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D M Jacobowitz

Publications and source records attributed to D M Jacobowitz.

At least 235 records · Page 13Linked to original sources

Specific uptake and retrograde flow of antibody to dopamine-beta-hydroxylase by central nervous system noradrenergic neurons in vivo.

This study sought to determine whether the administration in vivo of antibody to dopamine-beta-hydroxylase (AD beta H) is taken up by central noradrenergic neurons and transported by retrograde flow to the cell bodies of origin. AD beta H serum or preimmune serum (control) in volumes of 1--20 microliter were stereotaxically injected into the lateral ventricle. Rats were sacrificed at times ranging from 1 h to 8 days. Cryostat sections were stained with fluorescein conjugated IgG. After 24 h, a bilateral granular fluorescence was seen only in neuronal cell bodies corresponding to noradrenergic cell groups A1--A7 with the most intense fluorescence localized within perikarya and processes of the locus coeruleus (A6) and subcoeruleus. This technique also permitted the visualization of the ascending dorsal and ventral noradrenergic bundles as well as varicose fibers and terminals in a pattern identical to that reported with histofluorescence, autoradiographic, biochemical and classical immunofluorescence techniques for the identification of noradrenergic fiber distributions. At 3 and 6 h, the first detectable fluorescence was observed in forebrain noradrenergic terminals and in fibers of the dorsal and ventral noradrenergic bundles. At 10 h fluorescent varicosities were first visualized within the caudal dorsal bundle and some cytoplasmic fluorescent particles were seen within locus coeruleus cell bodies. After 18 h locus coeruleus and subcoeruleus cell bodies were heavily stained, whereas medullary noradrenergic cell groups and nerve fibers were not labeled until after 24 h. An intense locus coeruleus fluorescence remained for 3 days and was completely absent after 6 days. Bilateral transection of the dorsal noradrenergic bundle in the rostral mesencephalon, at the time of injection, effectively blocked the retrograde transport of fluorescing material to the locus coeruleus. The overall staining pattern suggests that, in vivo, central noradrenergic fibers are capable of taking up antibody to dopamine-beta-hydroxylase. The ability of a dorsal bundle transection to abolish locus coeruleus staining, as well as the time course of AD beta H staining in noradrenergic neurons, suggests that AD beta H is transported via a rapid retrograde flow process. This technique combines retrograde transport of a marker protein with the sensitivity and specificity of immunocytochemical procedures to provide a new tool for the neuroanatomical study of neurotransmitter systems.

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Potential noradrenergic regulation of serotonergic neurons in the median raphe nucleus.

Pharmacological and morphological evidence suggests that the functional activity of serotonergic neurons may be regulated by catecholamines. We have attempted to reveal a potential pathway by which this interaction might occur. Rats received bilateral knife cut lesions of the ventral noradrenergic bundle which severed the A-1 and A-2 cell body contributions to this projection. Controls received a sham lesion into the cerebellum. Two weeks later all animals were sacrificed, and norepinephrine and serotonin levels were measured in discrete nuclei of the brain. Lesion placement was confirmed histofluorometrically. Serotonin levels in the median raphe nucleus were significantly reduced by 40%, but levels of serotonin were unaffected in the dorsal raphe nucleus and 8 serotonergic terminal regions. The lesions did not affect levels of norepinephrine in the locus coeruleus, cingulate cortex, or habenula. This study suggests that a noradrenergic projection to the median raphe nucleus from the A-1 and A-2 cell body groups may modulate serotonergic neuronal function.

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Effect of hypophysectomy on alpha-melanotropin in discrete regions of the rat brain.

The effect of hypophysectomy on alpha-melanotropin (alpha MSH) concentrations in discrete brain regions was investigated. Hypophysectomy resulted in a 38-69% decrease in alpha MSH concentration in alpha MSH terminal regions 4 weeks after surgery. In contrast, the alpha MSH concentration in the arcuate nucleus, site of alpha MSH containing perikary, was unaffected by hypophysectomy. These results indicate that the brain alpha MSH system is distinct from, but related to that of the pituitary.

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A diurnal rhythm of immunoreactive alpha-melanocyte-stimulating hormone in discrete regions of the rat brain.

A significant diurnal variation in alpha-melanocyte stimulating hormone (alpha-MSH) concentrations was observed in discrete regions of the rat brain. During the 12 h light: 12 h dark cycle, alpha-MSH concentrations in each case were highest during the light period and lowest during the dark period. At 09.00 h, 3 h after lights were turned on, the peak alpha-MSH concentration occurred in the median eminence, the arcuate and dorsomedial hypothalamic nuclei and the periventricular thalamic nucleus. The paraventricular and anterior hypothalamic nuclei had highest alpha-MSH concentrations at 13.00 h. In the medial preoptic nucleus, the peak alpha-MSH concentrations appeared at 17.00 h. These changes in alpha-MSH content may reflect an alpha-MSH role in circadian variations in behavioral and neuroendocrine processes.

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Effects of estrogen and progesterone on plasma gonadotropins and on catecholamine levels and turnover in discrete brain regions of ovariectomized rats.

Estradiol benzoate (EB) was administered, either alone or followed 48 h later by progesterone to ovariectomized rats. Plasma gonadotropins (FSH and LH) and steady state levels of norepinephrine (NE) and dopamine (DA) in 17 individual brain nuclei were assayed. In addition, catecholamines were measured after administration of the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in order to assess hormonal influences on turnover. Treatment with EB, which lowered plasma FSH and LH, reduced the depletion of NE produced by alpha-MT in the lateral septum, interstitial nucleus of the stria terminalis, and central gray catecholamine area, and reduced the depletion of DA in the nucleus of the tractus diagonalis. EB enhanced NE depletion in the periventricular and anterior hypothalamic nuclei, and raised steady state levels of NE in the medial amygdaloid nucleus. These effects were reversed by subsequent treatment with progesterone, which stimulated FSH and LH release. EB plus progesterone enhanced the alpha-MT-induced depletion of NE over that observed with EB alone in the arcuate nucleus, and similarly enhanced DA depletion in the interstitial nucleus of the stria terminalis. EB plus progesterone prevented the depletion of NE by alpha-MT in the paraventricular and ventromedial nuclei, and also lowered resting NE levels in the paraventricular nucleus. The results suggest that catecholamine neurons in several discrete brain regions participate in the stimulatory and inhibitory feedback effects of ovarian hormones on gonadotropin secretion, and perhaps also on the hormonal induction of sexual receptivity.

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A mapping of the distribution of acetycholine, choline acetyltransferase and acetylcholinesterase in discrete areas of rat brain.

Acetylcholine (ACh) concentration, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in 60 discrete areas dissected from the rat forebrain. All 3 substances were detectable in every region examined. The range for ACh levels was approximately 9-fold, with highest levels in the striatal and mesolimbic areas. Wider ranges were found for ChAT and AChE. In addition to not having a uniform distribution ACh, ChAT and AChE did not always show proportional variations. ACh levels did not appear to relate to the activity of either enzyme in a simple manner. There was a better correlation (r = 0.902) between the activities of ChAT and AChE, with AChE activities always being higher. In some regions, AChE was disproportionately low or high relative to ChAT. In general, the biochemical results presented here are compatible with histochemical studies of AChE. Such measurements in small brain regions should prove valuable in future experiments designed to determine cholinergic function and localize cholinergic pathways.

Acetylcholine↗

Changes in catecholamine content in discrete brain nuclei during the estrous cycle of the rat.

Norepinephrine (NE) and dopomine (DA) concentrations were measured in discrete brain nuclei in female rats at different stages of the 4-day estrous cycle. In the medial preoptic and paraventricular nuclei, NE levels were reduced on the days of proestrus and estrus as compared to metestrus-diestrus. NE levels sharply increased between estrus and metestrus in the lateral septal nucleus but did not vary significantly at other times. In the mesencephalic central gray catecholamine area, NE levels were elevated on metestrus as compared to all other days of the cycle. DA concentrations also varied in certain nuclei during the estrous cycle. In the lateral septum, DA levels were highest during diestrus, and in the nucleus of the tractus diagonalis, DA levels were highest on metestrus. The DA concentration of the caudate nucleus decreased between proestrus and estrus and remained low through metestrus. DA in the medial preoptic nucleus showed a similar pattern of change as did NE. In the median eminence DA levels increased significantly from proestrus afternoon to estrus, but did not vary on the other days. It is concluded that cyclic activity of catecholamines in a few discrete areas of the brain may be related to the fluctuations of the gonadotropins and ovarian hormones to influence ovulation and mating behavior.

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A brainstem atlas of catecholaminergic neurons and serotonergic perikarya in a pygmy primate (Cebuella pygmaea).

The present paper provides a brainstem atlas showing the distribution of catecholaminergic cells and processes, as well as serotonergic perikarya, in the pygmy marmoset. The findings revealed by the Falck and Hillarp histofluorescence method conform in essential details to what has been described in rodents. These and other comparative data indicate that a prototypical pattern of organization of aminergic systems has been retained in the evolution of primates.

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Catecholamines in discrete areas of the hypothalamus of obese and castrated male rats.

Levels of norepinephrine (NE) and dopamine (DA) were measured in eight discrete regions of the hypothalamus in three groups of male rats; genetically obese (fafa), non-obese (FaFa) and castrated non-obese (FaFa). DA levels showed no significant differences among the groups in any of the regions. NE levels in the paraventricular nucleus (PVN) were significantly lower in the obese and castrated animals than in the normal animals. In the median eminence (ME), NE levels were significantly decreased for the castrated group. None of the other regions sampled showed significant differences in NE levels.

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Method for the rapid determination of norepinephrine, dopamine, and serotonin in the same brain region.

A method is presented for the fluorometric analysis of norepinephrine dopamine and serotonin. This procedure is a combination of an unpublished catecholamine assay developed by Hogans and of the o-phthaldialdehyde serotonin reaction reported by Maickel and Miller [9]. This procedure should greatly facilitate the correlation of neurotransmitter levels in brain regions with changes in behavior produced by experimental manipulations.

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