Magnocellular PVN Research Articles

Effects of chronic silencing of relaxin-3 production in nucleus incertus neurons on food intake, body weight, anxiety-like behaviour and limbic brain activity in female rats.

Eating disorders are frequently triggered by stress and are more prevalent in women than men. First signs often appear during early adolescence, but the biological basis for the sex-specific differences is unknown. Central administration of native relaxin-3 (RLN3) peptide or chimeric/truncated analogues produces differential effects on food intake and HPA axis activity in adult male and female rats, but the precise role of endogenous RLN3 signalling in metabolic and neuroendocrine control is unclear. Therefore, we examined the effects of microRNA-induced depletion (knock-down) of RLN3 mRNA/(peptide) production in neurons of the brainstem nucleus incertus (NI) in female rats on a range of physiological, behavioural and neurochemical indices, including food intake, body weight, anxiety, plasma corticosterone, mRNA levels of key neuropeptides in the paraventricular nucleus of hypothalamus (PVN) and limbic neural activity patterns (reflected by c-fos mRNA). Validated depletion of RLN3 in NI neurons of female rats (n = 8) produced a small, sustained (~ 2%) decrease in body weight, an imbalance in food intake and an increase in anxiety-like behaviour in the large open field, but not in the elevated plus-maze or light/dark box. Furthermore, NI RLN3 depletion disrupted corticosterone regulation, increased oxytocin and arginine-vasopressin, but not corticotropin-releasing factor, mRNA, in PVN, and decreased basal levels of c-fos mRNA in parvocellular and magnocellular PVN, bed nucleus of stria terminalis and the lateral hypothalamic area, brain regions involved in stress and feeding. These findings support a role for NI RLN3 neurons in fine-tuning stress and neuroendocrine responses and food intake regulation in female rats.

C‐Fos Responses Produced by the Central Microinjection of Salvinorin A in Conscious Rats

Intracerebroventricular (ICV) injection of the kappa opioid agonists produces a marked diuresis in rats via inhibition of vasopressin secretion. Salvinorin A (SalA) is a plant‐derived high affinity agonist for the kappa opioid receptor (KOR). Previous studies have proposed that SalA has similar potency and efficacy as other synthetic kappa agonists in mediating the CNS effects of KOR activation. The present study examines the expression of the proto‐oncogene c‐fos in several forebrain regions of rats treated with SalA as compared to either acetonitrile or saline vehicle treated animals. SalA is a highly lipophilic drug and past studies utilized drug dissolving vehicles (e.g., DMSO) that produced significant cardiovascular and renal effects. In this study, we dissolved SalA in acetonitrile/saline (1:9 dilution) to minimize solvent viscosity and cardiovascular effects.MethodsAnimals were habituated to a metabolic cage and injected with either SalA, acetonitrile or saline. Urine samples were collected during two 15 min control periods and six 15 min periods beginning 15 min after injection into the lateral ventricle. After 90 minutes, animals were perfused with a phosphate buffer and PFA. Brains were removed and cut on a cryostat (40 μm thick). Brain sections were processed for c‐fos using a commercially available antibody. Sections were also double labeled with oxytocin to define anatomically specific forebrain regions.ResultsSalA decreased c‐fos expression in the parvocellular PVN, magnocellular PVN, supraoptic (SON) and median pre‐optic (MnPO) nucleus relative to the acetonitrile group. However, only in the parvocellular PVN was the decrease in c‐fos expression statistically significant (p<0.001). In contrast, there was no difference in c‐fos expression between SalA and saline vehicle treated rats, with the exception of the MnPO in which c‐fos expression was markedly increased (P<0.001).ConclusionThe ability of kappa opioid receptor agonists to increase diuresis and decrease osmolality may be associated with changes in c‐fos expression in the PVN and lamina terminalis. Previous studies in our lab, demonstrated a small increase in urine excretion rate following ICV administration of SalA and is consistent with the present findings in which there is a concomitant decrease in c‐fos expression in the magnocellular PVN and SON forebrain regions in SalA treated animals. However, the decrease was not a prominent as observed with U50488H, a synthetic KOR agonist. These results support the findings that the diuretic effects of SalA are not as potent as synthetic kappa opioid agonists.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Both Basal and Acute Restraint Stress-Induced c-Fos Expression Is Influenced by Age in the Extended Amygdala and Brainstem Stress Centers in Male Rats.

The hypothalamus-pituitary-adrenal axis (HPA) is the main regulator of the stress response. The key of the HPA is the parvocellular paraventricular nucleus of the hypothalamus (pPVN) controlled by higher-order limbic stress centers. The reactivity of the HPA axis is considered to be a function of age, but to date, little is known about the background of this age-dependency. Sporadic literature data suggest that the stress sensitivity as assessed by semi-quantitation of the neuronal activity marker c-Fos may also be influenced by age. Here, we aimed at investigating the HPA activity and c-Fos immunoreactivity 2 h after the beginning of a single 60 min acute restraint stress in eight age groups of male Wistar rats. We hypothesized that the function of the HPA axis (i.e., pPVN c-Fos and blood corticosterone (CORT) level), the neuronal activity of nine stress-related limbic areas (i.e., magnocellular PVN (mPVN), medial (MeA), central (CeA), basolateral nuclei of the amygdala, the oval (ovBNST), dorsolateral (dlBNST), dorsomedial (dmBNST), ventral and fusiform (fuBNST) divisions of the bed nucleus of the stria terminalis (BNST)), and two brainstem stress centers such as the centrally projecting Edinger-Westphal nucleus (cpEW) and dorsal raphe nucleus (DR) show age dependency in their c-Fos response. The somatosensory barrel cortex area (S1) was evaluated to test whether the age dependency is specific for stress-centers. Our results indicate that the stress-induced rise in blood CORT titer was lower in young age reflecting relatively low HPA activity. All 12 stress-related brain areas showed c-Fos response that peaked at 2 months of age. The magnitude of c-Fos immunoreactivity correlated negatively with age in seven regions (MeA, CeA, ovBNST, dlBNST, dmBNST, fuBNST and pPVN). Unexpectedly, the CeA, ovBNST and cpEW showed a considerable basal c-Fos expression in 1-month-old rats which decreased with age. The S1 showed a U-shaped age-related dynamics in contrast to the decline observed in stress centers. We conclude that the age- and brain area dependent dynamics in stress-induced neuronal activity pattern may contribute to the age dependance of the stress reactivity. Further studies are in progress to determine the neurochemical identity of neurons showing age-dependent basal and/or stress-induced c-Fos expression.

Oestradiol effects on neuroendocrine responses induced by water deprivation in rats.

Water deprivation (WD) induces changes in plasma volume and osmolality, which in turn activate several responses, including thirst, the activation of the renin-angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These systems seem to be influenced by oestradiol, as evidenced by the expression of its receptor in brain areas that control fluid balance. Thus, we investigated the effects of oestradiol treatment on behavioural and neuroendocrine changes of ovariectomized rats in response to WD. We observed that in response to WD, oestradiol treatment attenuated water intake, plasma osmolality and haematocrit but did not change urinary volume or osmolality. Moreover, oestradiol potentiated WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang II) concentrations. Immunohistochemical data showed that oestradiol potentiated vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and supraoptic (SON) nuclei but did not induce further changes in Fos expression in the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression, oestradiol increased OT mRNA expression in the SON and PVN under basal conditions and after WD, but did not induce additional changes in the mRNA expression for AVP in the SON or PVN. It also did not affect the mRNA expression of RAS components in the PVN. In conclusion, our results show that oestradiol acts mainly on the vasopressinergic system in response to WD, potentiating vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA expression.

Identification of CNS Sites Involved in the Cardiovascular and Renal Responses Elicited by Nociceptin/Orphanin FQ in Conscious Hypertensive Rats via c‐Fos Immunocytochemistry.

Intracerebroventricular (ICV) administration of the opioid‐like peptide agonist, nociceptin/Orphanin FQ (N/OFQ), produces a free water diuresis in addition to marked depressor effects on cardiovascular function and renal sympathetic nerve activity (RSNA). This study examined the changes in cFos expression in forebrain regions of angiotensin II high salt diet (ANGII) hypertensive rats following ICV administration of N/OFQ or saline vehicle. Protocol: 14 days prior to the experiment day, rats were implanted with an osmotic pump filled with angiotensin II and placed on a 2% high salt diet. At the day of the experiments, animals were placed in a metabolic cage and allowed to habituate for 3 hours. Following habituation, then two 15 minutes control periods, rats were than microinjected with either saline vehicle or nociceptin. Ninety minutes after the ICV injection, animals were perfused. Alternate sets of forebrain sections were processed for cFos using a commercially available antibody (Oncogene AB‐5). Results: ANGII treatment significantly increased cFos staining in the magnocellular and parvocellular PVN, SON, PNZ, OVLT, MPA and DMH brain sites as compared to Sham rats. ICV N/OFQ produced significant decrease in c‐Fos staining in the magnocellular PVN, SON, PNZ, OVLT, MPA and DMH of ANGII rats as compared to ANGII group microinjected with saline vehicle. Together, central N/OFQ receptor activation in these forebrain regions may contribute directly to or indirectly participate in the neuropathways involved in the cardiovascular and renal effects of N/OFQ. Supported by NIH 5SC2 HL104639

Differential regulation of TRPC4 expression in the magnocellular PVN and SON by hyperosmotic and hypoosmotic stress

Canonical Transient Receptor Potential Channel 4 (TRPC4) is expressed in the mammalian brain and has been implicated in dendritic neurotransmitter release. Our earlier reports have shown that TRPC4 is also expressed in the vasopressin (AVP) cells of the magnocellular (MNC) supraoptic nucleus (SON) and paraventricular nucleus (PVN). To investigate whether TRPC4 expression is regulated by changes in plasma osmolality, we utilized 2 models of osmotic stress ‐ bile duct ligation (BDL) induced hypoosmolality and water deprivation (WD) induced hyperosmolality. Immunoflourescent (IF) labeled TRPC4 positive cells in the SON was significantly increased after BDL (BDL 87 ± 8; SHAM 63 ± 5) and double IF for TRPC4 and AVP showed increased colocalization in the SON (BDL SON 56 ± 6; SHAM SON 36 ± 5). However, BDL did not influence TRPC4 IF in PVN. In contrast, WD did not change the number of TRPC4 IF cells in either SON or PVN. Laser capture microdissection (LCM) of 7–10 quick immunolabeled AVP neurons for RT‐PCR showed elevated TRPC4 mRNA in the SON of BDL rats, but not in the PVN (BDL 5.3 ± 1; SHAM 1.3 ± 0.6). WD reduced TRPC4 mRNA in SON and increased in PVN. Western blot analysis showed no changes in TRPC4 in either PVN or SON of WD rats, but showed increased TRPC4 in the SON but not PVN of BDL rats (BDL 3 ± 0.4; SHAM 1.8 ± 0.1). These results show that TRPC4 is differentially regulated by hypo and hyper osmotic stress in SON but not PVN. R01 HL062579.

Damage to the central amygdala produces differential encephalic c-fos expression in the water deprivation–partial rehydration protocol

We investigated the effects of electrolytic damage to the central nucleus of the amygdala on brain c-fos expression and 0.3 M NaCl intake of adult male rats ( n = 6–12/group) submitted to a cycle of 36 h of water deprivation (WD) followed by 2 h water intake until satiety or partial rehydration (PR). The groups were divided into sham lesion (CEAs), bilateral lesion of the CEA (CEAX) and misplaced lesion with intact CEA (CEAm). The WD–PR produced a marked increase in c-fos expression in the medial parabrachial nucleus (MPBN) and some increase in the parvocelullar portion of the hypothalamic paraventricular nucleus (PVNp), compared to respective hydrated control (no water deprivation) state in CEAX, but not in CEAs or CEAm. The WD–PR induced similar c-fos expression in the lamina terminalis, supraoptic nucleus, magnocellular PVN and lateral parabrachial nucleus in both CEAX and CEAs. The CEAX showed the typical reduced daily need-free 0.3 M NaCl intake compared to CEAs. However, the 0.3 M NaCl intake of CEAX, unexpectedly, was not significantly different from CEAs or intact rats in the sodium appetite test that followed a cycle of WD–PR. The results do not allow associating the alterations in c-fos expression to the typical inhibition of sodium appetite well known in the literature to be produced by damage to the CEA. Nevertheless, the enhanced cell activation in the MPBN and PVNp suggests an inhibitory role for the CEA on the activity of these nuclei when water-deprived rats have quenched their thirst.

Differential involvement of hypothalamic vasopressin neurons in multiple system atrophy

We sought to determine whether there is differential involvement of different groups of hypothalamic arginine-vasopressin (AVP) synthesizing neurons in multiple system atrophy (MSA). Hypothalamus was obtained from five subjects with clinical diagnosis of MSA confirmed neuropathologically and five age-matched controls. Sections were immunostained for AVP, and cells with visible nuclei were counted in the posterior portion of the paraventricular nucleus (PVNp), supraoptic nucleus (SON), magnocellular PVN and suprachiasmatic nucleus (SCN). Sections of the hypothalamus and medulla were also immunostained for tyrosine hydroxylase (TH). There was a significant loss of AVP neurons in the PVNp in MSA compared with controls (17 +/- 3 versus 59 +/- 10 cells/section, P < 0.01). There was preservation of AVP- and TH-immunoreactive neurons in the SON and magnocellular PVN in all MSA cases. In contrast, there was marked depletion of TH-immunoreactive fibres innervating these magnocellular AVP neurons, coincident with a loss of neurons in the A1 area (6 +/- 1 versus 13 +/- 1 cells/section, P < 0.01). There was loss of AVP neurons in the SCN in MSA compared with control cases (14 +/- 3 versus 71 +/- 16 cells/section, P < 0.02). Our results indicate that, in MSA, loss of AVP neurons in the PVNp may contribute to sympathetic failure, whereas loss of catecholaminergic input from the brainstem to the magnocellular AVP neurons may contribute to impaired AVP secretion in response to orthostatic stress. Loss of AVP neurons in the SCN may contribute to impaired circadian regulation of endocrine and autonomic functions.

Differential actions of acute and chronic citalopram on the rodent hypothalamic–pituitary–adrenal axis response to acute restraint stress

Serotonin re-uptake inhibitors (SSRIs) can affect the basal activity of the hypothalamic-pituitary-adrenal (HPA) axis in rats. A single injection of citalopram has been shown to stimulate the HPA axis while repeated administration leads to attenuation of the corticosterone response to the SSRI. The purpose of this work was to investigate the rodent HPA axis response to restraint stress, following acute and chronic treatment with the SSRI citalopram. We have demonstrated that a single injection of citalopram is able to prolong acute restraint-induced increases in plasma levels of corticosterone and adrenocorticotrophin (ACTH). This is possibly mediated by arginine vasopressin (AVP) in the parvocellular cells of the paraventricular nucleus (pPVN), as treatment with citalopram or restraint alone did not increase AVP mRNA in pPVN while the combination of treatments resulted in a significant increase in AVP mRNA in the pPVN. In contrast, the increase in corticotrophin-releasing factor (CRF) mRNA in the pPVN in response to acute restraint stress was not altered by citalopram. Oxytocin (OT) mRNA was also increased in the magnocellular PVN (mPVN) by the solo treatments of citalopram and restraint, and was not further enhanced by the dual treatment of restraint and citalopram. Chronic treatment with citalopram did not alter basal plasma levels of corticosterone or ACTH. However, the ACTH response to acute restraint was attenuated following chronic citalopram treatment. AVP mRNA in the pPVN was significantly elevated in response to chronic citalopram compared with saline controls suggesting an effect mediated through the AVP subset of pPVN neurones. The CRF mRNA response to acute restraint was not altered in rats treated chronically with citalopram. OT mRNA was not enhanced in the mPVN following chronic infusion of citalopram but was increased by acute restraint stress. We conclude from these data that both acute and chronic citalopram treatment has the potential to alter the rodent response to acute restraint stress. These effects appear to be regulated by the AVP-containing subset of CRF neurons in the pPVN and thus suggest that parvocellular AVP may have an important role in mediating the actions of SSRIs.

NPY and cohorts in regulating appetite, obesity and metabolic syndrome: beneficial effects of gene therapy.

Neuropeptide Y is the most potent physiological appetite transducer known. The NPY network is the conductor of the hypothalamic appetite regulating orchestra in the arcuate nucleus-paraventricular nucleus (ARC-PVN) of the hypothalamus. NPY and cohorts, AgrP, GABA and adrenergic transmitters, initiate appetitive drive directly through Y1, Y5, GABAA and alpha1 receptors, co-expressed in the magnocellular PVN (mPVN) and ARC neurons and by simultaneously repressing anorexigenic melanocortin signaling in the ARC-PVN axis. The circadian and ultradian rhythmicities in NPY secretion imprint the daily circadian and episodic feeding patterns. Although a number of afferent hormonal signals from the periphery can directly modulate NPYergic signaling, the reciprocal circadian and ultradian rhythmicities of anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding pattern of NPY discharge for daily meal patterning. Subtle and progressive derangements produced by environmental and genetic factors in this exquisitely intricate temporal relationship between the two opposing humoral signals and the NPY network promote hyperphagia and abnormal rate of weight gain culminating in obesity and attendant metabolic disorders. Newer insights at cellular and molecular levels demonstrate that a breakdown of the integrated circuit due both to high and low abundance of NPY at target sites, underlies hyperphagia and increased adiposity. Consequently, interruption of NPYergic signaling at a single locus with NPY receptor antagonists may not be the most efficacious therapy to suppress hyperphagia and obesity. Central leptin gene therapy in rodents has been shown to subjugate, i.e. bring under homeostatic control, NPYergic signaling and suppress the age-related and dietary obesity for extended periods and thus shows promise as a newer treatment modality to curb the pandemic of obesity and metabolic syndrome.

Osmotic regulation of estrogen receptor-beta expression in magnocellular vasopressin neurons requires lamina terminalis.

Estrogen receptor-beta (ER-beta) expression in rat magnocellular vasopressin (VP) neurons of the supraoptic and paraventricular nuclei (SON and PVN, respectively) becomes undetectable after 72 h of 2% NaCl consumption. To test the hypothesis that osmosensitive mechanisms that originate in the region of the organum vasculosum lamina terminalis (OVLT) control ER-beta expression in the SON and PVN, animals were water deprived after electrolytic lesions were performed on the area anterior to the ventral third ventricle (AV3V). Such lesions prevent osmotic stimulation of VP release. Four weeks after surgery, male rats [lesioned (n = 16) or sham (n = 14)] were water deprived for 48 h or allowed water ad libitum. Water deprivation eliminated ER-beta-immunoreactivity (-ir) in SON and magnocellular PVN of sham-lesioned animals. Fos-ir was evident in these neurons, and plasma osmolality (Posm) and hematocrit (Ht) were significantly elevated compared with the sham-hydrated rats (Posm, 304 +/- 1 vs. 318 +/- 2 mosmol/kgH2O; P < 0.001; Ht, 49.6 +/- 0.6 vs. 55.0 +/- 0.9%; P < 0.001). ER-beta expression was comparable in sham-hydrated, AV3V-hydrated, and 6 of 8 AV3V-dehydrated rats despite significant increases in Posm in both groups (AV3V hydrated, 312 +/- 2; AV3V dehydrated, 380 +/- 10 mosmol/kgH2O; P < 0.001). OVLT was not ablated in the AV3V-dehydrated rats in which ER-beta was depleted. Fos-ir was low or undetectable in SON in the AV3V-hydrated animals despite elevated Posm values. In AV3V-dehydrated rats, Fos-ir was significantly less than in sham-dehydrated animals but was significantly increased compared with the sham-hydrated group. This could reflect activation by nonosmotic parameters that do not inhibit ER-beta expression. These data support the hypothesis that inhibition of ER-beta expression in the SON by osmotic stimulation is mediated by osmoreceptive neurons in the lamina terminalis.

Immunolabeling reveals cellular localization of the N-methyl-D-aspartate receptor subunit NR2B in neurosecretory cells but not astrocytes of the rat magnocellular nuclei.

Previous studies suggest that activation of N-methyl-D-aspartate (NMDA) receptors facilitates phasic firing and spike clustering displayed by magnocellular neuroendocrine cells (MNCs) of the supraoptic (SON) and paraventricular nucleus of the hypothalamus (PVN). Osmotic stimulation produces similar activity patterns which, in turn, can lead to enhanced release of vasopressin and oxytocin from MNCs. Our laboratory has shown that dehydration regulates the expression of the NMDA receptor subunits, NR1 and NR2B, in the SON and PVN, suggesting their involvement in osmoregulation. In the present study, we examined the cellular localization of NR2B, one of the glutamate-binding subunits of the NMDA receptor, with an NR2B-specific antibody. Using double-label immunohistochemistry and three different detection methods with metallic, peroxidase, and fluorescence markers, it was found that both vasopressin and oxytocin-producing MNC populations synthesize NR2B. The incidence of NR2B colocalization with vasopressin-neurophysin in the SON and lateral magnocellular PVN (PVL) was 0.95 and 0.91, respectively. For oxytocin-neurophysin, the corresponding values were 0.97 and 0.95, respectively. Furthermore, the extent of colocalization in MNCs of the SON, PVL, retrochiasmatic SON, and accessory neurosecretory nuclei was similar. Astrocytes associated with the SON, and identified with antibodies targeting glial fibrillary acidic protein (GFAP) or vimentin, were not colabeled with NR2B. Our results demonstrate that NR2B protein is expressed by almost all MNCs and that it is equally prevalent in vasopressinergic and oxytocinergic populations of various magnocellular neuroendocrine nuclei supporting a role of NMDA receptors in MNC-mediated neurosecretory processes. Although NR2B may form part of functional NMDA receptors on MNCs, it is probably not present on astrocytes associated with nearby MNCs.

Neural substrates for leptin and neuropeptide Y (NPY) interaction: hypothalamic sites associated with inhibition of NPY-induced food intake

YOKOSUKA M., B. XU, S. PU, P. S. KALRA AND S. P. KALRA. Neural Substrates for Leptin and NPY Interaction: Hypothalamic Sites Associated with Inhibition of NPY-Induced Food Intake. PHYSIOL BEHAV 64(3) 331–338, 1998.—Intracerebroventricular (i.c.v.) injection of leptin, the adipocyte hormone, inhibits neuropeptide Y (NPY)-induced feeding in the rat. To identify the neural substrate for leptin and NPY interaction in the hypothalamus, we evaluated the expression of c-fos-like immunoreactivity (FLI), an early marker of neuronal activation, in response to icv administration of leptin, NPY and leptin plus NPY. As expected, leptin significantly decreased NPY-induced feeding in leptin plus NPY-treated rats. A comparative evaluation of the number of FLI-positive neurons in hypothalamic sites showed that both leptin and NPY activated FLI in the parvocellular subdivision of the paraventricular nucleus (pPVN), dorsomedial nucleus (DMN) and ventromedial nucleus (VMN). NPY also augmented the FLI response in the magnocellular PVN (mPVN) and supraoptic nucleus (SON), two sites where leptin alone was ineffective. Combined leptin and NPY treatment significantly decreased the number of FLI-positive neurons in the magnocellular PVN but increased their number in the dorsomedial nucleus as compared to the number of FLI-expressing neurons in these sites after NPY and leptin alone. Because there is morphologic evidence of a link between magnocellular PVN and dorsomedial nucleus, these results suggest the functional involvement of leptin plus NPY responsive elements in these sites in reduction of NPY-induced feeding by leptin.

Reduced NMDA receptor sensitivity may underlie the resistance of subpopulations of PVN neurons to excitotoxicity.

Magnocellular neurons in the paraventricular nucleus are resistant to excitotoxic cell damage. We tested the hypothesis that a modified post-synaptic response following NMDA receptor activation may underlie this resistance. Whole-cell recordings from hypothalamic slices showed that NMDA receptor activation caused dose-dependent depolarizations in both Type I (putative magnocellular) and Type II (putative parvocellular) neurons. Type II cells, however, were an order of magnitude more sensitive (10 nM) than Type I neurons (100 nM). The depolarizations recorded in Type II cells were also significantly greater (> 35% resulting in sodium channel inactivation) than those recorded in Type I neurons. This differential sensitivity of neurons to NMDA receptor activation may explain the selective resistance of magnocellular PVN neurons to excitatory neurotoxins.

Enkephalin in the Rat Neural Lobe: Immunocytochemical Evidence for its Presence Within Synaptic Elements on Pituicytes

Publisher Summary In the following years, the conclusion was drawn that the hypothalamo-neurohypophyseal system (HNS) contains vasopressin (VP), adiuretin, and oxytocin (OXT). Moreover, these hormones are accompanied by proteins called neurophysins, from which they could be liberated. Until the mid-seventies, nobody doubted the idea that VP and OXT are the hormones that are exclusively synthetized, transported, and released within the mammalian HNS. However, in the past few years, mainly due to the application of immunocytochemistry (ICC), the number of compounds reported to be present within the rat magnocellular PVN and SON increased tremendously. Most of these compounds have also been demonstrated in the neural lobe, which is logical, because it is one of the main projection sites of the SON. In addition, several of these compounds would coexist with VP or OXT. Unfortunately, most of these compounds have been demonstrated solely by ICC, which has its pitfalls. This chapter attempts to sum up and subsequently integrate the progress in biochemical, pharmacological and immunocytochemical research on opioid peptides in the neural lobe that has been achieved in the past few years.