections of PHA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10-14-day survival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the DMN were identified in 14 animals and gave rise to a fiber bundle that entered the PVN at the caudal pole of the Nucleus, densely innervating all parvocellular subdivisions of the PVN. In double-labeled preparations using antisera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-containing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the entire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon varicosities were juxtaposed to approximately 97 and 90% of proTRH neurons, respectively, in all parvocellular subdivisions of the PVN, and by ultrastructural analysis were shown to be synaptic. In contrast, when the injection site was centered primarily in the mid-ventral part of the DMN, only approximately 52% of proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synthesizing neurons in the PVN.
Caroline Sevozcouche - One of the best experts on this subject based on the ideXlab platform.
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vulnerability to stress consequences induced by repeated social defeat in rats contribution of the angiotensin ii type 1 receptor in cardiovascular alterations associated to low brain derived neurotrophic factor
European Journal of Pharmacology, 2019Co-Authors: Charly Brouillard, Pascal Carrive, Francoise Camus, J J Benoliel, Caroline SevozcoucheAbstract:Abstract After social stress, rats become vulnerable to depression, and this state is characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF). The aim of this study was to determine whether low BDNF levels are associated with long term autonomic changes. Defeated animals were subjected to four daily episodes of social defeats. Twenty five days later, defeated rats with low BDNF levels (Dlow) still displayed elevated sympathetic tone (as indicated by an elevated low frequency to high frequency ratio (LF/HF) in heart rate) and elevated blood pressure, as well as reduced baroreflex sensitivity (BRS). In contrast, those with higher BDNF levels (Dhigh) similar to controls, did not. Dlow animals persistent cardiovascular changes were abolished by acute inhibition of the Dorsomedial Nucleus of the hypothalamus (DMH). These cardiovascular changes were also prevented by chronic sub-cutaneous osmotic infusion of losartan, an angiotensin II type 1 receptor (AT1) receptor antagonist, started immediately after social defeat. In conclusion, the results show that greater vulnerability to stress consequences following a traumatic event is associated with an elevated LF/HF ratio, a persistent high blood pressure and a low BRS, all due to an AT1 receptor activation.