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Biomedical subjects

D M Jacobowitz

Publications and source records attributed to D M Jacobowitz.

At least 181 records · Page 10Linked to original sources
PubMed1983

Effects of time and experience on hippocampal neurochemistry after damage to the CA3 subfield.

Bilateral injections of kainic acid into the hippocampal CA3 subfield destroyed the CA 3 pyramidal cells and produced a behavioral impairment, an inability to solve spatial maze problems. The behavior recovered, however, with daily experience in a maze task, and the rate of recovery was accelerated by additional daily experience. This recovery of function could be the result of compensatory changes in the distribution or function of the various hippocampal pathways. In the present experiment, this possibility was investigated neurochemically. Five putative neurotransmitters or their synthetic enzymes were measured in dissected regions of the hippocampal formation. Both the long-term effects of the lesions and the effects of behavioral training were determined. A number of alterations in hippocampal neurochemical systems were detected. Acute changes due to the lesions included a widespread loss of glutamate, and regionally specific decreases in glutamic acid decarboxylase (GAD) activity and cholecystokinin (CCK) and norepinephrine (NE) concentrations. Long-term changes included a decline in choline acetyltransferase (ChAT) activity throughout the hippocampal formation, and increases in NE in certain regions. Behavioral testing prevented the decline of ChAT activity, and increased the concentrations of GAD and CCK. The neurochemical conditions present at the time when trained rats recovered behavioral function may indicate the crucial conditions for the occurrence of the behavior.

Animals↗
PubMed1983

Application of high-performance liquid chromatography with electrochemical detection to the determination of catecholamines in microdissected regions of the rat brain.

High-pressure liquid chromatography (HPLC) with electrochemical detection was applied for measurement of catecholamines in microdissected tissues from discrete brain regions. Brain areas were dissected, extracted and processed for HPLC assay without further purification. The advantage of this method is its simplicity and relatively low cost and may therefore be applied to the measurement of amines in brain micropunches.

Animals↗
PubMed1983

Lesions of the paraventricular nucleus area of the hypothalamus disrupt the suprachiasmatic leads to spinal cord circuit in the melatonin rhythm generating system.

The circadian rhythm in melatonin production in mammals is regulated by a suprachiasmatic (SCN) leads to spinal cord leads to pineal circuit. In the present investigation the possible participation of the paraventricular nucleus of the hypothalamus (PVN) in the SCN leads to spinal cord segment of this circuit was investigated in the rat. Bilateral lesions of the PVN area were produced and one to two weeks later melatonin production was evaluated by measuring the activities of the two pineal enzymes required for the formation of melatonin from serotonin, indoleamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), and urinary 6-hydroxymelatonin, the major melatonin metabolite. In some cases pineal melatonin was also measured. Control animals received sham-PVN lesions. Histological examination of the lesions indicated that the PVN were bilaterally destroyed 100% in 12 animals. The nighttime pineal melatonin and urinary 6-hydroxymelatonin values in this group were reduced about 90%, nighttime pineal NAT activity was reduced about 98%, and HIOMT activity about 75%. The urinary 6-hydroxymelatonin values of PVN-lesioned animals and animals with denervated pineal glands were similar. In animals with hypothalamic lesions involving less than 30% of the PVN, nighttime values of NAT, HIOMT, and urinary 6-hydroxymelatonin were normal; in animals with 30 to 95% PVN damage these parameters were altered to a small degree. These studies, together with histochemical observations, indicate the SCN neurons responsible for pineal circadian rhythms project to the PVN area of the hypothalamus.

Acetylserotonin O-Methyltransferase↗
PubMed1983

Cholinergic projection sites of the nucleus of tractus diagonalis.

The cholinergic projection sites of the basal portion of the nucleus of the tractus diagonalis (td) were studied following bilateral stereotaxic lesions. Choline acetyltransferase (ChAT) activity was measured in various cortices, hippocampus and amygdala. Significant decreases in ChAT activity were observed in the anterior and posterior cingulate cortex, the frontal cortex, occipital cortex, hippocampus and dentate gyrus. It is concluded that (1) the hippocampus is innervated by the basal portion of the td and not from the medial septal nucleus, (2) the td contains cholinergic cell bodies which project widely to the cortex and hippocampus. It is suggested that these cholinergic projections have important influences on emotional behavior via connections with the cortex and limbic system.

Acetylcholine↗
PubMed1983

Bovine pancreatic polypeptide-like immunoreactive nerves in the rat major cerebral arteries.

Immunofluorescence histochemical observation of the major cerebral arteries of the rat demonstrated the presence of an extensive plexus of bovine pancreatic polypeptide (BPP) containing nerves. The density of the nerves were similar to those previously observed in the adrenergic plexus. The density of BPP-immunoreactive fibers markedly decreased following bilateral superior cervical ganglionectomy. It is concluded that BPP-containing fibers of the cerebral arteries emanate mostly from the superior cervical ganglion and that BPP and norepinephrine coexist in the adrenergic nerves.

Animals↗
PubMed1983

Choline acetyltransferase activity in the nucleus tractus solitarius: regulation by the afferent vagus nerve.

The influence of nodose ganglionectomy or transection of the peripheral branches of the afferent vagus nerve on choline acetyltransferase (ChAT) activity in the nucleus tractus solitarius (NTS) was studied. ChAT activity was reduced in the microdissected caudal and intermediate portions of the NTS in vagotomized as well as ganglionectomized rats. However, only the ganglionectomy resulted in the degeneration of medullary nerve fibers. These results suggest that the changes in ChAT activity in the NTS are independent of neuronal degeneration and may be due to transynaptic modulation of ChAT activity by afferent vagal impulses. The presence of ChAT in the sensory nodose projection to the NTS, however, cannot be ruled out.

Animals↗
PubMed1983

A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1983

Sex differences in specific proteins in the preoptic medial nucleus of the rat hypothalamus.

Using two-dimensional gel electrophoresis and a highly sensitive silver stain, specific proteins in adult male and female rat brain were examined. Based on previous studies, the preoptic medial nucleus (POM) of the hypothalamus served as the area of interest, with the parietal cortex acting as control. A significant difference between the sexes was found in the concentration of two proteins in the POM, a difference which was not found in the parietal cortex.

Animals↗
PubMed1983

Vasoactive intestinal peptide inhibitory innervation in bovine mesenteric lymphatics. A histochemical and pharmacological study.

The localization of vasoactive intestinal peptide-immunoreactive nerves innervating bovine lymphatic vessels was studied by an immunohistochemical technique. Nerve fibers containing vasoactive intestinal peptide immunoreactivity were present in the smooth muscle layers as well as in the adventitia of all mesenteric lymphatics that were examined. The effect of vasoactive intestinal peptide on isolated lymphatic vessels in vitro was studied. Vasoactive intestinal peptide caused a concentration-dependent relaxation of bradykinin-induced contractions of lymphatic vessels. The threshold and maximum relaxations were achieved with vasoactive intestinal peptide at concentrations less than 6 X 10(-9) M and 3 X 10(-7) M, respectively. The relaxant response to vasoactive intestinal peptide was not modified by atropine, propranolol, bretylium, or tetrodotoxin. These results suggest that vasoactive intestinal peptide may be a possible inhibitory neurotransmitter that causes relaxation of lymphatic vessels.

Animals↗
PubMed1983

Mapping and quantitation of proteins from discrete nuclei and other areas of the rat brain by two-dimensional gel electrophoresis.

A map of the location and relative concentration of a number of different proteins present in 25 distinct neuroanatomical regions of the male rat brain has been established utilizing two-dimensional polyacrylamide gel electrophoresis. The regions examined include cortical areas as well as nuclei from the hypothalamus, amygdala, thalamus, forebrain, and hindbrain. Tissue samples were obtained from each region of interest by microdissection. Proteins within these samples were first separated by charge using the technique of isoelectric focusing. In the second dimension, proteins were separated by mass on polyacrylamide slab gels containing sodium dodecyl sulfate. Proteins were visualized using a highly sensitive silver stain and quantitated by computerized scanning densitometry. The results demonstrate that all proteins examined varied somewhat in concentration among the different brain regions. The majority (53%) of polypeptides selected for quantitation were found to vary less than 4-fold in concentration between the neuroanatomical areas with the lowest and highest detected amounts. In contrast, approximately 10% of the proteins examined varied widely in the quantity measured in each brain region, with concentration values ranging more than 10-fold between the regions with the lowest and highest detected amounts. This atlas is a first attempt at systematically classifying the mass, charge, and relative concentration of proteins present in a variety of regions of the rat brain. The system presented here will serve as a basis for future studies in this area.

Animals↗
PubMed1982

Catecholamines and vasopressin in hindbrain nuclei of hypertension prone and resistant rats.

Norepinephrine and epinephrine concentrations in the caudal and rostral part of the nucleus tractus solitarii (NTS) and in locus coeruleus (LC) of Sabra hypertension prone (SBH) rats are 2-4-fold higher than in the parent Sabra (SB) strain; SB rats have higher concentrations than the Sabra hypertension resistant (SBN) rats. Dopamine concentrations were higher in SBH as compared to SB and SBN rats only in the caudal NTS. Vasopressin concentrations in the NTS of SBH were 3-fold higher than the levels found in SB or SBN rats. These data suggest that catecholamines and vasopressin in specific brainstem nuclei are involved in either the pathogenesis or central response to hypertension in SBH rats.

Animals↗
PubMed1982

N-acetylation regulates the behavioral activity of alpha-melanotropin in a multineurotransmitter neuron.

A multineurotransmitter neuronal system that synthesizes and secretes both acetylated and deacetylated forms of alpha-melantropin and beta-endorphin is present in rat and human brain. The N-acetylated from of alpha-melanotropin had more potent behavioral effects than the deacetylated alpha-melanotropin. In the case of beta-endorphin, however, the deacetylated form has been shown to be more potent than the acetylated form. Enzymatic N-acetylation appears to be an important regulatory process for modulating the behavioral activity of peptides secreted from the opiomelanotropinergic multineurotransmitter neuron.

Acetylation↗
PubMed1982

Hypothalamic sites for cardiovascular and sympathetic modulation by prostaglandin E2.

Prostaglandin E2 (PGE2, 0.5 - 5 nmol/kg) injected into the lateral cerebral ventricle of the rat increased the systemic blood pressure and heart rate in a dose dependent manner. These effects were accompanied by increases in plasma norepinephrine and epinephrine concentration. Injection of low dose of prostaglandin E2 into discrete hypothalamic nuclei induced a marked increase in heart rate, a moderate increase in the arterial blood pressure and a significant elevation of plasma norepinephrine level. This study suggests a possible central role for PGE2 in modulation of cardiovascular dynamics and sympathetic nervous activity.

Animals↗
PubMed1982

Selective chemical hepatic sympathectomy in the dog.

Intraportal injection of 6-hydroxydopamine (6-OHDA) was used to produce selective hepatic sympathectomy in the dog. Previously reported techniques for 6-OHDA induced hepatic sympathectomy in rats and cats were modified considerably using alpha and beta adrenergic blocking agents to prevent the otherwise intense and fatal sympathomimetic response which has prevented adaptation of the intraportal 6-OHDA injection for dogs. After 6-OHDA injection, histofluorescent staining demonstrated loss of hepatic adrenergic nerves with preservation of normal adrenergic innervation in the heart and pancreas. Tyramine iv was used to further document functional integrity of peripheral sympathetic mechanisms. This technique provides a useful model for evaluation of sympathetic nervous system mediated changes in hepatic metabolic function associated with the neuroendocrine response to hemorrhage in the classic dog model.

Animals↗
PubMed1982

Mechanisms involved in central cardiovascular effects of prostaglandin F2 alpha.

Prostaglandin F2 alpha (PGF2 alpha) injected into the cerebroventricular system (icv) of halothane-anesthetized rats increased the arterial blood pressure, heart rate, and rectal temperature. These effects were accompanied by a preferential increase in plasma norepinephrine concentration. Plasma levels of epinephrine, renin, and vasopressin were not changed in the PGF2 alpha-icv-treated rats. Bilateral vagotomy did not affect the PGF2 alpha-induced hypertension and tachycardia nor was there any change in the selective increase in plasma norepinephrine concentration. Hexamethonium pretreatment suppressed, in a dose-response manner, the increases in blood pressure, heart rate, and rectal temperature in response to PGF2 alpha-icv. Plasma norepinephrine and epinephrine levels were not altered by PGF2 alpha-icv in hexamethonium-treated rats, but plasma vasopressin concentration was markedly elevated in all hexamethonium-infused rats. These results suggest that selective central activation of the sympathetic nervous system underlies the profound cardiovascular and temperature responses elicited by central administration of PGF2 alpha.

Animals↗