Mariann Fodor

DECUSSATIONS OF THE DESCENDING PARAVENTRICULAR PATHWAYS TO THE BRAINSTEM AND SPINAL CORD AUTONOMIC CENTERS

Decussations of descending fibers of the hypothalamic paraventricular nucleus (PVN) were investigated by using Phaseolus vulgaris‐leucoagglutinin (PHA‐L) in intact and brainstem‐operated rats. Fibers descend ipsilaterally along the brainstem and spinal cord and decussate at four levels: 1) Supramamillary decussations (SM). PVN fibers reach this area through the lateral hypothalamus and along the third ventricle in the dorsal hypothalamus. In the posterior hypothalamus some fibers crossover in the SM and terminate in the supramamillary region bilaterally. 2) Pontine tegmentum. PVN fibers run in the lateral part of the tegmentum arching to the basis of the pons. Some fibers crossover under the fourth ventricle. The locus ceruleus and the Barrington‘s nucleus receive bilateral innervation with ipsilateral dominance. 3) Commissural part of the nucleus of the solitary tract (NTS). The major crossover of PVN fibers is found here. The decussated fibers form a dense network here, and loop rostralward to innervate the entire NTS. A midsagittal knife‐cut through the NTS eliminated paraventricular‐fibers on the contralateral side. Synaptic contacts between PHA‐L‐labeled boutons and tyrozine hydroxilase‐positive neurons were verified in the NTS. The caudal ventrolateral medulla also receives bilateral innervation. 4) Lamina X of the thoracic spinal cord. Paraventricular fibers enter the lateral funiculus ipsilaterally and innervate the intermediolateral cell column (IML). Some fibers cross the midline ventral and dorsal to the central canal running to the contralateral IML, at the level of the decussation. Our results demonstrated that paraventricular projections form a continuous descending pathway on their side of origin, and provide crossover fibers which may terminate segmentally without forming long tracts after crossover. J. Comp. Neurol. 414:255–266, 1999.

Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum—Particularly the parabrachial nuclei and the locus coeruleus of the human brain

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in human parabrachial nuclei and the pontine tegmentum with immunohistochemical stainings. Brains of seven adult human subjects of 35-72 years were fixed within 2 h post mortem. Serial sections were immunostained by antisera of 14 different neuropeptides--oxytocin, vasopressin, thyrotropin-releasing hormone, angiotensin II, calcitonin gene-related peptide, beta-endorphin, dynorphin A, dynorphin B, leucine-enkephalin, alpha-melanocyte stimulating hormone, substance P, neuropeptide Y, cholecystokinin and galanin--alternately. All of these peptides were found to be present in nerve fibers and terminals, but only two, angiotensin II and dynorphin B, in cell bodies of the parabrachial nuclei. Calcitonin gene-related peptide-, neuropeptide Y-, cholecystokinin- and galanin-immunoreactive cells were present in other areas of the pontine tegmentum, like the motor trigeminal nucleus, locus coeruleus, periventricular gray matter but not in the parabrachial nuclei. Peptidergic fibers were distributed unevenly throughout the pontine tegmentum having unique, individual distribution patterns. In the parabrachial nuclei, substance P, neuropeptide Y, cholecystokinin and galanin showed the highest density of immunoreactive neuronal networks. Moderate to low concentrations of immunoreactive processes were detected by calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, dynorphin B, thyrotropin releasing hormone, leucine-enkephalin, dynorphin A, angiotensin II, beta-endorphin, vasopressin and oxytocin antisera, respectively. Other pontine tegmental areas, like the locus coeruleus, dorsal tegmental, pontine raphe and motor trigeminal nuclei as well as the central gray of the tegmental region exhibited a varying assortment of neuropeptides with distinct, individual localization patterns. Their detailed topographical distributions are mapped and given in coronal sections.

Growth hormone-releasing hormone, somatostatin, galanin and β-endorphin afferents to the hypothalamic periventricular nucleus

A combined retrograde tracing (wheat germ agglutinin-horseradish peroxidase-gold complex)-immunohistochemical technique was used to identify the origin of growth hormone-releasing hormone (GHRH)-immunoreactive (ir), beta-endorphin-ir, galanin (GAL)-ir and somatostatin (SRIH)-ir terminals in the hypothalamic periventricular nucleus, which contains all the hypophysiotrophic SRIH-ir neurons. Retrogradely labeled cells were mostly observed ipsilaterally in the arcuate, dorsomedial (DMH), suprachiasmatic nuclei and the parvocellular part of the paraventricular nucleus. They were less abundant in the ventromedial and periventricular nuclei and in the lateral hypothalamus. The proportion of retrogradely labeled GHRH cells was greater at the outer rim of the ventromedial nucleus (10%) than in the arcuate nucleus proper (3%). In the arcuate nucleus, 14% of the SRIH-ir cells projected to the periventricular nucleus. Of the GAL-ir cells in the arcuate and the DMH 10% were double-labeled. Scattered retrogradely labeled GAL-ir cells were observed in paraventricular and perifornical nuclei and in the lateral hypothalamus. Of the beta-Endorphin-ir cells in the ventral part of the arcuate nucleus 15% were retrogradely labeled. It is concluded that: (1) There is no major direct connection between the hypophysiotropic GHRH and SRIH neurons, respectively, located in the arcuate and periventricular nucleus. (2) GHRH projections to the periventricular nucleus arise mainly from cells located at the outer rim of the ventromedial nucleus. (3) Intrahypothalamic SRIH projections to the periventricular nucleus arise from arcuate SRIH neurons located along the wall of the third ventricle. (4) GAL neurons from the DMH and the arcuate nucleus innervate to the same extent the periventricular nucleus. (5) beta-Endorphin arcuate neurons strongly innervate the periventricular nucleus.

Ultrastructural localization of somatostatin- and substance P-immunoreactive nerve fibers in the feline liver

The distribution and the possible source of somatostatin- and substance P-immunoreactive nerve fibers were studied in the liver of the cat by immunocytochemical techniques. Abundant substance P-immunoreactive and a moderate number of somatostatin-immunoreactive nerve fibers were found running around the blood vessels in the perilobular connective tissue. Some somatostatin-immunoreactive nerve cell bodies were also observed in the liver. A moderate number of somatostatin-immunoreactive nerve profiles were found inside the hepatic lobules along the sinusoid endothelial cells and the hepatocytes. The interspace between the axon and hepatocyte and endothelial cells membranes was about 20 nm. Cutting the extrinsic hepatic nerves resulted in marked reduction of substance P-immunoreactive nerves but only a slight reduction of somatostatin-immunoreactive nerves in the liver. These findings provide a morphological basis for the possibility that somatostatin and substance P may act as transmitters or neuromodulators on the neighboring smooth muscle cells of vessels and may regulate the function of the hepatocytes. It is also possible that some of these fibers serve sensory function along the blood vessels.

Corticotropin-releasing factor induces differential behavioral and cardiovascular effects after intracerebroventricular and lateral hypothalamic/perifornical injections in rats.

The contribution of the lateral hypothalamic/perifornical (LH/PFx) area in mediating central effects of corticotropin-releasing factor (CRF) on cardiovascular and behavioral activity was assessed by monitoring blood pressure, heart rate and behavioral responses for a 45-min period after injections of various doses of CRF into the LH/PFx region or the lateral cerebral ventricle (intracerebroventricular, i.c.v.) in conscious, unrestrained rats in a familiar environment. After LH/PFx injection, CRF (3 and 30 ng) dose-dependently induced behavioral activation, predominantly consisting of grooming, eating and locomotor activity. Concomitantly, dose-related increases in mean arterial pressure (delta MAP) and heart rate (delta HR) were observed. Increases in MAP and HR following injection of 3 ng CRF were associated with the paroxysmal occurrence of behavioral activation and as such superimposed on CRF-induced elevation of baseline MAP and HR. Thirty nanograms CRF given i.c.v. produced grooming behavior similar to that observed after the same dose injected into the LH/PFx region, but failed to induce significant changes in cardiovascular concomitants. Rats receiving 100 ng CRF i.c.v., showed a significant increase in behavioral activity, respective to rats treated with 30 ng CRF in the LH/PFx, the tachycardiac responses, however, being similar in these groups. Both doses of CRF i.c.v. failed to induce significant delta MAP. The effects of CRF on cardiovascular and behavioral activity were more marked when the peptide was injected into the caudal part of the LH than those measured after administration into the rostral LH. Similarly, injections of CRF around or dorsal to the fornix (PFx) were more effective than those located ventrally to it. This site specificity of CRF-evoked responses was reflected in differential time response relations of the various effects. In summary, when i.c.v. is the route of administration, a higher dose of CRF is required to induce autonomic and behavioral responses similar to those elicited by CRF injected into the LH/PFx. The cardiovascular and behavioral effects of LH/PFx-CRF indicate that this region may be an important site for central CRF to produce stress-related autonomic and behavioral responses. In addition, the CRF-induced effects, both in magnitude and onset, show site specificity, the caudal LH and perifornical area being more responsive to the peptide than the rostral LH and the area ventral to the Fx. As CRF-evoked behavioral activation does not necessarily coincide with changes in MAP and HR, our data suggest a dissociation of the peptides central actions to influence behavioral and autonomic responses.

Neuropeptides in the human dorsal vagal complex: An immunohistochemical study

The distribution of twelve biologically active neuropeptides, i.e., thyrotropin-releasing hormone, corticotropin-releasing factor, pro-opiomelanocortin-derived peptides (adrenocorticotropic hormone, beta-endorphin, alpha-melanocyte-stimulating hormone), leucine-enkephalin, dynorphin A, dynorphin B, cholecystokinin, substance P, galanin and calcitonin gene-related peptide, was examined by immunohistochemistry in the human dorsal vagal complex including the nucleus of the solitary tract, the dorsal motor nucleus of the vagus and the area postrema. Immunoreactivity of all the twelve neuropeptides was found widely distributed in the various subdivisions of the nucleus of the solitary tract, showing a unique distribution for every peptide. Neuronal cell bodies immunostained with leucine-enkephalin, galanin and dynorphin B were found in this region. There were no immunopositive perikarya for any of the peptides in the other structures studied. Fibers containing galanin, corticotropin-releasing factor, substance P, dynorphin B, thyrotropin-releasing hormone and calcitonin gene-related peptide were observed at a relatively high density in the nucleus of the solitary tract. In the same structure, a moderately dense network of fibers immunostained with dynorphin A, cholecystokinin and leucine-enkephalin, but only solitary pro-opiomelanocortin-derived peptides-containing fiber fragments were observed. In the dorsal motor nucleus of the vagus the most prominent network of fibers was found to contain thyrotropin-releasing hormone, galanin and substance P. In contrast to these, no beta-endorphin immunoreactivity was detected. The area postrema contained only moderate to low densities of galanin-, substance P-, calcitonin gene-related peptide-, dynorphin B- and cholecystokinin-immunoreactive fibers.

Immunohistochemical Distribution of Neuropeptide Y and Catecholamine-Synthesizing Enzymes in Nerve Fibers of the Human Liver

The course and distribution of neuropeptide Y (NPY)-immunoreactive (ir) nerves in the human liver was studied using immunohistochemistry. The distribution and density of NPY-ir fibers was compared with tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) immunoreactivity, two enzymes which are markers for dopamine- and noradrenaline-synthetizing neurones. NPY-immunopositive nerve fibers were densely distributed in the perivascular plexus of the portal trials, along the vena centralis, as well as close to the sinusoids and hepatocytes. The distribution of perivascular TH-ir and DBH-ir nerve fibers was similar to that of NPY-ir nerves, with the exception of intralobular nerves, where close topographical relations to individual hepatocytes and sinusoids were rarely observed. These results suggest that NPY is present in noradrenergic perivascular nerve fibers; probably of sympathetic origin and also in other parasympathetic, presumably cholinergic nerve fibers around the sinusoids.

Neuropeptide Y-containing neuronal pathway from the spinal trigeminal nucleus to the pontine peribrachial region in the rat

The existence of ascending medullary neuropeptide Y (NPY)-containing projection from the spinal trigeminal nucleus to the pontine peribrachial area has been demonstrated by a combination of immunohistochemical methods with surgical transections in the lower brainstem. An NPY immunopositive cluster of varicose fibers was detected in the spinal trigeminal and in the paratrigeminal nuclei. Numerous immunoreactive perikarya could also be visualized here after colchicine treatment. Transections destroying the lateral region of the medulla oblongata resulted in an accumulation of NPY immunoreactivity in several trigeminal neurons ipsilateral to the knife cut, but no such retrograde accumulation was seen in any neuronal perikarya anywhere else in the medulla oblongata.

Dynorphin A-containing neural elements in the nucleus of the solitary tract of the rat. Light and electron microscopic immunohistochemistry

Distribution of dynorphin A (DyA) immunoreactivity in the nucleus of the solitary tract (NTS) was examined in rats after various surgical transections by light and electron microscopic immunohistochemistry. In colchicine-treated animals DyA immunostained perikarya were seen in each subdivision of the NTS. In intact rats, dense network of immunopositive nerve fibers was localized light microscopically, and synaptic contacts were found between DyA immunopositive structures (axo-axonic, axo-dendritic synapses), electron microscopically. Surgical transections medial, caudal or rostral to the nucleus did not alter the distribution pattern of DyA in the NTS. Lesion immediately lateral to the nucleus resulted in an ipsilateral appearance of immunostained cell bodies. Vagal and glossopharyngeal afferents (including baroreceptor fibers) terminate in the medial and commissural subnucleus of the NTS. Two days after extracranial vagotomy, synaptic contacts between degenerated presynaptic boutons and DyA immunopositive postsynaptic elements were observed in both medial and commissural part of the NTS. These observations provide morphological evidence suggesting that (1) axons of dynorphin A-containing cell bodies form an intrinsic network inside the nucleus; (2) these DyA cells receive direct peripheral inputs through the vagus nerve, and (3) projecting DyA neurons may exist in the NTS, they may innervate medullary, rather than forebrain, higher brainstem or spinal cord neurons.

Chapter 34: Atrial natriuretic factor in the subfornical organ and the organum vasculosum laminae terminalis

Publisher Summary The atrial natriuretic factor (ANF) has been identified as a hormone that is involved in the regulation of water and electrolyte homeostasis and blood pressure. In the brain ANF acts as a neurotransmitter, it is capable of modulating the membrane excitability of neurons. Circumventricular organs, like the subfornical organ (SFO) and the organum vasculosum laminae terminalis (OVLT) are known to participate in the central control of the salt and water balance. The SFO is outside the blood–brain barrier; it may serve as an open gate for the circulating angiotensin II and ANF. A comparison of alterations in ANF levels in the plasma and the SFO clearly shows that changes in the body fluid and electrolyte homeostasis, both in acute and chronic conditions, or in blood pressure resulted in parallel alterations in ANF levels in the plasma and in the SFO. Circulating angiotensin II influences the neuronal activity in the SFO that can be inhibited by ANF. It has been reported that ANF injected into the SFO blocks angiotensin II-induced drinking.