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J P Herman

Publications and source records attributed to J P Herman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Local integration of glutamate signaling in the hypothalamic paraventricular region: regulation of glucocorticoid stress responses.

The present study is a test of the hypothesis that endogenous glutamatergic input to the hypothalamic paraventricular nucleus (PVN) is involved in stress-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. We examined whether corticosterone (CORT) responses to restraint stress could be attenuated by bilateral 50 nl microinjections of kynurenic acid (KYN, ionotropic glutamate receptor antagonist) into the medial PVN of conscious rats. Immediately following microinjection, rats were subjected to 30 min restraint, and stress-induced plasma CORT was measured at 30, 60, 120, and 180 min following the onset of restraint. KYN (50 pmol) significantly reduced cumulative CORT responses to acute restraint stress by 24%. In contrast, microinjections centered dorsal to the PVN increased CORT responses by 31%, suggestive of a disinhibition of local PVN-inhibitory input. KYN injections immediately anterior, ventral, or posterior to the PVN had no effect, suggesting an absence of potential diffusion artifacts. These results provide evidence that endogenous glutamate in the PVN and surrounding peri-PVN region plays a physiologically significant role in both generating and limiting glucocorticoid stress responses in awake rats.

Animals↗
PubMed1999

Anatomical and functional reconstruction of the nigrostriatal system in vitro: selective innervation of the striatum by dopaminergic neurons.

To study development of the nigrostriatal pathway in an in vitro model system, organotypic slices obtained from rat pups (P4) and containing the striatum and the cortex were grown together with apposed embryonic (E13.5) mesencephalic blocks according to the static slice culture method of Stoppini et al. (1991; J. Neurosci. Methods 37:173-182). Under these conditions, mesencephalic dopaminergic (DA) fibers rapidly grow through the slice, preferentially its striatal portion. This innervation provides a true synaptic innervation to the striatum, as shown by the presence of DA terminals on striatal neurons. DA fibers are able to exert a functional influence, as seen by their ability to modulate c-Fos expression in striatal neurons in the same way as in vivo. Thus, blockade, under basal conditions, of the effect of spontaneously released dopamine by the D2 receptor antagonist haloperidol leads to the activation of c-Fos expression in the striatum. Furthermore, stimulation of DA release by amphetamine induces striatal c-Fos expression in a D1 receptor-dependent manner. Next, the mechanisms of the selective striatal innervation were examined. Indeed, DA fibers innervated specifically the striatum, avoiding the cortical portion of the slice. This selectivity seems to be specific for DA neurons; no selectivity could be observed when noradrenergic neurons were substituted for DA neurons. Short-term cocultures in a collagen gel of mesencephalic blocks with striatal blocks failed to reveal any oriented outgrowth of DA fibers from the mesencephalon, suggesting that the selective innervation observed in the organotypic slices results from some contact-dependent, presumably adhesive interactions rather than from the presence of some diffusible substance orienting the growth of DA fibers towards the striatum. On the other hand, DA neurons seeded onto striatal slices did not attach selectively onto the striatal portion of the slice, indicating that the putative specific adhesive interactions governing the selective striatal innervation are not the same as those determining the adhesion of the DA neurons. These results show that cocultures of cortex-striatum and mesencephalic slices result in a system that displays a number of the morphological and functional traits of the normal nigrostriatal system and that can be relied on as a good in vitro model of in vivo development.

Animals↗
PubMed1999

Differential forebrain c-fos mRNA induction by ether inhalation and novelty: evidence for distinctive stress pathways.

Previous studies indicate the existence of subtypes of stressors invoking distinct patterns of neuronal integration. Pathways activated by stress appear to depend on whether the perceived threat is processive/neurogenic or systemic in nature. To test this hypothesis, the present study compares magnitude and extent of c-fos mRNA induction in response to novelty (open field (OF), representing a processive stressor) or ether exposure (representing a systemic stressor). Exposure to the OF or ether fumes both produced increases in plasma corticosterone (CORT) levels; notably, peak levels of secretion were elevated in the ether group, suggestive of augmented HPA secretory activity to this stressor. In situ hybridization analysis of c-fos mRNA induction reveals common and divergent activational properties in the two stress groups. The extent of c-fos mRNA expression was similar in the paraventricular nucleus (PVN), despite stress-related differences in CORT secretion. Analysis of the dorsomedial hypothalamic nucleus, suprachiasmatic nucleus (SCN) and limbic sites, specifically, the lateral septum and medial amygdaloid nucleus, indicate greater c-fos mRNA induction in animals exposed to OF stress. The frontoparietal cortex was only forebrain region showing differential activation by ether. Differential c-fos induction was not observed in the medial preoptic area (ventrolateral quadrant), paraventricular thalamus, dorsolateral striatum or hippocampus. The results indicate that processive and systemic stressors differ not only in the patterning of neuronal activation in the CNS, but also in the extent to which selected stress-sensitive regions are induced.

Amygdala↗
PubMed1999

Central peptidergic neurons are hyperactive during collateral sprouting and inhibition of activity suppresses sprouting.

Little is known regarding the effect of chronic changes in neuronal activity on the extent of collateral sprouting by identified CNS neurons. We have investigated the relationship between activity and sprouting in oxytocin (OT) and vasopressin (VP) neurons of the hypothalamic magnocellular neurosecretory system (MNS). Uninjured MNS neurons undergo a robust collateral-sprouting response that restores the axon population of the neural lobe (NL) after a lesion of the contralateral MNS (). Simultaneously, lesioned rats develop chronic urinary hyperosmolality indicative of heightened neurosecretory activity. We therefore tested the hypothesis that sprouting MNS neurons are hyperactive by measuring changes in cell and nuclear diameters, OT and VP mRNA pools, and axonal cytochrome oxidase activity (COX). Each of these measures was significantly elevated during the period of most rapid axonal growth between 1 and 4 weeks after the lesion, confirming that both OT and VP neurons are hyperactive while undergoing collateral sprouting. In a second study the hypothesis that chronic inhibition of neuronal activity would interfere with the sprouting response was tested. Chronic hyponatremia (CH) was induced 3 d before the hypothalamic lesion and sustained for 4 weeks to suppress neurosecretory activity. CH abolished the lesion-induced increases in OT and VP mRNA pools and virtually eliminated measurable COX activity in MNS terminals. Counts of the total number of axon profiles in the NL revealed that CH also prevented axonal sprouting from occurring. These results are consistent with the hypothesis that increased neuronal activity is required for denervation-induced collateral sprouting to occur in the MNS.

Animals↗
PubMed1999

Evidence that IGF-I acts as an autocrine/paracrine growth factor in the magnocellular neurosecretory system: neuronal synthesis and induction of axonal sprouting.

The ability of mature oxytocinergic (OT) and vasopressinergic (VP) neurons of the magnocellular neurosecretory system (MNS) to undergo axonal growth implies that one or more growth factors may be active in the adult MNS, yet little is known regarding their possible identity. One such potential factor is insulin-like growth factor I (IGF-I). We have examined the expression of IGF-I mRNA and IGF-I-immunoreactivity (IGF-I-ir) in the mature MNS and have also determined the in vivo response of OT and VP neurons to hypothalamic implants of IGF-I. In situ hybridization revealed moderate labeling of IGF-I mRNA in both the supraoptic (SON) and the paraventricular (PVN) nuclei of adult male rats. RT-PCR analysis confirmed the presence of authentic IGF-I mRNA in extracts of the basal hypothalamus. Faint IGF-I-ir was detected in scattered magnocellular neurons within both the PVN and the SON of normal rats, but IGF-I-ir was much more intense and the majority of MNS neurons including those in the accessory nuclei were immunoreactive in sections from rats given colchicine, as were some parvocellular neurons in the PVN. Confocal microscopy revealed that IGF-I-ir was present in both OT and VP neurons, but VP neurons contained the most intense IGF-I-ir. Finally, a dramatic growth response of OT but not of VP fibers was observed following implantation of polymer rods containing IGF-I into the hypothalamus. A dense OT fiber plexus grew along the cannula track and OT fibers invaded the leptomeninges ventral to the SON and encircled the rostral cerebral artery. To our knowledge this is the first demonstration of axonal sprouting by mature OT neurons in response to an identified growth factor and the first direct demonstration of sprouting in response to exogenous IGF-I in the adult CNS. These findings suggest that IGF-I is synthesized and transported by adult MNS neurons where it may act as an autocrine and/or paracrine growth factor.

Animals↗
PubMed1999

Excitatory influence of the locus coeruleus in hypothalamic-pituitary-adrenocortical axis responses to stress.

The locus coeruleus (LC) is a key brainstem region involved in arousal and is highly responsive to alerting/stressful stimuli, including those that activate the hypothalamic-pituitary-adrenocortical (HPA) axis. It is currently unclear whether the LC exerts any regulatory influence on the HPA axis and, consequently, on neuroendocrine responses to stress. The present studies were designed to test the hypothesis that the LC promotes HPA axis responses to acute and chronic stress. Adult male rats received bilateral (6-hydroxydopamine) lesions of the LC that produced severe cell loss in the LC and 80% depletion of noradrenaline in medial prefrontal cortex. Notably, lesions did not affect dopamine-beta-hydroxylase protein content in the parvocellular paraventricular nucleus (PVN), indicating a lack of collateral damage to other ascending noradrenergic pathways. LC lesions significantly reduced peak adrenocorticotropic hormone (ACTH) and corticosterone responses to 30 min acute restraint stress. However, LC lesions did not significantly attenuate neuroendocrine or other physiological responses to a 4-week chronic variable stress regimen. LC lesions did not substantially affect basal concentrations of plasma corticosterone or corticotropin-releasing hormone mRNA expression in the hypothalamic paraventricular nucleus following chronic stress. We conclude that the LC is a HPA-excitatory brain region, promoting neuroendocrine and physiological responses primarily to acute stress. However, a potential role for the LC in the induction of HPA axis hyperactivity following chronic stress can not be ruled out.

Acute Disease↗
PubMed1999

Defense of adrenocorticosteroid receptor expression in rat hippocampus: effects of stress and strain.

Neuronal mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) proteins are glucocorticoid-activated transcription factors that bind identical DNA response elements yet transduce distinct physiological/transcriptional actions. The present study assessed regulation of adrenocorticosteroid receptor RNA and protein following intermittent stress exposure, using Sprague Dawley (S-D) and stress-hyperresponsive Fischer 344 (F344) rat strains. The F344 (but not S-D) strain showed enhanced acute stress responsivity and enhanced corticosterone secretion following prolonged stress. F344 rats also showed reduced responsiveness to a novel stressor after prolonged stress exposure, suggestive of enhanced glucocorticoid negative feed-back. Upon prolonged stress, F344 rats down-regulated MR hnRNA in CA1, CA3, and dentate gyrus. Transcriptional changes were accompanied by decreased expression of the alpha 5' messenger RNA (mRNA) form, consistent with altered promoter utilization. In contrast, alpha 5' splice variant, full-length mRNA, and MR protein expression were not affected by stress in either strain, implying that transcriptional changes do not affect overall mRNA or protein expression. GR protein was increased in pyramidal and granule cell somata/nuclei of F344 rats despite lack of a change in mRNA expression. These data suggest that prolonged stress elicits restricted changes in MR and GR expression in the F344 strain only. Overall, stable expression of adrenocorticosteroid receptors is rigorously defended in hippocampal neurons, apparently through transcriptional and posttranscriptional mechanisms.

Animals↗
PubMed1998

Regulation of hippocampal glucocorticoid receptor gene transcription and protein expression in vivo.

Glucocorticoid receptors (GRs) are glucocorticoid-activated transcription factors that modulate expression of a variety of neuronal genes. Appropriate control of GR expression is therefore critical for maintenance of cellular and organismic homeostasis. The present study assessed glucocorticoid regulation of the GR at the gene, mRNA, and protein level. Removal of circulating glucocorticoids (adrenalectomy) increased GR mRNA expression in CA1 and dentate gyrus (DG). Corticosterone (CORT) replacement normalized GR mRNA expression, whereas high doses slightly decreased GR mRNA in CA1. Parallel increases were observed using a probe complementary to the distal 3' untranslated region, indicating that mRNA changes were not attributable to selection of alternative polyadenylation site. Expression of a GR intronic sequence was also increased by adrenalectomy, consistent with increased gene transcription. Analysis of regional GR protein expression by immunoautoradiography did not reveal changes in GR protein in pyramidal cell layers; however, increased GR signal was seen in the stratum radiatum, indicating redistribution of GR to the cytosol. Western blot analysis confirmed adrenalectomy-induced increases in hippocampal GR levels. Administration of the mineralocorticoid receptor (MR) antagonist spironolactone increased both GR mRNA and protein in CA1 and DG, consistent with MR-mediated inhibition of GR transcription. However, high-dose CORT treatment did not decrease GR mRNA or protein levels. Chronic stress exposure did not downregulate GR mRNA or protein in hippocampus. The results suggest that the hippocampal GR is subject to heterologous regulation by the MR. In contrast, GR autoregulation is only evident during prolonged exposure to high-circulating glucocorticoid levels.

Adrenal Glands↗
PubMed1998

Mineralocorticoid receptors regulate bcl-2 and p53 mRNA expression in hippocampus.

The present study addressed the hypothesis that the neuronal mineralocorticoid receptor (MR) regulates genes associated with cell death, such as bax and p53, and cell viability, including bcl-2, BDNF, and NT-3. Rats were pretreated with either oil vehicle or the MR antagonist spironolactone (SPIRO) and subsequently injected with saline or kainic acid (KA). MR blockade significantly decreased basal mRNA expression of bcl-2 in CA1 of saline-treated animals and attenuated KA-induced increases in p53 mRNA levels in CA3. SPIRO pretreatment had no significant effect on expression of bax, NT-3, or BDNF mRNAs. The data suggest that the neuronal MR contributes to regulation of select cell survival and cell death-related genes in hippocampal pyramidal neurons.

Animals↗
PubMed1998

Region-specific regulation of glutamic acid decarboxylase (GAD) mRNA expression in central stress circuits.

Neurocircuit inhibition of hypothalamic paraventricular nucleus (PVN) neurons controlling hypothalamo-pituitary-adrenocortical (HPA) activity prominently involves GABAergic cell groups of the hypothalamus and basal forebrain. In the present study, stress responsiveness of GABAergic regions implicated in HPA inhibition was assessed by in situ hybridization, using probes recognizing the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD65 and GAD67 isoforms). Acute restraint preferentially increased GAD67 mRNA expression in several stress-relevant brain regions, including the arcuate nucleus, dorsomedial hypothalamic nucleus, medial preoptic area, bed nucleus of the stria terminalis (BST) and hippocampus (CA1 and dentate gyrus). In all cases GAD67 mRNA peaked at 1 hr after stress and returned to unstimulated levels by 2 hr. GAD65 mRNA upregulation was only observed in the BST and dentate gyrus. In contrast, chronic intermittent stress increased GAD65 mRNA in the anterior hypothalamic area, dorsomedial nucleus, medial preoptic area, suprachiasmatic nucleus, anterior BST, perifornical nucleus, and periparaventricular nucleus region. GAD67 mRNA increases were only observed in the medial preoptic area, anterior BST, and hippocampus. Acute and chronic stress did not affect GAD65 or GAD67 mRNA expression in the caudate nucleus, reticular thalamus, or parietal cortex. Overall, the results indicate preferential upregulation of GAD in central circuitry responsible for direct (hypothalamus, BST) or multisynaptic (hippocampus) control of HPA activity. The distinct patterns of GAD65 and GAD67 by acute versus chronic stress suggest stimulus duration-dependent control of GAD biosynthesis. Chronic stress-induced increases in GAD65 mRNA expression predict enhanced availability of GAD65 apoenzyme after prolonged stimulation, whereas acute stress-specific GAD67 upregulation is consistent with de novo synthesis of active enzyme by discrete stressful stimuli.

Acute Disease↗
PubMed1998

Ventral subiculum regulates hypothalamo-pituitary-adrenocortical and behavioural responses to cognitive stressors.

The hippocampus plays an important role in central stress integration. The present study tests the hypothesis that the ventral subiculum, as a principal source of hippocampal efferents, is involved in co-ordination of hypothalamo-pituitary-adrenocortical and behavioural responses to cognitively-processed information. Basal hypothalamo-pituitary-adrenocortical activation appears to be normal in ventral subiculum lesion rats, as basal corticosterone and adrenocorticotropic hormone secretion, anterior pituitary pro-opiomelanocortin and type 1 corticotropin-releasing hormone receptor messenger RNA expression, adrenal and thymus weight, and splenic mitogen activity are not affected by lesion. Lesions of the ventral subiculum induce glucocorticoid hypersecretion following restraint stress or open field exposure, whereas responses to ether inhalation are unaffected. Interestingly, ventral subiculum lesion does not affect fast glucocorticoid negative feedback inhibition of restraint-induced adrenocorticotropic hormone release. Corticotropin-releasing hormone immunoreactivity is increased in the hypothalamic paraventricular nucleus of ventral subiculum lesion rats, and is differentially depleted by acute stress exposure (relative to sham-lesion rats). However, ventral subiculum lesion does not affect basal and stress-induced corticotropin-releasing hormone, arginine vasopressin and cFOS messenger RNA expression in paraventricular nucleus neurons. Behavioural analysis reveals that ventral subiculum lesion rats are hyper-responsive to open field exposure, showing decreased total ambulation and reduced incidence of central square entry. The results suggest that the ventral subiculum plays a specific role in integrating cognitively-processed stimuli (e.g., restraint and open field exposure) into appropriate neuroendocrine and behavioural responses to stress. Enhanced stress-induced glucocorticoid secretion and increased corticotropin-releasing hormone biosynthesis are likely due to removal of oligosynaptic inhibitory input to the paraventricular nucleus subsequent to ventral subiculum lesion.

Adrenocorticotropic Hormone↗
PubMed1998

Anatomical interactions between the central amygdaloid nucleus and the hypothalamic paraventricular nucleus of the rat: a dual tract-tracing analysis.

Axonal connections between the amygdala and the hypothalamic paraventricular nucleus were examined by combined anterograde-retrograde tract tracing. Iontophoretic injections of the retrograde tracer Fluorogold were placed in the paraventricular nucleus, and the anterograde tracer PHA-L in the ipsilateral central or medial amygdaloid nuclei. Single and double-label immunohistochemistry were used to detect tracers. Single label anterograde and retrograde tracing suggest limited evidence for direct connections between the central or medial amygdala and the paraventricular nucleus. In general, scattered PHA-L-positive terminals were seen in autonomic subdivisions of the paraventricular nucleus (lateral parvocellular, dorsal parvocellular and ventral medial parvocellular subnuclei) following central or medial amygdaloid nucleus injection. Double-label studies indicate that central and medial amygdaloid nucleus efferents contact paraventricular nucleus-projecting cells in several forebrain nuclei. In the case of central nucleus injections, PHA-L positive fibers occasionally contacted Fluorogold-labeled neurons in the anteromedial, ventromedial and preoptic subnuclei of the bed nucleus of the stria terminalis. Overall, such contacts were quite rare, and did not occur in the bed nucleus of the stria terminalis regions showing greatest innervation by the central amygdaloid nucleus. In contrast, medial amygdala injections resulted in a significantly greater overlap of PHA-L labeling and Fluorogold-labeled neurons, with axosomatic appositions observed in medial divisions of the bed nucleus of the stria terminalis, anterior hypothalamic area and preoptic area. The results provide anatomical evidence that a substantial proportion of amygdaloid connections with hypophysiotrophic paraventricular nucleus neurons are likely multisynaptic, relaying in different subregions of the bed nucleus of the stria terminalis and hypothalamus.

Amygdala↗
PubMed1997

Striatal target-induced axonal branching of dopaminergic mesencephalic neurons in culture via diffusible factors.

The effects of striatal target cells on the morphological development of dopaminergic neurons were studied in dissociated cultures of embryonic rat mesencephalon. Mesencephalic neurons were cultured for four days in presence of target striatal cells or non target cerebellar ones. The outgrowth of dopaminergic neurons, visualized after tyrosine hydroxylase immunohistochemistry, was examined by quantitative morphometry. In cocultures, the increased complexity of dopaminergic neurites (branching) was the most striking pattern. It was dependent on the presence of target striatal cells as compared to non target ones. Cultures raised in presence or absence of serum lead to suggest the implication of striatal neurons rather than glia. Using MAP2 and phosphorylated neurofilaments immunohistochemistry in combination with tyrosine hydroxylase immunolabelling, it could be shown that the target-induced branching effect concerned only axonal and not dendritic processes. To further define whether diffusible factors from the striatal target would participate in the axonal branching effect, mesencephalic cells were cultured in conditioned medium from striatal neurons. Striatal conditioned medium enhanced dopamine uptake and dopamine neuron branching to the same extent as that observed in striatal cocultures. These findings demonstrate that soluble factors secreted by striatal neurons themselves selectively influence the branching of dopaminergic axons in vitro.

Animals↗
PubMed1997

Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis.

Integration of the hypothalamo-pituitary-adrenal stress response occurs by way of interactions between stress-sensitive brain circuitry and neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN). Stressors involving an immediate physiologic threat ('systemic' stressors) are relayed directly to the PVN, probably via brainstem catecholaminergic projections. By contrast, stressors requiring interpretation by higher brain structures ('processive' stressors) appear to be channeled through limbic forebrain circuits. Forebrain limbic sites connect with the PVN via interactions with GABA-containing neurons in the bed nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final elaboration of processive stress responses is likely to involve modulation of PVN GABAergic tone. The functional and neuroanatomical data obtained suggest that disease processes involving inappropriate stress control involve dysfunction of processive stress pathways.

Adrenal Cortex↗
PubMed1997

Expression of insulin-like growth factor binding protein-2 during postnatal development of the rat neurointermediate pituitary.

The expression of insulin-like growth factor binding protein-2 (IGFBP-2) during postnatal development of the rat neurointermediate pituitary was characterized using immunocytochemistry and in situ hybridization. Glial cells in the neural lobe (NL) showed robust expression of IGFBP-2 throughout the postnatal period and continuing into adulthood. These were identified as pituicytes by the presence of S-100 protein; IGFBP-2 was not present in microglia in the NL. IGFBP-2 immunoreactivity was more punctate in mature pituicytes, suggesting a possible association with the cell membrane. No expression of IGFBP-2 by brain astrocytes was observed at any age examined, even in regions such as the median eminence and subfornical organ that lack a blood-brain barrier. IGFBP-2 was also localized immunocytochemically in melanotropes and glial-like cells of the intermediate lobe (IL). Positive cells were most numerous in neonates and declined thereafter, with immunoreactivity undetectable by 65 days of age. IGFBP-2 mRNA was detected in the IL only at 1 day of age. These findings are consistent with a potential role for IGFBP-2 in modulating effects of the insulin-like growth factors during development of the neurointermediate lobe. The constitutive expression of high levels of IGFBP-2 by mature pituicytes also suggests that this protein could be secreted and/or influence a variety of processes in the mature NL, such as glial proliferation, axonal growth, or morphological plasticity of pituicytes.

Animals↗
PubMed1996

Localization of natriuretic peptide-activated guanylate cyclase mRNAs in the rat brain.

Physiological actions of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are elaborated by membrane-bound natriuretic peptide receptors (NPRs). These receptors possess intracellular guanylate cyclase domains that mobilize cyclic guanosine monophosphate upon binding of peptide. Two distinct NPR subtypes have been described in brain: the NPR-A selectively binds ANP, whereas NPR-B exhibits high affinity for CNP. To define further the potential domains of ANP and CNP action in brain, the present study used in situ hybridization histochemistry to map NPR-A and NPR-B mRNA-expressing cell populations. Significant levels of neuronal NPR-A mRNA expression were observed only in the mitral cell layer of the olfactory bulb, medial habenula, subfornical organ, and area postrema. Expression of NPR-A mRNA was observed in forebrain white matter tracts, suggesting synthesis in glial cells. In contrast, NPR-B mRNA was widely expressed throughout the neuraxis. In the telencephalon, signal was abundant throughout limbic cortex and neocortex, olfactory bulb, hippocampus, and amygdala. Intense NPR-B mRNA hybridization was observed in preoptic-hypothalamic neuroendocrine circuits and in motor nuclei of cranial nerves. Intermediate expression of NPR-B mRNA was observed in brainstem nuclei controlling autonomic function. Labeling for NPR-B but not NPR-A mRNA was observed in pituicytes in the neural lobe of the pituitary and in scattered cells of the anterior pituitary. These results suggest that CNP is the primary biologically active natriuretic peptide in brain. In contrast with NPR-B, NPR-A appears to be expressed largely in restricted cell populations containing high levels of ANP and in circumventricular organs. These data implicate the NPR-A in autoregulation of ANP neurons and central registration of cardiac ANP release.

Animals↗
PubMed1996

Changes in striatal immediate early gene expression following neonatal dopaminergic lesion and effects of intrastriatal dopaminergic transplants.

To evaluate the functional integration of neonatal dopaminergic transplants within host brain we studied the postsynaptic effects induced by their stimulation by following the expression of immediate early genes c-fos, c-jun and egr-1. This study was conducted nine months after the intrastriatal implantation of embryonic mesencephalic neurons to rat pups having sustained a unilateral lesion of the nigrostriatal dopaminergic system. We examined whether, when challenged with d-amphetamine: (1) dopaminergic grafts transplanted into the previously denervated neonatal neostriatum lead to a normal activation of postsynaptic striatal neurons in term of immediate early genes activation; and (2) whether this activation is related to the action of the dopamine released from the grafts using a dopaminergic D1 antagonist. Following a mild stress-injection of saline-c-fos expression was high in the lesioned neostriatum when compared with control animals. This effect was only partially counteracted by a pre-treatment with the D1 antagonist SCH 23390, but was abolished by the graft. Administration of d-amphetamine increased c-fos expression in the neostriatum and the globus pallidus of the control group. This activation was partially blocked by the lesion. The transplant reversed the effect of the lesion and, moreover, led to a c-fos over-expression in the dorsolateral neostriatum and the globus pallidus. These overcompensations positively correlated with the abnormal rotation induced by d-amphetamine in the same animals. Pre-treatment with SCH 23390 blocked the effect of d-amphetamine on c-fos expression in control and grafted animals. Similar results were found for egr-1 but not c-jun expression. It is concluded that the neonatal lesion of the nigrostriatal dopaminergic pathway, in contrast to the adult-stage lesion, modifies the reactivity of c-fos in the neostriatum to stress, presumably in relation with compensatory reorganizations occurring following the neonatal lesion. Grafts made into neonates, when challenged with amphetamine, induce an abnormal c-fos expression which can predict the degree of overshoot observed for rotation activity. This over-expression, which depends upon the stimulation of D1 receptors, indicate an abnormal activation of postsynaptic target cells by the grafts.

Amino Acid Sequence↗