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D M Jacobowitz

Publications and source records attributed to D M Jacobowitz.

At least 19 recordsLinked to original sources
PubMed1979

Identification, characterization and stereotaxic mapping of intraneuronal alpha-melanocyte stimulating hormone-like immunoreactive peptides in discrete regions of the rat brain.

A highly specific antibody to alpha-melanocyte stimulating hormone (alpha-MSH) was used to histochemically localize and biochemically identify and quantitate alpha-MSH immunoreactivity in nerve fibers and cell bodies of the rat brain. alpha-MSH-like immunoreactivity was contained in fibers throughout the brain. The distribution of alpha-MSH was determined by immunocytochemistry as well as by radioimmunoassay combined with microdissection techniques. High concentrations of alpha-MSH were contained in the nucleus interstitialis stria terminalis, the median eminence and the medial preoptic, anterior hypothalamic, periventricular, paraventricular, arcuate, dorsomedial, and posterior hypothalamic nuclei. Moderate alpha-MSH concentrations were noted in the amygdala, septum, central gray, dorsal raphe, and the nucleus tractus solitarius. Cell bodies containing alpha-MSH were observed only in the arcuate nucleus. The alpha-MSH-like compound in brain had similar immunochemical and electrophoretic properties of standard alpha-MSH but high pressure liquid chromatographic analysis demonstrated that the alpha-MSH-like immunoreactivity was comprised of one major and two minor components. The major immunoreactive peak had an identical retention time as alpha-MSH and therefore may be chemically identical to alpha-MSH. The similar retention times and immunoreactivity of the other two compounds suggest a similarity in size and structure to alpha-MSH. These observations demonstrate that fibers containing alpha-MSH emanate from the arcuate nucleus to innervate many other regions of the rat brain.

Animals↗
PubMed1979

Effects of suckling on serum prolactin levels and catecholamine concentrations and turnover in discrete brain regions.

The effects of suckling on serum prolactin levels and catecholamine concentrations and turnover were examined in several discrete brain regions. Turnover rates were assessed by using the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in combination with microdissection techniques for the removal of individual brain regions and sensitive radioenzymatic assays for norepinephrine (NE) and dopaime (DA). Prolactin secretion was induced by mothers experiencing 6 h of pup removal with subsequent pup replacement. Suckling or the administration of alpha-MT to mothers resulted in a marked increase in circulating titers of prolactin. A decrease in steady-state NE concentrations in the anterior hypothalamus and a decrease in steady-state DA concentrations in the ventromedial nucleus were noted in suckled mothers. The comparison of relative rates of NE depletion after alpha-MT treatment revealed a suckling-induced increase in turnover in the ventromedial nucleus and a suckling-induced decrease in turnover in the anterior hypothalamus. Neither suckling nor alpha-MT treatment produced any changes in NE or DA turnover rates in the arcuate nucleus or median eminence. These findings demonstrate that suckling-induced activation of prolactin results in changes in noradrenergic processes in the ventromedial and anterior hypothalamic nuclei. This suggests an involvement of noradrenergic systems in suckling-induced prolactin release.

Animals↗
PubMed1979

Biochemical mapping of the noradrenergic ventral bundle projection sites: evidence for a noradrenergic--dopaminergic interaction.

Norepinephrine (NE) and dopamine (DA) concentration and dopamine turnover were measured 12 days after a unilateral or bilateral noradrenergic ventral bundle (VB) transection to determine the noradrenergic projection sites and possible interactions with dopaminergic systems. Both bilateral and unilateral VB transection resulted in a significant reduction of NE of the nucleus accumbens, lateral septal nucleus, medial forebrain bundle, ventromedial nucleus, dorsomedial nucleus and medial amygdaloid nucleus. Bilateral transection also decreased NE content of the median eminence and the periventricular and arcuate nuclei. In the medial preoptic nucleus, the nucleus interstitialis striae terminalis and the central gray catecholamine area, bilateral transection significantly decreased NE concentrations while unilateral lesions had no significant effect. The anterior hypothalamic, lateral preoptic, and paraventricular nuclei responded to bilateral VB transection with a decrease in NE concentration and to unilateral lesion with a bilateral increase in NE. In the dorsal hippocampus and the caudate nucleus, bilateral lesions had no effect on NE concentrations while unilateral transection significantly decreased NE concentrations. Regions in which neither bilateral nor unilateral VB transection produced a significant change in NE content are the olfactory tubercle, the nucleus tractus diagonalis, substantia nigra pars compacta and reticulata, ventral tegmental area, habenula, superior colliculus, and the cingulate and piriform cortices. Transection of the noradrenergic ventral bundle also produced changes in dopaminergic systems suggesting a noradrenergic--dopaminergic interaction. Bilateral VB transection decreased the dopamine concentration and turnover in the nucleus accumbens, increased steady-state levels and turnover in the nucleus tractus diagonalis and increased dopamine concentration in the lateral septum. Unilateral VB transection decreased DA concentration bilaterally in the caudate nucleus, olfactory tubercle, nucleus accumbens and the nucleus interstitialis striae terminalis but increased concentrations in the substantia nigra pars reticulata (ipsilateral) and in the ventral tegmental area (bilateral). These results indicate a broad projection field for the noradrenergic ventral bundle and suggest a noradrenergic--dopaminergic interaction.

Animals↗
PubMed1979

Neurochemical and histochemical studies of the effect of a lesion of the nucleus cuneiformis on the cholinergic innervation of discrete areas of the rat brain.

The innervation sites of the dorsal tegmental acetylcholinesterase (AChE)-containing pathway were examined in rats by combining histochemical and biochemical techniques. A lesion was placed in the nucleus cuneiformis (midbrain reticular formation) and brains were examined after 4 days survival for changes in AChE staining and choline acetyltransferase (ChAT) activity in discrete brain areas. An ipsilateral projection appears to exist to the anterior thalamic nuclei, lateral portion of the medial thalamic nucleus, parafascicular nucleus, pretectal nucleus, posterior thalamic nucleus, and deep layers of the superior colliculus. A possible bilateral innervation to the reticular nucleus of the thalamus and the dorsal and ventral lateral geniculates was found. The parallel use of AChE histochemistry and measurements of ChAT activity in discrete nuclei will be useful for future evaluation of cholinergic pathways.

Acetylcholine↗
PubMed1979

Kainic acid-induced neurotoxicity in the striatum: a histofluorescent study.

Histochemical observation of catecholamine terminals in the striatum following kainic acid injections revealed a 'sphere of influence' which contained an increased intensity of dopamine fluorescence as well as non-specific tissue destruction at the injection site. The area of involvement was approximately 50% of the striatum and varied somewhat at any one dose range depending upon the site of injection. It is suggested that destruction of regulatory neuronal systems (cholinergic, GABAergic, peptidergic, etc.) results in a net increase of dopamine in the sphere of kainic acid influence.

Animals↗
PubMed1979

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.

Animals↗
PubMed1979

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.

Animals↗
PubMed1979

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.

Animals↗
PubMed1979

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.

Animals↗
PubMed1978

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.

Animals↗
PubMed1978

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↗