Biomedical subjects

F E Bloom

Publications and source records attributed to F E Bloom.

At least 235 records · Page 13Linked to original sources

PubMed1983

Double immunostaining reveals distinctions among opioid peptidergic neurons in the medial basal hypothalamus.

We adapted an uncommon peroxidase substrate, ortho-dianisidine, to double immunostaining methodology in order to analyze the degree of neuronal coexistence of pro-opiomelanocortin-derived peptides and to compare the distribution of neurons containing beta-endorphin immunoreactivity (ir) with those containing enkephalin-ir and dynorphin-ir in the medial basal hypothalamus. Double immunostaining demonstrated co-localization of beta-endorphin-ir, adrenocorticotropic hormone-ir, and gamma 3-melanocyte stimulating hormone-ir in medial basal hypothalamus (MBH) neurons. However, while all perikarya containing beta-endorphin-ir invariably contained adrenocorticotropic hormone-ir, not all of these cell bodies contained gamma 3-melanocyte stimulating hormone-ir. In contrast, separate neuronal cell bodies containing beta-endorphin-ir, enkephalin-ir, and dynorphin-ir were distributed throughout the rostral-caudal extent of the MBH. Fibers containing enkephalin-ir closely surrounded cell bodies containing beta-endorphin-ir, suggesting axosomatic contacts between these two opioid peptidergic neuronal populations.

Adrenocorticotropic Hormone↗

PubMed1983

Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats.

Corticotropin releasing factor (CRF) is a 41-residue peptide, capable of stimulating the secretion of corticotropin (ACTH)-like and beta-endorphin-like immunoreactivity from the adenohypophysis. Low doses of CRF (0.0015-0.15 nM) given intracerebroventricularly (i.c.v.) produced changes in electrographic activity suggestive of increased arousal. Higher doses of CRF (1.5-3.75 nM) induced, over a period of 3-7 h, electrographic and behavioral signs of seizure activity indistinguishable from those which occur following electrical 'kindling' of the amygdala.

Animals↗

PubMed1983

Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer's type.

Serial sections of human brainstem were used to determine the total number of pigmented cells in locus coeruleus and, by immunohistochemical staining using an antiserum directed against human dopamine-beta-hydroxylase (DBH), the number of DBH-positive cells. In 12 brains from elderly control and dementia subjects there wer not significant differences in the total cell populations determined in the same brain by the two techniques. In 6 patients with senile dementia of Alzheimer's type there was a variable loss (average about 60% reduction) in locus coeruleus cells when compared to controls of similar age. The loss of noradrenergic neurones from locus coeruleus was accompanied by an average reduction of similar magnitude in noradrenaline concentration in temporal cortex, with no change or an increase in dopamine content. There was also a significant reduction in the cholinergic marker choline acetyltransferase in cortex samples from the dementia cases.

Aged↗

PubMed1983

A combined vascular-catecholamine fluorescence method reveals the relative vascularity of rat locus coeruleus and the paraventricular and supraoptic nuclei of the hypothalamus.

Vascular perfusion with a fluorescent dye, Pontamine sky blue, was combined with glyoxylic acid-induced catecholamine fluorescence to produce simultaneous staining of intracerebral blood vessels and catecholamine-containing cells and fibers. Quantitative measurements of blood vessels per unit area revealed that the vascular density of rat locus coeruleus did not differ from the surrounding neuropil but was significantly lower than that of the hypothalamic supraoptic and paraventricular (PVN) nuclei. Moreover, the density of blood vessels in the magnocellular portion of PVN was not uniform throughout its rostrocaudal extent but was dense only in a specific subdivision of lateral PVN, which is predominantly vasopressinergic and is also heavily innervated by catecholamine terminals.

Animals↗

PubMed1983

Immunohistochemical distribution of pro-somatostatin-related peptides in cerebral cortex.

Mammalian brain contains 3 peptides related to the pro-somatostatin molecule: somatostatin-14 (SS14), the form originally identified from hypothalamic extracts, somatostatin-28 (SS28) and somatostatin 28 (1-12) (SS28 (1-12)). By using antibodies which selectively recognize one or more of these 3 somatostatin-related peptides, we have characterized their immunohistochemical distribution in neocortex. These somatostatin-related peptides have a specific laminar distribution in cortex and are differentially distributed such that SS28 is largely restricted to cell bodies, whereas SS28 (1-12) is preferentially localized in neuronal processes and terminals in a density which far exceeds that revealed by SS-14 immunoreactivity. These data suggest that there may be an intraneuronal transformation from a SS28-like peptide to a SS28 (1-12)-like peptide. In addition, the enriched distribution of nerve fibers containing the antigenic determinant, SS28 (1-12), strongly implies that somatostatin-related peptides constitute a major neurotransmitter system in neocortex. The morphological characteristics of this system are homologous with long projection pathways such as the cortico-cortical specific intrinsic systems as well as projections.

Animals↗

PubMed1983

Effect of 6-hydroxydopamine lesions on norepinephrine-induced [3H]glycogen hydrolysis in mouse cortical slices.

The effects of norepinephrine (NE) on in vitro [3H]glycogenolysis were assessed in slices of cerebral cortex from mice whose cortical noradrenergic innervation had been severely reduced by intracisternal 6-hydroxydopamine (6-OHDA) injections. A supersensitive response to NE was observed, as demonstrated by a decrease in the EC50 of the catecholamine in the lesioned mice from 533 +/- 88 nM to 39.3 +/- 7.9 nM. This supersensitive response, observed two weeks after the lesion, was post-synaptic since isoproterenol, a beta-adrenergic agonist not accumulated by pre-synaptic uptake mechanisms, also gave an equally supersensitive response.

Adrenergic Fibers↗

PubMed1983

Release of somatostatin-28(1-12) from rat hypothalamus in vitro.

Following the discovery of the growth hormone release-inhibiting factor somatostatin from extracts of ovine hypothalamus, an N-terminally extended somatostatin of 28 amino acids has been identified in mammalian tissue. The original peptide, somatostatin-14 (SS14), corresponds to the C-terminus of somatostatin-28 (SS28). Both SS28 and SS14 have biological activity, occur in several rat brain regions, are present in cell bodies and nerve terminals and can be released in vitro upon depolarization in a calcium-dependent manner. Further, high-affinity binding sites were described for SS14, which also bind SS28 (refs 20-23). Recently, a dodecapeptide which corresponds to the N-terminus of somatostatin-28, somatostatin-28(1-12), has been characterized in rat hypothalamus. Radioimmunological and immunohistochemical studies have indicated the presence of SS28(1-12)-like immunoreactivity in several cortical and subcortical regions of the rat brain. This peptide was found to be unevenly distributed with the highest concentration in the hypothalamus, and preferentially localized to dendritic and axonal processes and terminals. These observations suggest that SS28(1-12) may be a neurotransmitter. In this study, we describe a calcium-dependent release of a SS28(1-12)-like peptide from hypothalamic slices in vitro. This finding supports a neurotransmitter function for this peptide.

Animals↗

PubMed1983

Amygdala kindling after ligation of the middle cerebral artery in the rat.

Cerebral infarcts were produced in rats by ligation of the right or left middle cerebral artery. A significant increase in seizure threshold and in the number of days required to develop kindled seizures was found in rats stimulated in the amygdala contralateral to the infarct. However, no significant changes in threshold or kindling rates were found in animals kindled ipsilateral to the ligation. These results were found to be independent of whether the infarct was in the right or left cerebral cortex. These data suggest that contralateral frontoparietal cerebral infarct may have inhibitory influences on seizures originating from the amygdala.

Amygdala↗

PubMed1983

Evidence for dynorphin-A as a neurotransmitter in rat hippocampus.

The molecular forms of Dynorphin A immunoreactivity (Dyn A-IR) detected in hippocampus were resolved by reverse-phase high pressure liquid chromatography (C18-HPLC). Peptide co-eluting with synthetic Dyn A(1-17) represents 20% of the total Dyn A-IR. Dyn A-IR was released from hippocampal slices in vitro by a Ca++-dependent mechanism stimulated by superfusion with K+, kainate or veratrine. Released peptides were resolved by C18-HPLC and shown to contain Dyn A-IR co-eluting with synthetic Dyn A(1-17). These observations are consistent with the hypothesis that Dyn A(1-17) acts as a neurotransmitter at synapses in hippocampus.

Animals↗

PubMed1983

Chemical and physiological aspects of the actions of lithium and antidepressant drugs.

The possible mechanisms underlying the anti-manic actions of lithium have been examined in a variety of interdisciplinary experiments. The possibility that lithium can regulate the sensitivity changes in dopaminergic transmission produced by chronic treatment with haloperidol has been tested. Although a modest modification of behavioral responses to the dopamine agonist apomorphine was found, there was no evidence that this action of lithium reflected alterations of the binding parameters of dopamine-related ligands. In other studies, consistent, dose-dependent increases in brain enkephalin content were found after rats consumed a specially manufactured lithium diet for 2-3 weeks. Not only were brain enkephalin levels increased after this treatment, but some signs of basal analgesic responsiveness also suggested that the elevated levels of enkephalins were functionally significant. To test the possibility that the effects of lithium may not be seen in normal rats, the effects of lithium were compared on spontaneously hypertensive and unaffected, normotensive rats of a related strain. Treatment with lithium altered blood pressure in the hypertensive strain but did not affect blood pressure in the controls. These studies suggest that multiple brain systems may be regulated by treatment with lithium but that the critical pathophysiological process may not be demonstrable in the normal rat.

Animals↗

PubMed1983

Metabolism of [3H]dopamine following intracerebroventricular injection in rats pretreated with ethanol or chloral hydrate.

The metabolism of [3H]dopamine injected into the lateral cerebroventricles, was studied in rats after treatment with either ethanol or chloral hydrate. The experimental system was designed primarily to detect the possible conversion of dopamine to the tetrahydroisoquinoline derivatives, tetrahydropapaveroline, salsolinol and O-methylsalsolinol. With or without pretreatment with ethanol or chloral hydrate, no conversion of [3H]dopamine to [3H]tetrahydroisoquinolines was detected. The limits of detection per rat brain were: tetrahydropapaveroline less than 1.6 X 10(-14) moles (0.00032% conversion), salsolinol less than 1.6 X 10(-13) moles (0.00032% conversion), and 6- and 7-O-methylsalsolinol less than 3.2 X 10(-14) moles (0.00032% conversion). Two consistent ethanol- or chloral hydrate-induced alterations in [3H]dopamine metabolism were noted: (1) small but statistically significant increases in the ratios of reduced to oxidized metabolites resulting from monoamine oxidase action; and (2) decreased relative amounts of N-methylated metabolites.

Animals↗

PubMed1983

Vasopressin potentiation in the performance of a learned appetitive task: reversal by a pressor antagonist analog of vasopressin.

Rats were tested in a simple one-trial water-finding task for the effects of arginine vasopressin (AVP) on performance of an appetitive task. On the training day, each animal was exposed for 5 min to a novel open-field environment that contained a water-tube located in an alcove set into one of the walls of the enclosure. Immediately upon removal from the enclosure, the animals received a subcutaneous injection of either AVP (1 microgram/rat) or vehicle solution. When water-deprived and tested 48 hr later, vasopressin-treated rats found the water tube reliably faster than controls. In other groups of animals, this potentiation in learned performance was prevented by concurrently treating the rats with a vasopressin analog having potent pressor antagonist properties. These results are consistent with the notion that vasopressin may play a role in memory consolidation, but peripheral visceral factors may mediate this action.

Animals↗

PubMed1983

Identifying the protein products of brain-specific genes with antibodies to chemically synthesized peptides.

From the nucleotide sequences of three cDNA clones of rat brain-specific mRNAs, we deduced the partial amino acid sequences of two previously unknown proteins. We raised antisera to synthetic peptides mimicking short regions of these putative brain-specific proteins, and used these sera in immunocytochemical studies to localize each protein in the brain. One protein is found in large neurons throughout the brain, asymmetrically distributed toward the dendritic pole of the cell cytoplasm, suggesting involvement in the synthesis and/or directional transport of dendritic substances. The sequence of the second protein contains pairs of basic residues similar to precursors for neurotransmitters. The protein is located in (and may be the precursor for the neurotransmitter of) a novel fiber network of major extent with ramifications in cerebellum, hippocampus, and cortex, and in cell bodies in the brain stem, hypothalamus, and caudate nucleus. Our approach provides a direct method for characterizing rare brain molecules which may not have been anticipated and for which there are no known functional assays.

Amino Acid Sequence↗

PubMed1983

Plasma measures of beta-endorphin/beta-lipotropin-like immunoreactivity in chronic pain syndrome and psychiatric subjects.

This study compared basal concentrations of plasma beta-endorphin/beta-lipotropin-like immunoreactivity and dexamethasone suppression of cortisol in seven chronic pain patients, seven psychiatric disorder patients, and seven normal volunteers. Pain patients and psychiatric patients showed significantly higher basal concentrations of beta-endorphin/beta-lipotropin-like immunoreactivity compared to normal volunteers. Pain patients also had significantly higher beta-endorphin/beta-lipotropin-like immunoreactivity than psychiatric patients, even though there was no significant difference in severity of depressive symptomatology as assessed by Beck and Hamilton scores. Resistance to dexamethasone occurred in 57% of pain patients. These results may indicate that biological markers for depression occur in populations of chronic pain patients, or may reflect levels of central nervous system arousal in response to stress, pain, or nonaffective phenomena.

Adult↗

PubMed1983

Can aversive properties of (peripherally-injected) vasopressin account for its putative role in memory?

Rats injected with arginine vasopressin (AVP) immediately after exposure to a novel open-field environment found a water tube faster than saline injected rats, when water-deprived 48 h later. Other experiments demonstrated that this effect did not result from some conditioned or pharmacologically-induced hyperactivity in the experimental group. Although these results are consistent with a role for AVP in 'memory' mechanisms, lithium chloride, a known illness-producing agent, produced a reduction in latency to find the water tube identical to that of AVP. In separate experiments, AVP acted as an effective unconditioned stimulus in conditioned taste and place aversion studies. AVP also produced a dose-dependent disruption of spontaneous locomotor activity. Together, these data indicate that peripheral AVP administration has aversive consequences. Desglycinamide arginine vasopressin (an AVP analog with weak pressor-agonist properties) produced no observable aversive effects and did not improve test performance in the appetitive water-finding task. It is suggested that the apparent memory-enhancing properties of peripherally administered AVP, at least in appetitive test paradigms, may depend on its aversive and consequently arousing actions.

Animals↗

PubMed1983

A possible high molecular weight precursor to vasoactive intestinal polypeptide sequestered into pheochromocytoma chromaffin granules.

Chromaffin granules, the catecholamine storage granules of pheochromocytoma were isolated from five human pheochromocytoma tumors. Vasoactive intestinal polypeptide (VIP) immunoreactivity was detected in all chromaffin granule preparations, paralleling the synthetic VIP antibody binding curve over a range of serial dilutions. In addition, gel filtration revealed an immunoreactive peptide peak coeluting with VIP. However, high molecular weight immunoreactive material was also detected on the column. This high molecular weight material was further characterized by sodium dodecyl sulfate gel electrophoresis, followed by electroblotting onto nitrocellulose paper and detection by anti-VIP antibodies with a secondary antibody conjugated to horseradish peroxidase. A 70 000 dalton immunoreactive band was identified, in which reactivity with anti-VIP antibody was inhibited by VIP; this band did not cross react with non-related antibodies. This 70 000 dalton protein may be an intermediate molecule in the biosynthesis and processing of VIP.

Adrenal Gland Neoplasms↗

PubMed1983

Effects of cysteamine on pro-somatostatin related peptides.

Intracerebroventricular (icv) injection of cysteamine to rats produced a marked depletion of somatostatin-14-like immunoreactivity (LI) in all rat brain regions examined. The somatostatin-28 (SS28)-LI and SS28(1-12)-LI were generally not altered by the cysteamine treatment. Following subcutaneous injection of the drug similar depletions of hypothalamic SS14-LI was observed with no change in SS28-LI nor SS28(1-12)-LI. In vitro cysteamine significantly increased the basal release of SS14-LI and markedly potentiated the evoked release of SS14-LI from hypothalamic slices. At 10 mM cysteamine, enhanced release of SS14-LI from hypothalamic slices was still observed despite a marked depletion of tissue content of SS14-LI.

Animals↗

PubMed1983

Functional receptors for vasoactive intestinal polypeptide in cultured astroglia from neonatal rat brain.

The effects of vasoactive intestinal polypeptide (VIP) were assessed on astroglia cultured from rat CNS. In these cultures VIP (500 nM) promoted the hydrolysis of [3H]glycogen newly synthesized from [3H]glucose. This effect on [3H]glycogen levels was also observed with the structurally related peptide PHI-27 and with other substances which had been demonstrated to promote glycogenolysis in rodent CNS in vitro such as: norepinephrine (NE), serotonin, histamine, adenosine, K+ and dibutyryl cyclic-AMP (dbcAMP). Furthermore, VIP (500 nM) and PHI 27 (500 nM), when applied to astroglial cultures in serum-free medium, displayed marked effects on the morphological appearance of the cell population: they converted the flat cells present in the cultures into cells with typical astrocytic morphology. As previously reported, this effect on the cellular morphology of the cultures was also observed, under identical experimental conditions, after NE and dbcAMP application. These studies demonstrate that cultured rat neonatal astroglia possess receptors for VIP, and suggest that a cyclic AMP accumulation may mediate both the metabolic and morphologic components of this response.

Animals↗