PubMed Health⌕ Search

Biomedical subjects

D M Jacobowitz

Publications and source records attributed to D M Jacobowitz.

At least 217 records · Page 12Linked to original sources

Changes in central cholinergic neurons in the spontaneously hypertensive rat.

The activity of choline acetyltransferase (ChAT) was measured in discrete areas of the brain in 4-, 8- and 12-week-old spontaneously hypertensive rats (SH rats) and age matched Wistar Kyoto (WKY rats) controls. The concentration of acetylcholine (ACh) was also measured in certain hindbrain nuclei of 12 week SH and WKY rats. An increase in the ChAT activity and ACh concentration in the locus coeruleus was detected in 12-week-old SH rats. Decreases in the ChAT activity were found in several hypothalamic nuclei of SH rats, specifically in the paraventricular nucleus of 4-week-old rats, in the dorsomedial nucleus at 8 and 12 weeks and in the posterior hypothalamic nucleus at 12 weeks. Changes in ChAT activity were also detected in 4- and 8-week-old SH rats in the anterior ventral thalamus and in the nucleus gigantocellularis. These results suggest that cholinergic nerve activity in certain rat brain areas, several of which play a role in cardiovascular control, is altered in spontaneously hypertensive rats.

Acetylcholine↗

Effects of food restriction on the periodicity of corticosteroids in plasma and on monoamine concentrations in discrete brain nuclei.

The concentrations of plasma corticosteroids and of norepinephrine, dopamine and serotonin in microdissected brain regions were measured at 08.00, 12.00 and 20.00 h in male rats fed ad libitum and in rats whose food intake was restricted to 09.30-11.30 h. In ad libitum fed animals, plasma corticosteroids were lowest at 08.00 and highest at 20.00 h. As demonstrated previously, restriction of food availability was associated with appearance of a peak in corticosteroids at 08.00 h. In ad libitum fed animals, serotonin and dopamine concentrations in the median eminence were higher at 20.00 than at 08.00 h. Restriction of food availability significantly decreased the levels of these neurotransmitters at 20.00 h. In the paraventricular nucleus, amygdala, and hippocampus of ad libitum fed animals, serotonin levels were lower at 20.00 than at 08.00 or 12.00 h. In food-shifted animals, this pattern was reversed so that lowest levels of serotonin occured at 08.00 and markedly elevated levels were observed at 12.00 and 20.00 h. No changes were noted in norepinephrine content of the median eminence or paraventricular nucleus of ad libitum fed or food restricted animals. These results indicate that the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regime is accompanied by changes in the periodicity of neurotransmitter concentrations in specific regions of the brain, and that such patterns are dissimilar in different regions.

Adrenal Cortex Hormones↗

Demonstration of an endogenous circadian rhythm of alpha-melanocyte stimulating hormone in the rat pineal gland.

alpha-Melanocyte stimulating hormone (alpha-MSH) has been identified and characterized in the rat pineal gland by a combination of immunochemical and high pressure liquid chromatographic techniques. The immunoreactivity in pineal extracts was separated into two chromatographic components. The major component had a retention time identical to that of alpha-MSH while the minor component eluted just slightly before standard alpha-MSH. Male rats maintained in a 12 h photoperiod demonstrated a marked circadian rhythm in pineal alpha-MSH concentration. Concentrations that peaked at 07.00 h, 1 h after the lights were turned on, were greater than 5 times the nadir which occurred at 01.000 h. Animals house in chronic dark for 7 days maintained the diurnal variation of alpha-MSH concentrations. However, in chronically dark housed rats, the peak shifted to 05.000 h and was greater than 10 times the nidir of this rhythm and approximately 4 time the peak at 07.00 in alternating light/dark conditions. Rats exposed to chronic light for 7 days maintained a pineal alpha-MSH rhythm although the amplitude of the peak was significantly decreased compared to the rhythm in animals housed in alternating light/dark conditions. Neither hypophysectomy nor superior cervical ganglionectomy had any effect on the alpha-MSH rhythm. Lesion of the arcuate nucleus, the major source of alpha-MSH-containing nerves in the brain, did not significantly affect pineal alpha-MSH concentrations. These data demonstrate a circadian alpha-MSH rhythm in the rat pineal and suggest an alpha-MSH involvement in the rhythmic processes of the pineal gland.

Animals↗

Bovine parathyroid catecholamines: a chemical and histochemical study.

Bovine parathyroid glands contain large amounts of dopamine (3.4-13.9 pg/microgram), but very little norepinephrine. Fluorescent histochemistry demonstrates only rare adrenergic nerve terminals on vasculature. Single dopamine-containing cells, most likely mast cells, are scattered in large numbers throughout the connective tissue stroma.

Animals↗

Demonstration of substance P in aortic nerve afferent fibers by combined use of fluorescent retrograde neuronal labeling and immunocytochemistry.

Combined use of the intraaxonal retrograde transport of the fluorescent marker 'true blue' with substance P (SP) immunocytochemistry has been used to trace the nodose ganglion projections of SP-containing neurons of the aortic depressor nerve. It has been found that (1) SP immunoreactive (SP-I) cell bodies are clearly demonstrable in clusters in the rostral part of the nodose ganglion without the aid of colchicine pretreatment; (2) 'true blue' is retrogradely transported to the nodose ganglion following its application to the central cut end of the aortic nerve; (3) 'true blue' fluorescence and SP fluorescent immunoreactivity can be visualized in the same tissue section and certain cell bodies in the nodose ganglia contain both SP-I and retrogradely transported 'true blue'. These results indicate that the aortic nerve which projects from the aortic arch baro- and/or chemoreceptors to brainstem vasomotor centers contains SP-I afferent fibers which emanate form the nodose ganglion.

Afferent Pathways↗

Substance P as a baro- and chemoreceptor afferent neurotransmitter: immunocytochemical and neurochemical evidence in the rat.

The possibility that substances P (SP) is a neurotransmitter of baro- and chemoreceptor afferents in the rat was investigated. SP-like immunoreactivity (SP-I) was analyzed quantitatively by radioimmunoassay in various levels of the nucleus tractus solitarius (NTS), the site of termination of these afferents while SP-containing afferent neurons were studied in various portions of the peripheral pathways by immunocytochemistry. It was found that the NTS contained significant amounts of SP-I and that unilateral removal of the nodose ganglia reduces the SP-I content of those portions of the NTS known to receive vagal afferents. In addition, SP-I was visualized in discrete fibers in the tunica adventitia of the aortic arch and carotid sinus regions, the vagus nerve and nodose ganglia. These results in the rat are consistent with our previous studies in the cat and provide further evidence that SP is contained within baro- and chemoreceptor afferent nerves.

Afferent Pathways↗

Studies of alpha-MSH-containing nerves in the brain.

alpha-Melanocyte stimulating hormone (alpha-MSH) immunofluorescence was observed in the rat brain using a highly specific and well-characterized antibody. alpha-MSH was contained in the arcuate nucleus cell bodies and in varicose fibers distributed throughout the brain stem. alpha-MSH-containing fibers were present in various nuclei of the hypothalamus, preoptic area, septum, amygdala, mammillary body and central gray area. The distribution of alpha-MSH was verified by radioimmunoassay following microdissection of discrete brain nuclei. High concentrations of alpha-MSH were contained in the median eminence, medial preoptic, anterior hypothalamic, periventricular, paraventricular, arcuate, dorsomedial, posterior hypothalamic nuclei and bed nucleus of the stria terminalis. Moderate alpha-MSH concentrations were noted in the amygdala, septal area, central gray, dorsal raphe, and the nucleus tractus solitarius. Hypophysectomy did not significantly reduce the quantity of alpha-MSH fibers in the brain, thereby suggesting an extra-pituitary source of alpha-MSH. Lesions of the arcuate nucleus did, however, completely abolish alpha-MSH-like immunoreactivity. The alpha-MSH-like compound in the brain has immunochemical and electrophoretic properties similar to those of standard alpha-MSH. High pressure liquid chromatographic analysis demonstrated that the alpha-MSH immunoreactivity in the brain was comprised of one major component having a retention time identical with that of standard alpha-MSH, as well as 2 minor components. In male rats kept on a 12-h light-dark schedule (0600-1800 hours), there was a diurnal rhythm of alpha-MSH in the hypothalamic nuclei with peak content at 0900 in the arcuate and periventricular nuclei of the thalamus; at 1300 in the dorsomedial, paraventricular and anterior hypothalamic nuclei, and at 1700 in the medial preoptic nucleus. In the pineal gland a diurnal rhythm was also observed with a peak concentration at 1900. Six days of constant light, however, abolished the morning rise in alpha-MSH. Rats kept in constant dark for 6 days showed a marked increase in the alpha-MSH peak (12-fold) occurring at 0500. Normal diurnal rhythm of alpha-MSH was still observed in hypophysectomized rats. It is suggested that alpha-MSH may function as a neurotransmitter or as a neuromodulator in the brain. The extensive distribution of alpha-MSH in the brain suggests that it is involved in significant neuronal circuitry and supports the notion of a neuroregulatory role for this neuropeptide. This lays the groundwork for a rational approach to further study of possible interactions between alpha-MSH and other neuronal systems.

Animals↗

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↗

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↗

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↗

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↗

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↗