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M V Sofroniew

Publications and source records attributed to M V Sofroniew.

106 records · Page 6Linked to original sources

Actions of microiontophoretically applied oxytocin, and immunohistochemical localization of oxytocin, vasopressin and neurophysin in the rat caudal medulla.

Oxytocin-, vasopressin- and neurophysin-containing axons were visualized within the rat caudal medulla using the immunoperoxidase technique. The highest densities of axons and terminals were found in the nucleus tractus solitarius, nucleus dorsalis vagus, nucleus commissuralis, nucleus reticularis lateralis and within the marginal layer of the nucleus trigeminalis. In these areas, oxytocin fibres predominated markedly over vasopressin fibres. In a series of electrophysiological experiments, neurones in these and surrounding areas were predominantly depressed following the iontophoretic application of oxytocin. This depression was seen on both spontaneous and glutamate-evoked neuronal firing.

Action Potentials↗

Projections from vasopressin, oxytocin, and neurophysin neurons to neural targets in the rat and human.

Projections from vasopressin, oxytocin, and neurophysin neurons to neural targets were examined using the immunoperoxidase method. In the rat, neural target areas were found in portions of the limbic system, diencephalon, mesencephalon, brain stem, and spinal cord. In the human, only target areas in the brain stem and spinal cord were investigated. The projections to these targets derive from hypothalamic magnocellular vasopressin or oxytocin neurons, as well as from parvocellular vasopressin neurons of the suprachiasmatic nucleus. In neural target areas, axo somatic, as well as axodendritic, contacts are made. The findings suggest that these projections interact with other neurons, rather than release hormone into the bloodstream.

Animals↗

The distribution of vasopressin-, oxytocin-, and neurophysin-producing neurons in the guinea pig brain. I. The classical hypothalamo-neurophypophyseal system.

The location, cytology and projections of vasopressin-, oxytocin-, and neurophysin-producing neurons in the guinea pig were investigated using specific antisera against vasopressin, oxytocin or neurophysin in the unlabeled antibody enzyme immunoperoxidase method. Light microscopic examination of the neurons of the supraoptic and paraventricular nuclei shows that hormone is transported not only in axons, but also in processes having the characteristics of dendrites. Neurons were found to contain only vasopressin or oxytocin; all neurons containing neurophysin appear to contain either vasopressin or oxytocin. In the neural lobe, vasopressin and oxytocin terminals are intermingled. In the median eminence, vasopressin and oxytocin fibers are intermingled in the internal zone. In a caudal portion of the median eminence, a number of vasopressin and neurophysin (but few oxytocin) axons enter the external zone from the internal zone, and surround portal capillaries. In the supraotic nucleus, vasopressin neurons outnumber oxytocin neurons with a ratio of at least 5:1. The paraventricular nucleus is separated into two distinct groups of neurons, a lateral group consisting of only vasopressin neurons, and a medial group consisting of only oxytocin neurons. In addition to axons passing to the neurohypophysis, a number of axons appear to interconnect the supraoptic and paraventricular nuclei.

Animals↗

Immunoreactive beta-endorphin and ACTH in the same neurons of the hypothalamic arcuate nucleus in the rat.

Immunoreactive ACTH and beta-endorphin (beta-End) were localized in the brain and pituitaries of normal and colchicine-treated rats, using the immunoperoxidase method at the light microscopic level. On adjacent serial 5-micron paraffin sections of anterior pituitaries, both ACTH and beta-End could be found in the same cells. On adjacent 5-micron paraffin sections of brains of colchicine-treated rats, both ACTH and beta-End could be found in the same perikarya of hypothalamic arcuate nucleus neurons. It appeared that all perikarya containing beta-End contained ACTH as well, suggesting that neurons producing beta-End also produce ACTH. Pathways of ACTH fibers corresponded to pathways of beta-End fibers. These findings suggest that the synthesis, and transport, of ACTH and beta-End are linked in the brain as well as in the pituitary, possibly through a common precursor.

Adrenocorticotropic Hormone↗

Extrahypothalamic neurophysin-containing perikarya, fiber pathways and fiber clusters in the rat brain.

Immunoreactive neurophysin (Np) is demonstrated by the immunoperoxidase technique not only within neurones of the classical hypothalamo-neurohypophyseal system, but also in extrahypothalamic perikarya and fibers. Np-positive perikarya are found in the triangular nucleus of the septum. Np fibers join the stria terminalis (ST) at the level of the anterior hypothalamus, and course medially in the ST to the central nucleus of the amygdala. Np fibers are found in the brain stem and spinal cord. Fine caliber Np fibers from the suprachiasmatic nucleus ascend to the medial dorsal thalamus and lateral septum. The presence of Np within neurones implies the presence of either vasopressin or oxytocin. Np-positive fibers in extrahypothalamic sites may interact with non-neurosecretory neurones involved in neuroendocrine regulation, or may serve as yet unknown functions.

Animals↗

Temporal patterns of vasopressin release following electrical stimulation of the amygdala and the neuroendocrine pathway in the monkey.

To evaluate a possible role of the amygdala (Amyg) in the neural control of arginine vasopressin (AVP) release, adult female monkeys (Macaca mulatta) with electrodes chronically implanted in the Amyg, hypothalamus and pituitary gland were given 5% dextrose and water infusions and were stimulated electrically at these sites. Immediately before and after, and at 5, 10, 15 and 30 min intervals following electrical stimulation, blood samples were withdrawn from unanesthetized monkeys, through implanted cardiac cannulae, for radioimmunoassay (RIA) of plasma AVP and for plasma osmolality determination. In the Amyg-stimulated monkeys, plasma AVP rose rapidly to peak values at the end of stimulation followed by an abrupt post-stimulation fall to control levels in 30 min. A small yet significant rise in plasma osmolality was also observed. Electrical stimulation of the hypothalamus and the pituitary gland yielded a temporal pattern of plasma AVP rise and fall identical to that seen following Amyg stimulation. Blood sampling, precisely timed to the onset and end of the stimulus train, was important in capturing the rise and fall in plasma AVP. Stimulus intensity determined the magnitude of plasma AVP elevation at each of these sites, with the highest current densities yielding the highest levels of plasma AVP. It is suggested that the Amyg may be involved in the neural triggering of AVP release from the neurohypophysis.

Amygdala↗

Demonstration of extrahypothalamic peptide secreting neurons. A morphologic contribution to the investigation of psychotropic effects of neurohormones.

Visualized by immunocytochemistry vasopression and neurophysin are observed in perikarya of the supraoptic and paraventricular nuclei and their fibers going to the neurohypophysis. In addition to these classical sites, vasopressin and neurophysin are located in perikarya of the organum vasculosum of the lamina terminalis and of the suprachiasmatic nuclei. Outside the hypothalamus, neurophysin-positive perikarya are found in the triangular nucleus of the septum which is a part of the limbic system. Vasopressin and neurophysin are contained in two types of extrahypothalamic fibers. Large caliber fibers are found in the amygdala, small caliber fibers in the septum and thalamus. The presence of neurosecretory perikarya and fibers outside the hypothalamus may be related to psychotropic effects of peptide hormones.

Amygdala↗

Radioimmunoassay of arginine vasopressin in Rhesus monkey plasma.

Using a new antiserum, an enzymatic radioiodination of arginine vasopressin (AVP), and the methodology of Robertson et al. (1,2), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5 muU/ml, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +/- 0.6 (SD) muU/ml and 298 +/- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +/- 0.2 muU/ml and 282 +/- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.

Animals↗

[Proceedings: Psychotropic effects of hypothalamic hormones: immunohistochemical indentification of extrahypophyseal connections of neuroendocrine neurons].

Vasopressin (VP) can be shown to exert psychotropic effects independent of its antidiuretic activity, facilitating learning and consolidation of memory in rats. Immunoreactive VP and neurophysin (NP) are localized on serial section of Bouin fixed, paraffi embedded guinea pig, rat and hamster brains. Localization was not restricted to the classical sites of supraoptic and paraventricular nucleus, medianeminence and neurohypophysis...

Animals↗

Periaqueductal grey matter stimulation produces naloxone sensitive inhibition of reticular neurones in rat caudal medulla.

Neurones in the caudal medulla reticular formation (CRF) are excited by peripheral noxious stimuli and thus may have a role in nociceptive information processing. Stimulation of sites within the dorsal periaqueductal grey matter (PAG) produced a prolonged inhibition of CRF neurones. On 11 of 16 neurones tested microiontophoretic application of naloxone was found to attenuate these inhibitions suggesting that the neurotransmitter involved may have been an endogenous opioid. Histochemical localization of beta endorphin-like immunoreactivity (beta ELI) showed fibres containing beta ELI in the vicinity of PAG stimulation sites and scattered individual fibres with short collateral branches in the vicinity of recording sites in CRF.

Analgesia↗

Can activity modulate the susceptibility of neurons to degeneration?

The provocative suggestion that maintaining an appropriate level of continuous neuronal activation, either by training or pharmacological intervention, might make neurons more robust and able to withstand degenerative insults during aging is fascinating and clearly warrants further investigation. Two cautionary points: 1) it is far from certain that Alzheimer's disease represents accelerated aging, and 2) excessive activation could be harmful to neurons in a context other than that of normally occurring "wear and tear."

Alzheimer Disease↗

Distribution of degeneration of cholinergic neurons in the septum following axotomy in different portions of the fimbria-fornix: a correlation between degree of cell loss and proximity of neuronal somata to the lesion.

The degree of cell loss of immunohistochemically stained cholinergic neurons was quantitatively compared in equivalent regions of the septum in three groups of animals with lesions transecting their axons at different levels in the fimbria-fornix (FF). Locations of different septal regions and of FF lesions were defined according to their distances from fixed anatomical reference points. Individual animals all exhibited a gradient of cholinergic cell loss, such that the severity of cell loss diminished progressively in the rostral and ventral directions as the distance from the lesion increased beyond a certain point. Comparison of animals with FF lesions in different locations showed that this gradient of cell loss shifts in the caudo-rostral and dorso-ventral directions within the septal complex in direct relation to the proximity of the axotomizing FF lesion. These findings suggest that among septal cholinergic neurons there is a fixed spatial relationship between the distance of neuronal somata from an axotomizing FF lesion and the likelihood of neuronal loss in response to axotomy. This relationship could not be defined precisely using the material studied, but simple geometrical calculations showed that within 2500 microns of the lesion cell loss is always pronounced (less than 30 per cent detectable cells vs controls) and beyond 4000 microns cell loss is generally not severe (greater than 80 per cent detectable cells). Between these two distances cell loss diminishes in a gradiated manner. Thus, relatively small differences (1 mm) in the location of FF lesions can lead to marked differences in the severity of degeneration observed in certain equivalent regions of the septum. The findings have implications both for attempts to understand the causes underlying retrograde neuronal degeneration and for studies investigating means of preventing retrograde degeneration of cholinergic septal neurons.

Animals↗