The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus

Affleck, VS; Coote, John H.; Pyner, Susan

doi:10.1016/j.neuroscience.2012.05.070

Cited by 92 publications

(72 citation statements)

References 67 publications

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“…We presented not only light microscopic, but also fine structural details and synaptology of nNOS-immunopositive septal neuronal elements. Fine structural immunocytochemical studies are rather rare in this field and they deal with other parts of the CNS, such as the spinal cord [43], nucleus of the solitary tract [5], periaqueductal grey matter [7], hypothalamus [1] or visual cortex [29]. Independently of the examined brain area the fine structural characteristics of the nNOS-immunopositive neurons, terminals and dendrites are astonishingly similar to each other as well as to our findings.…”

Section: Discussionsupporting

confidence: 87%

Fine structure and synaptology of the nitrergic neurons in medial septum of the rat brain

Halasy¹,

Szőke²,

Janzsó³

2017

Acta Biologica Hungarica

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The nitrergic neuron population and certain aspects of their connectivity (peptidergic inputs, co-localization with GABA, synaptic target distribution) were studied in the medial septum of the rat brain. The histochemical localization of NADPH diaphorase and immunohistochemical identification of nNOS at light and electron microscopic level was applied. Double-labeling experiments with galanin and leucine enkephalin, moreover the postembedding GABA immunogold staining was also carried out. NADPH diaphorase-and nNOS-immunopositive neurons could be identified inside the borders of medial septum. Out of their peptidergic inputs galanin-and leucine enkephaline-immunopositive varicose fibers were found in close apposition with nNOS-immunopositive neurons. Based on fine structural characteristics (large indented nucleus, thin cytoplasmic rim, lack of axosomatic synapses) the nitrergic neurons are suggested to be identical with the septal cholinergic nerve cells. Their boutons established asymmetrical synapses mainly on dendritic shafts and spines, some of which were also nNOS-immunopositive. A lower amount of nNOS-immunopositive boutons of presumably extrinsic origin were found to be GABAergic.

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Section: Discussionsupporting

confidence: 87%

Fine structure and synaptology of the nitrergic neurons in medial septum of the rat brain

Halasy¹,

Szőke²,

Janzsó³

2017

Acta Biologica Hungarica

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“…The functional consequences of these distinct stage-dependent responses need to be interpreted through the location and role of these brain-stem nuclei in the blood pressure control circuit. The NTS is known to be the primary site of cardiorespiratory regulatory integration (1,8,9,13,33,46,47). The RVLM receives inhibitory projections from the caudal ventrolateral medulla.…”

Section: Discussionmentioning

confidence: 99%

“…The primers are listed in Supplemental Table S6. 1 Gene expression data analysis. Targets assayed were chosen based on their role in neuromodulation, inflammation, and catecholaminergic regulation from literature and previous unpublished data from this lab.…”

Section: Methodsmentioning

confidence: 99%

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MicroRNA network changes in the brain stem underlie the development of hypertension

DeCicco

Zhu

Brureau

et al. 2015

Physiological Genomics

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sion is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 wellannotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage-and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.hypertension; microRNA; neuroinflammation; angiotensin II; brain stem HYPERTENSION IS A MAJOR CHRONIC disease worldwide, affecting about 50 million adults in the United States alone. It is a multiorgan disease and a major cause of heart failure, coronary heart disease, atrial fibrillation, stroke, and end-stage renal disease, and it has an enormous economic impact. About 90 -95% of cases are "essential" with no known medical cause (11). Moreover, only about a third of hypertensive patients have their blood pressure fully controlled (11). A significant and increasing population (ϳ25%) of hypertensive patients is drug resistant. There remains an unmet need for antihypertensive therapy.In the context of the recent discovery of novel lines of therapeutic interventions involving approaches to modulate microRNA we decided to elucidate changes in microRNA levels during the development of spontaneous hypertensive rat (SHR) hypertension. The recent explosion in microRNA research has produced new computational and experimental approaches for studying microRNA functions in cell culture and in vivo, which we take advantage of here. MicroRNAs are an abundant class of small (ϳ22 nt) endogenous noncoding RNAs that direct posttranscriptional regulation of gene expression. There is ample evidence that dysregulation of microRNAs is associated with the pathogenesis of human diseases, in...

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“…PVN presympathetic neurons receive afferent projections from the NTS. 32 NTS neurons innervate GABAergic neurons in the caudal ventrolateral medulla, which, in turn, innervate neurons in the RVLM. 33 It was reported that intracerebroventricular injection of IMD caused a pressor effect and sympathetic activation.…”

Section: Discussionmentioning

confidence: 99%

Intermedin in Paraventricular Nucleus Attenuates Sympathetic Activity and Blood Pressure via Nitric Oxide in Hypertensive Rats

et al. 2014

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I ntermedin (IMD) or adrenomedullin (AM) 2 is a member of the calcitonin/calcitonin gene-related peptide (CGRP) family discovered in 2004.1 Unlike other members of this family, no unique receptor has yet been identified for IMD. IMD, CGRP, and AM share the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activitymodifying proteins (RAMPs). The CRLR/RAMP1 forms the CGRP receptor, whereas CRLR/RAMP2 or CRLR/RAMP3 complex forms the AM receptor. IMD binds nonselectively to all 3 CRLR/RAMP complexes.2 IMD is widely distributed in peripheral organs and the central nervous system. 3,4 CRLR and RAMPs have been found in the paraventricular nucleus (PVN) of hypothalamus, 2,5,6 and abundant IMD-like immunoreactivity have been found in the PVN including parvocellular and magnocellular cells. 4,7 PVN is an important integrative site implicated in the neurogenic component of 2-kidney 1-clip (2K1C)-induced renovascular hypertension 8 and contributes to sympathetic activation and hypertension in 2K1C rats. 9 Intracerebroventricular injection of IMD increased mean arterial pressure (MAP) and sympathetic activity. 10 A recent study in our laboratory has shown that microinjection of IMD into the nucleus tractus solitarii (NTS) increased renal sympathetic nerve activity (RSNA) and MAP. 11 It is interesting to know the roles and mechanisms of IMD in the PVN in sympathetic activation and hypertension because of the importance of the PVN in the pathogenesis of hypertension in 2K1C rats.Inhibition of nitric oxide (NO) synthase (NOS) in the PVN increased MAP and heart rate (HR), whereas NO donor sodium nitroprusside produced depressor responses in normal rats.12 Downregulation of NO was involved in renal wrapAbstract-Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hypertension. Rats were subjected to 2-kidney 1-clip (2K1C) surgery to induce renovascular hypertension or sham operation. Acute experiments were performed 4 weeks later under anesthesia. IMD mRNA and protein were downregulated in 2K1C rats. Bilateral PVN microinjection of IMD caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in 2K1C rats than in sham-operated rats, which were prevented by pretreatment with adrenomedullin receptor antagonist AM22-52 or nonselective nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, and attenuated by selective neuronal NO synthase inhibitor N ω -propyl-l-arginine hydrochloride or endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-l-ornithine dihydrochloride. AM22-52 increased renal sympathetic nerve activity and mean arterial pressure in 2K1C rats but not in sham-operated rats, whereas calcitonin/calciton...

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The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus

Abstract: Highlights► Ascending NTS fibres target PVN-associated neurons. ► Suggest glutamate as the neurotransmitter. ► Anatomical basis for the different functions of cardiovascular receptors.

Cited by 92 publications

References 67 publications

Fine structure and synaptology of the nitrergic neurons in medial septum of the rat brain

Fine structure and synaptology of the nitrergic neurons in medial septum of the rat brain

MicroRNA network changes in the brain stem underlie the development of hypertension

Intermedin in Paraventricular Nucleus Attenuates Sympathetic Activity and Blood Pressure via Nitric Oxide in Hypertensive Rats

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