Subnuclei Of Paraventricular Nucleus Research Articles

Activated Oxytocin Neurons in the PVN-DVC Pathway in Asthmatic Rats.

Asthma is a heterogeneous disease, and the central nervous system (CNS) also participates in the pathogenesis of asthma. We previously reported the amygdala might regulate asthmatic attacks via projecting to the paraventricular hypothalamic nucleus (PVN). The dorsal vagal complex (DVC) is a crucial region that modulates respiratory. This study aimed to observe the activity in both PVN and DVC and the connection between PVN and DVC in asthmatic rats. Immunohistochemistry was conducted to observe the changes in Fos and oxytocin (OT) expression. Retrograde tracing using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and double immunohistochemistry for OT and Fos was used to observe the HRP/OT/Fos positive neurons distribution in the PVN. The results showed that during an asthma attack, the Fos positive neurons increased in both PVN and DVC over time. The expression of OT positive neurons in PVN showed a similar trend in parallel to the c-Fos positive neurons in PVN. The HRP retrograde-labeled neurons were densely distributed in the medial and lateral subnucleus in the PVN. OT+/HRP+ and Fos+/OT+/HRP+ accounted for 18.14%, and 2.37% of HRP-labeled neurons, respectively. Our study showed PVN and DVC were activated and the expression of OT positive neurons in PVN were increased over time during an asthma attack. The existence of connection between PVN and DVC suggested the OT neurons in PVN might project to DVC which might be involved in the pathogenesis of asthma.

Distribution of D1 and D2 receptor- immunoreactive neurons in the paraventricular nucleus of the hypothalamus in the rat

The paraventricular nucleus (PVN) of the hypothalamus is an important center in regulating the functions of internal organs, and it is the key nucleus for coordinating endocrine, behavior and autonomic stress responses. Dopamine receptors are widely expressed in the hypothalamus and participate in the regulation of many vital activities, such as blood pressure and glycolipid metabolism, but the details of the cellular localization of dopamine receptors in the PVN are not clear. The present study investigated the distribution of D1 and D2 receptor-immunoreactive (IR) neurons in the subnuclei of the PVN and their co-labeling with vasopressin (VP) and oxytocin (OT) in rats by means of Nissl staining and immunofluorescence. The PVN is subdivided into magnocellular and parvicellular subnuclei. The results showed that the D1 receptor-IR neurons were primarily located in the magnocellular subnuclei and distributed throughout several regions of the PVN, including the paraventricular hypothalamic nucleus, lateral magnocellular part (PaLM), medial magnocellular part (PaMM) and posterior part (PaPO). Additionally, the neurons co-labeled with OT and VP. D2 receptor-IR neurons had a distribution pattern similar to that of D1 receptors. The D1- and D2-IR neurons in the subnuclei of the PVN were in relatively close proximity to the fornix. Several subnuclei gradually shifted from the ventral medial aspect of the fornix to the dorsal side when examined along the rostrocaudal axis. In summary, D1 and D2 receptors are widely distributed in the subnuclei of PVN in a similar distribution pattern with a slightly less number of D2 receptor immunoreactive neurons than that of D1. Moreover, D1 and D2 receptors are coexisted with VP and OT. The present study provides important morphological evidence for the function of dopamine receptors in the PVN.

Peripheral chemoreceptors mediate training‐induced plasticity in paraventricular nucleus pre‐autonomic oxytocinergic neurons

We showed previously that sino-aortic denervation prevented training-induced plasticity in pre-autonomic oxytocinergic neurons and blocked the beneficial effects of training. In this study, we investigate the combined effect of training and removal of specific chemoreceptor afferents on both cardiovascular parameters and oxytocin (OT) gene and protein expression within the hypothalamic paraventricular nucleus (PVN). Wistar rats and spontaneously hypertensive rats (SHRs) underwent carotid body denervation or sham surgery and were trained or kept sedentary for 3 months. After haemodynamic measurements at rest, rats were anaesthetized for brain perfusion. Fresh (perfused with PBS) and fixed brains (perfused with 4% paraformaldehyde) were processed for PVN OT mRNA (real-time PCR) and OT immunoreactivity within PVN subnuclei. In sham-operated rats, training improved treadmill performance and reduced resting heart rate (Wistar, -8%; SHRs, -10%), with a reduction in blood pressure only in SHRs (-8%). Training was accompanied by increased PVN OT mRNA expression (twofold increase in sham-operated SHRs) and peptide density in the posterior, ventromedial and dorsal cap PVN subnuclei (on average 70% increase in both strains), with significant correlations between OT content and training-induced resting bradycardia in sham-operated groups. Carotid body denervation did not interfere with the performance gain, abolished chemoreflex activation (without changing baroreflex control) and blocked training-induced cardiovascular adaptations and training-induced changes in PVN OT content in both strains. After carotid body denervation, there was no correlation between OT mRNA or OT immunoractivity and resting heart rate. The chronic absence of chemoreceptor inputs uncovers an unknown role of chemoreceptor signalling in driving the plasticity/activity of PVN oxytocinergic pre-autonomic neurons, thus mediating training-induced cardiovascular adaptive responses.

C‐Fos immunoreactivity (CFI) analysis of sympathetic and non‐sympathetic neural pathways in chronic DOCA‐salt hypertension: effect of benzamil hydrochloride

Intracerebroventricular (ICV) infusion of benzamil attenuates DOCA‐salt hypertension. We examined which brain regions may be involved in this response. Uninephrectomized rats were instrumented with an ICV catheter connected to a minipump delivering either benzamil (16 nmol/day) or vehicle. DOCA (50 mg) or vehicle was implanted subcutaneously, creating four groups: benzamil and DOCA (n=7), benzamil but no DOCA (n=7), DOCA but no benzamil (n=6), or neither benzamil nor DOCA (n=6). Rats drank 0.9% NaCl / 0.2% KCl for 33 days. We analyzed CFI in 5 distinct regions of the hypothalamic paraventricular nucleus (PVN), as well as in supraoptic nucleus (SON), rostroventrolateral medulla (RVLM), and the nucleus of the tractus solitarious (NTS). DOCA increased CFI in all regions of the PVN and in the SON but had no effect in the RVLM or NTS. Benzamil attenuated CFI in two PVN subnuclei: posterior magnocellular neurons and medial parvocellular (mp) neurons, as well as in the SON. These findings support the hypothesis that increasing neural activity plays a role in chronic DOCA‐salt hypertension, and that benzamil attenuates this increase. Benzamil seems to specifically target neurons that play a role in neuroendocrine responses, as it attenuated CFI in the magnocellular vasopressinergic neurons of the PVN and SON, as well as the mp (corticotropin‐releasing hormone positive) neurons of the PVN. (HL064178)

Exercise training-induced remodeling of paraventricular nucleus (nor)adrenergic innervation in normotensive and hypertensive rats

Activation of oxytocin (OT)ergic projections from the hypothalamic paraventricular nucleus (PVN) to the nucleus tractus solitarii contributes to cardiovascular adjustments during exercise training (EXT). Moreover, a deficit in this central OTergic pathway is associated with altered cardiovascular function in hypertension. Since PVN catecholaminergic inputs, known to be activated during EXT, modulate PVN cardiovascular-related functions, we aimed here to determine whether remodeling of PVN (nor)adrenergic innervation occurs during EXT and whether this phenomenon is affected by hypertension. Confocal immunofluorescence microscopy and tract tracing were used to quantify changes in (nor)adrenergic innervation density in PVN subnuclei and in identified dorsal vagal complex (DVC) projecting neurons (PVN-DVC) in EXT normotensive [Wistar-Kyoto rat (WKY)] and hypertensive [spontaneously hypertensive rat (SHR)] rats. In WKY, EXT increased the density of PVN dopamine beta-hydroxylase immunoreactivity (DBHir) (160%). Furthermore, the number and density of DBHir boutons overlapping PVN-DVC OTergic neurons were also increased during EXT (130%), effects that were blunted in SHR. Conversely, while DBHir in the medial parvocellular subnucleus (an area enriched in corticotropin-releasing hormone neurons) was not changed by EXT in WKY, a diminished DBHir was observed in trained SHR. Overall, these data support the concept that the PVN (nor)adrenergic innervation undergoes plastic remodeling during EXT, an effect that is differentially affected during hypertension. The functional implications of PVN (nor)adrenergic remodeling in relation to the central peptidergic control of cardiovascular function during EXT are discussed.

Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat

The lateral preoptic and lateral hypothalamic regions contain the majority of the cell groups embedded in the fibre trajectories of the medial forebrain bundle on its course through the hypothalamus. Recent studies have extended considerably the parcellation of the lateral hypothalamic region, and therefore, the need to emphasize new insights into the anatomical organisation of projections from the neurons of the lateral hypothalamic region. In the present study we describe the anatomical organisation of efferent projections from the lateral preoptic and lateral hypothalamic regions to the hypothalamic paraventricular nucleus (PVN) on the basis of retrograde- and anterograde-tracing techniques. Iontophoretic injections of the retrograde tracer, cholera toxin subunit B, into the PVN revealed that most hypothalamic nuclei project to the PVN. Within the lateral hypothalamic region, retrogradely labelled cells were concentrated in the intermediate hypothalamic area, the lateral hypothalamic area, and the perifornical nucleus, whereas fewer retrogradely labelled cells were found in the lateral preoptic area. To determine the distribution of terminating fibres in subnuclei of the heterogeneous PVN, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were delivered into distinct areas of the lateral hypothalamic region. Neurons of the intermediate hypothalamic area projected mainly to the PVN subnuclei, which contained parvicellular neuroendocrine cells. In contrast, neurons of the rostral and tuberal parts of the lateral hypothalamic area and the perifornical nucleus projected to the PVN subnuclei, which contained parvicellular neurons that send descending projections to preganglionic cell groups in the medulla and spinal cord. The perifornical nucleus was the only area within the lateral hypothalamic region that consistently innervated magnocellular perikarya of the PVN. Finally, all areas of the lateral hypothalamic region contributed substantially to fibres terminating in the perinuclear shell of the PVN. These results demonstrate that anatomically distinct areas of the lateral hypothalamic region have distinct projections to subnuclei of the PVN and further substantiate the view that the lateral hypothalamic region as well as the PVN constitute anatomically and functionally heterogeneous structures.

Neurons in the paraventricular nucleus of the hypothalamus that project to the sexually dimorphic lower lumbar spinal cord concentrate 3H-estradiol in the male rat.

The location and distribution of estradiol-concentrating neurons in the hypothalamus afferent to segments of lumbar spinal cord that contain the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) were determined by combining retrograde fluorescent tract tracing with steroid hormone autoradiography. Injections of Fluorogold were made into segments of L5-L6 of the spinal cord of adult male rats and 12 days later animals were castrated. One week following castration, males received injections of [3H]estradiol and were perfused. Their brains were then processed for steroid hormone autoradiography. Following exposure times of 11 to 12 months, autoradiograms were developed and the hypothalamus was analyzed for neurons that concentrate estradiol and project to the spinal cord. Numerous neurons in the hypothalamus projected to the spinal cord, specifically neurons in the paraventricular nucleus (PVN), the lateral hypothalamus and the dorsal area of the hypothalamus. Although many subnuclei of PVN, as well as lateral hypothalamus, contained Fluorogold labelled neurons and estradiol concentrating neurons, the majority of double labeled cells were found in the lateral parvocellular (LP) subnucleus of PVN. Approximately 30% of the neurons in the lp subnucleus that projected to spinal cord also concentrated estradiol. Up to one half of the estradiol-concentrating neurons in lp sent axons to the lower lumbar spinal cord. These results suggest that some of the effects of gonadal steroid hormones on SNB development, plasticity and function may in fact, be indirect, via steroid-sensitive afferents.