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J Epelbaum

Publications and source records attributed to J Epelbaum.

176 records · Page 10Linked to original sources
PubMed1976

In vitro release of luteinizing hormone-releasing hormone (LHRH) from rat mediobasal hypothalamus: effects of potassium, calcium and dopamine.

A suitable preparation to study the effect of dopamine (DA) on in vitro LHRH secretion is presented. Enzymatic degradation of LHRH in the incubation medium is completely inhibited by bacitracin (2 X 10(-5) M). Ahigh potassium concentration (56mM) induces an increase in LHRH release from entire pieces of mediobasal hypothalamus (MBH), but not from a synaptosomal pellet; this release is inhibited when calcium is omitted. The depolarization-induced LHRH in the MBH. In contrast, DA (10(-6)M) is not effective in vitro on MBH from ovariectomized rats but induces a fast release of LHRH from MBH of normal male and estradiol-pretreated ovariectomized rats. The preparation presented here appears to be of great interest in investigating amine-steroid-LHRH interactions at the cellular level.

Animals↗
PubMed1975

Distribution of LH-RH in subcellular fractions of the basomedial hypothalamus.

Subcellular fractionation of the mediobasal hypothalamus (MBH) and other brain structures was achieved by differential and sucrose gradient centrifugation. The fractions were monitored by measuring lactate dehydrogenase (LDH) activity (a marker for the soluble cytoplasmic fraction) and by electron microscopic examination. The luteinizing-hormone-releasing-hormone (LH-RH) content of the fractions was evaluated both by bioassay and radioimmunoassay. Significant amounts of LH-RH were found only in the MBH and in an anterobasal location corresponding to the organum vasculosum of the lamina terminalis. Within these areas, LH-RH activity was present in the first supernatant (homogenate with the exclusion of the nuclear pellet). Seventy percent of the LH-RH activity was recovered in the crude mitochondrial fraction. After further fractionation on a sucrose gradient, the distribution of LH-RH was parallel with that of LDH activity. Since LDH is predominantly located in the synaptosomal soluble fraction, it is concluded that the vast majority of LH-RH is contained within nerve endings. This finding is consistent with cyto-immunological data on the distribution of the neuropeptide in the rat hypothalamus.

Animals↗
PubMedDate not supplied

Autoradiographic localization of a non-reducible somatostatin analog (125I-CGP 23996) binding sites in the rat brain: comparison with membrane binding.

The regional distribution of somatostatin binding sites in the rat brain was determined by quantitative autoradiography, using 125I-CGP 23996, a non-reducible somatostatin analog. In preliminary experiments, kinetic properties of 125I-CGP 23996 binding to rat brain membranes and slide mounted frozen brain sections were compared and found similar. In addition, distribution of 125I-CGP 23996 and 125I-N-Tyr-SRIF14 binding sites on membrane prepared from 10 different rat brain structures were closely correlated (r = 0.91, 2 p less than 0.01), indicating that the non-reducible analog recognizes the same binding site as the Tyr-extended native peptide. Highest levels of 125I-CGP 23996 binding sites were found in anterior temporal, frontal and cingular cortex as well as hippocampus. Moderate levels were found in the remaining part of the limbic system including amygdala, olfactory tubercles and bed nucleus of the stria terminalis. In the brain stem, nuclei involved in the auditory system such as the ventral cochlear nucleus and the superior olive nucleus, contained high levels of 125I-CGP 23996 binding sites. The distribution of 125I-CGP 23996 binding sites roughly correlated with that of the endogenous peptide in most structures, except in the mediobasal hypothalamus.

Amygdala↗
PubMedDate not supplied

125I-[Tyr0,D-Trp8]somatostatin-14 binding sites in the locus coeruleus of the rat are located on both ascending and descending projecting noradrenergic cells.

Radioautographic determinations of 125I-[Tyr0,D-Trp8]somatostatin-14 (125I-SRIF) binding sites were performed on frozen serial sections of the locus coeruleus (LC) of control rats and of rats subjected to either bilateral microinjections of 6 hydroxydopamine (6-OHDA) into the LC or unilateral microinjection into the ascending noradrenergic bundles. These experiments were performed in order to determine whether 125I-SRIF binding was localized to noradrenergic-containing cells and in which regions the cells which contain the binding sites are projecting. The extent of the lesions was assessed by measuring norepinephrine (NE) levels in the hippocampus (88% decrease as compared to sham-operated animals) for bilateral LC lesions and in the frontal cortex (87% reduction vs. contralateral side) for unilateral bundle lesions. In control rats, 125I-SRIF binding sites were restricted to the boundaries of the LC and followed closely the distribution of tyrosine hydroxylase-labeled cells. Three weeks after bilateral injections of 6-OHDA, 125I-SRIF binding decreased by 79% in all regions of the LC. In contrast, unilateral destruction of the ascending noradrenergic bundles resulted in a moderate decrease only in the middle part of the LC with a more important effect in the dorsal (55%) than in the ventral (24%) portion of the nucleus. These data demonstrate that: 1) most SRIF receptors in the LC are located in the vicinity of NE-containing cell bodies and 2) NE-containing cells bearing SRIF receptors project to the forebrain as well as to other terminal areas located more caudally in the brain. These data suggest a general role for SRIF in the control of the multiple functions of the LC.

Animals↗
PubMedDate not supplied

Choline acetyltransferase and somatostatin levels in aged Microcebus murinus brain.

beta-Amyloid protein (beta-AP) deposits, analoguous to those found in Alzheimer's disease (AD) are observed in the brain of aging Microcebus murinus. Because choline acetyltransferase (ChAT) activity and somatostatin (SRIH) content are consistently decreased in AD, we tested whether such changes could be observed in middle aged to aged Microcebus cerebral cortex and whether they were accompanied by beta-AP deposits. A positive correlation was observed between age and ChAT activity. By HPLC, SRIH immunoreactivity eluted as four peaks, two of which being identical with SRIH-28 and SRIH-14 while the other two likely represented precursor forms. Cortical SRIH content was not significantly affected by age. ChAT activity and SRIH content were not significantly correlated. Amyloid angiopathy was observed in every brain examined and the presence of cortical lesions analoguous to senile plaques observed in the oldest case only which did not demonstrate important alterations in ChAT and somatostatin levels.

Aging↗
PubMedDate not supplied

Differential correlation between neurochemical deficits, neuropathology, and cognitive status in Alzheimer's disease.

The relationships between neurofibrillary tangles (NFT), senile plaques (SP), and the deficits in somatostatin (SRIH) and choline acetyltransferase (ChAT) levels were determined in Brodmann area 9, 40, 22, and 17/18 in 12 women whose Blessed test score (BTS) ranged from 27 to 1. NFT density correlated with the cognitive decline in areas 9, 40, and 22 and with SP number in area 22 and 17/18. ChAT levels were linked to the BTS in area 9, 40, and 22 and SRIH levels in area 9 only. ChAT, but not SRIH, did correlate with SP (area 22) and NFT (area 40 and 22). Decreases in ChAT and SRIH were correlated in areas 9 and 22. These results indicate that the somatostatinergic deficit in Alzheimer's disease is more regionally restricted than the cholinergic one. The correlation between SRIH and ChAT as observed in area 9 and 22 may indicate that somatostatin- and acetylcholine-containing elements in the frontal and temporal lobes are particularly relevant to the cognitive decline as observed in Alzheimer's disease.

Aged↗
PubMedDate not supplied

Light microscopic radioautographic localization of somatostatin binding sites in the brainstem of the rat.

The distribution of somatostatin binding sites was investigated by light microscopic radioautography in the brainstem of the rat following in vitro labeling with 125I-Tyr0-DTrp8-somatostatin14. Moderate to high labeling densities were detected within the superior colliculus, the locus coeruleus and subcoeruleus, the parabrachial complex, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus. Most of the white matter was devoid of specific somatostatin binding except for fibers of the glossopharyngeal nerve and the spinal trigeminal tract. In most of the labeled areas, 125I-somatostatin binding was evenly distributed between neuropil and perikarya. In a few instances, however, the binding clearly predominated over nerve cell bodies: namely in the dorsal motor nucleus of the vagus and in the pontine and medullary tegmentum. In the latter two regions, the labeled neurons were identified in adjacent sections by tyrosine hydroxylase immunohistochemistry as belonging to the A5 and A1 catecholamine cell groups, respectively. These findings, together with the confirmed association of somatostatin binding sites with noradrenergic neurons in the locus coeruleus, suggest that interactions with catecholaminergic systems may represent a major mode of action for somatostatin in the brainstem.

Animals↗
PubMedDate not supplied

Somatostatin and behaviour: the need for genetically engineered models.

Somatostatin was originally characterised as a hypothalamic neurohormone responsible for the inhibition of pituitary Growth Hormone secretion. In mammals two genes encode for somatostatin-related peptides, somatostatin 14 and 28, and cortistatins, respectively. All peptides bind with similar affinities to the five cloned somatostatin receptors (sst), which belong to the GPCR family. Despite numerous studies, no clear behavioural function has yet been attributed to somatostatin-related peptides. This is due to the lack of good pharmacological tools (selective antagonists) and animal models. This review will focus on the recent development of such tools.

Animals↗
PubMedDate not supplied

[In vitro study of the interaction between neuromediators and neuropeptides involved in hypothalamic neurosecretion control (author's transl)].

Luteinizing hormone-releasing hormone (LHRH) and somatostatin (SRIF) release was assessed in superfused slices of mediobasal hypothalamus. Release of both neurohormones by depolarizing agents (K+, 56mM ; veratridine, 50 muM) was shown to be Ca2+-dependent, according with the stimulus-secretion coupling hypothesis. Opiates (beta endorphin, 10(-7)M and D-ALA2-Met-enkephalinamide 10(-7)M) did not alter the spontaneous release of LHRH and SRIF, but inhibited significantly the K+-induced neuropeptide release. The effect was reversed by the opiate antagonist naloxone (10(-7)M), while naloxone was ineffective by itself. Vasoactive intestinal peptide (VIP 10(-9)M) significantly inhibited K+ evoked release of SRIF ; LHRH release was unaffected. The effect of VIP on SRIF release was dose-dependent ; secretin, a partial VIP agonist, was also active at higher doses. The data suggest that : 1) opiates, acting through specific opiate receptors located on LHRH and SRIF neurons, modulate the release of the neurohormones ; 2) the inhibitory effect of opiates could be due to an inhibition of calcium influx through voltage-dependent calcium channels ; 3) this interaction may account for the stimulation of growth hormone and the inhibition of luteinizing hormone observed after systemic administration of opiates ; 4) VIP inhibits SRIF release, by acting on VIP receptors present on MBH SRIF terminals ; the effect is consistent with the stimulation of GH reported after in vivo administration of the peptide.

Endorphins↗