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Moshe Rehavi

Bio: Moshe Rehavi is an academic researcher from Tel Aviv University. The author has contributed to research in topics: Imipramine & Serotonin. The author has an hindex of 31, co-authored 115 publications receiving 3427 citations.


Papers
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Journal ArticleDOI
TL;DR: Prenatal immune activation induced by peripheral administration of the synthetic cytokine releaser polyriboinosinic–polyribocytidilic acid to pregnant dams may provide a neurodevelopmental model of schizophrenia that reproduces a putative inducing factor; mimics the temporal course as well as some central abnormalities of the disorder; and predicts responsiveness to antipsychotic drugs.

463 citations

Journal ArticleDOI
TL;DR: These results, coupled with previous studies showing a significant decrease in the maximal uptake of serotonin in platelets from depressed patients, suggest that an inherited or acquired deficiency of the serotonin transport protein or proteins may be involved in the pathogenesis of depression.
Abstract: The high-affinity tritiated (3H) imipramine binding sites are functionally (and perhaps structurally) associated with the presynaptic neuronal and platelet uptake sites for serotonin. Since there is an excellent correlation between the relative potencies of a series of antidepressants in displacing 3H-imipramine from binding sites in human brain and platelet, we have examined the binding of 3H-imipramine to platelets from 14 depressed patients and 28 age- and sex-matched controls. A highly significant decrease in the number of 3H-imipramine binding sites, with no significant change in the apparent affinity constants, was observed in platelets from the depressed patients compared with the controls. These results, coupled with previous studies showing a significant decrease in the maximal uptake of serotonin in platelets from depressed patients, suggest that an inherited or acquired deficiency of the serotonin transport protein or proteins may be involved in the pathogenesis of depression.

314 citations

Journal ArticleDOI
TL;DR: The lower density of [3H]imipramine binding sites in platelet membrane in patients with obsessive-compulsive disorder might implicate involvement of the serotonergic system or might represent an adaptive response to a chronic disease.
Abstract: The authors evaluated high-affinity [3H]imipramine binding and [3H]serotonin uptake to platelets in eight adolescent and 10 adult patients who met DSM-III criteria for obsessive-compulsive disorder in comparison with those of normal control subjects of similar ages The maximal binding of [3H]imipramine was significantly lower in adults and adolescents with obsessive-compulsive disorder than in the control subjects No differences between groups in the affinity of [3H]imipramine to its binding sites or in serotonin uptake kinetic measures were detected The lower density of [3H]imipramine binding sites in platelet membrane in patients with obsessive-compulsive disorder might implicate involvement of the serotonergic system or might represent an adaptive response to a chronic disease

112 citations

Journal ArticleDOI
TL;DR: There is a growing need to incorporate this increasingly complex body of knowledge to the standard curriculum of medical schools, so that the forthcoming generation of clinicians and researchers will be familiar with the latest developments in pharmacogenomics and medical bioinformatics.

105 citations

Journal ArticleDOI
TL;DR: It is suggested that the increase in alpha-adrenergic as well as in muscarinic binding is a consequence of a chronic blockade of these two types of receptors by amitriptyline in vivo.

93 citations


Cited by
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Journal ArticleDOI
TL;DR: Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity.
Abstract: This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.

1,567 citations

Journal ArticleDOI
TL;DR: This work has shown that estrogens, Neuroprotection, and Alzheimer’s Disease are intertwined and that the effects of estrogens on learning and memory are determined by the mechanism of action of the hormone.
Abstract: I. Introduction II. Mechanisms of Estrogen Action A. “Genomic” and “nongenomic” mechanisms B. Steroid hormone actions on gene expression C. Subtypes of estrogen receptors D. Steroid hormone actions on putative receptors on membranes E. Rapid actions of steroids on neuronal excitability F. Steroid hormone actions via second messengers G. Neuroprotective effects of estrogens H. Summary III. Areas of the Brain Affected Outside of the Hypothalamus A. Studies of hypothalamic and extrahypothalamic actions of estrogens B. Estrogens and the cholinergic system C. Estrogens and the serotonergic system D. Catecholaminergic neurons E. Spinal cord F. Hippocampus G. Glial cells, endothelial cells, and the blood-brain barrier H. Summary IV. Effects of Estrogens on Learning and Memory V. Estrogens, Neuroprotection, and Alzheimer’s Disease VI. Conclusions

1,477 citations

Journal ArticleDOI
TL;DR: It is shown that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring and should be identified as a key intermediary in the molecular dissection of the pathways whereby MIA alters fetal brain development.
Abstract: Schizophrenia and autism are thought to result from the interaction between a susceptibility genotype and environmental risk factors. The offspring of women who experience infection while pregnant have an increased risk for these disorders. Maternal immune activation (MIA) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism, making MIA a useful model of the disorders. However, the mechanism by which MIA causes long-term behavioral deficits in the offspring is unknown. Here we show that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring. A single maternal injection of IL-6 on day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent inhibition (LI) deficits in the adult offspring. Moreover, coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA prevents the PPI, LI, and exploratory and social deficits caused by poly(I:C) and normalizes the associated changes in gene expression in the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does not result in several of the behavioral changes seen in the offspring of wild-type mice after MIA. The identification of IL-6 as a key intermediary should aid in the molecular dissection of the pathways whereby MIA alters fetal brain development, which can shed new light on the pathophysiological mechanisms that predispose to schizophrenia and autism.

1,336 citations

Journal ArticleDOI
TL;DR: Several studies support the hypothesis that major depression is associated with a state of reduced DA transmission, possibly reflected bycompensatory up-regulation of D2receptors, and further research on the contribution of DA to the pathophysiology of depression is justified to improve outcomes for patients with treatment-resistant and nonremitting depression.
Abstract: Multiple sources of evidence support a role for diminished dopaminergic neurotransmission in major depression. The physiological alterations underlying reduced dopamine(DA)signalingcouldresultfromeitherdiminishedDAreleasefrompresynaptic neuronsorimpairedsignaltransduction,eitherduetochangesinreceptornumberor functionand/oralteredintracellularsignalprocessing.Therearedatasupportingeachofthesemechanisms,althoughinterpretationofpreviousresearchisconfoundedbyissuesaroundstudypopulation, medication status, and technological limitations. In some patients with depression, DA-related disturbances improve by treatment with antidepressants, presumably by acting on serotonergic or noradrenergic circuits, which then affect DA function. However, most antidepressant treatments do not directly enhance DA neurotransmission, which may contribute to residual symptoms, including impaired motivation, concentration, and pleasure. Animal models of major depression show considerable responsiveness to manipulations of DA neurotransmission. Several studies, including postmortem investigations, particularly of subjects with severe depression, have demonstrated reduced concentrations of DA metabolites both in the cerebrospinal fluid and in brain regions that mediate mood and motivation. Although the neuroimaging findings are not unequivocal, several studies support the hypothesis that major depression is associated with a state of reduced DA transmission, possiblyreflectedbyacompensatoryup-regulationofD2receptors.ThesealterationsinDAsignalingmay underlie the findings of increased “liking” or “high” feelings reported by severely depressed subjects treated with d-amphetamine compared with the response of less severely ill and normal control subjects. The efficacy of medications that directly act on DA neurons or receptors, such as monoamine oxidase inhibitors and pramipexole, suggests that subtypes of depression stemming from a primary DA dysfunction exist. Further research on the contribution of DA to the pathophysiology of depressionisjustifiedtoimproveoutcomesforpatientswithtreatment-resistantandnonremittingdepression.

1,104 citations

Journal ArticleDOI
07 Nov 1991-Nature
TL;DR: A large family of related gene products expressed in rodent brain is identified from two highly conserved regions of the transporters for noradrenaline and γ-aminobutyric acid, and one of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex.
Abstract: SELECTIVE antagonism of serotonin (5-hydroxytryptamine, 5HT) and noradrenaline transport by antidepressants is a key element in the 'amine' hypothesis of affective disorders1. Uptake2,3 and/or transport sites4,5 of 5HT have been reported to be reduced in platelets of patients suffering from depression and in post-mortem brain samples of depressed patients6 and suicide victims7. To date there has been little molecular information available on the structure and regulation of 5HT transporters. Using the polymerase chain reaction8with degenerate oligonucleotides9 derived from two highly conserved regions of the transporters for noradrenaline10 and γ-aminobutyric acid11(GABA), we have identified a large family of related gene products expressed in rodent brain. One of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex. Transfection with a single 2.3-kilobase brainstem complementary DNA clone is sufficient to confer expression of a Na+-dependent 5HT transporter upon non-neural cells, with transport selectively and potently antagonized by 5HT uptake-specific antidepressants, including paroxetine, citalopram and fluoxetine.

829 citations