Stress differentially regulates synaptophysin and synaptotagmin expression in hippocampus

Thome, Johannes; Pesold, Brigitte; Baader, Miriam; Hu, Mei; Gewirtz, Jonathan C.; Duman, Ronald S.; Henn, Fritz A.

doi:10.1016/s0006-3223(01)01229-x

Cited by 115 publications

(72 citation statements)

References 24 publications

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“…The fact that synaptic proteins were found unchanged in the DG of LH animals suggests the regional specificity for the stress-induced synaptic changes. These results are in line with those reported by Thome et al (2001) and Kuroda and McEwen (1998) showing, respectively, diminished SYN and GAP-43 mRNA levels in stressed rats and support the hypothesis that brain plasticity might be disturbed in experimental models of depression (Duman, 2002).…”

Section: Modulation Of Synaptic Plasticity By Antidepressantssupporting

confidence: 92%

“…Synapses have also been found to underlie functional and morphological changes under stress conditions. It is known that chronic stress induces structural remodeling of excitatory axo-spinous synaptic connectivity (Donohue et al, 2006) and differentially regulates synaptic protein expression in the hippocampus (Thome et al, 2001;Rosenbrock et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Maintenance Treatment with Fluoxetine is Necessary to Sustain Normal Levels of Synaptic Markers in an Experimental Model of Depression: Correlation with Behavioral Response

Reinés

Cereseto

Ferrero

et al. 2007

Neuropsychopharmacol

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Dysfunction of hippocampal plasticity has been proposed to play a critical role in the pathophysiology of depression. However, antidepressant drug effects on synaptic plasticity and cytoskeletal remodeling remain controversial. The aim of the present study was to evaluate in animals exposed to the learned helplessness (LH) paradigm, an accepted experimental model of depression, the effect of chronic treatment with fluoxetine (FLX) on synaptic and cytoskeletal proteins known to undergo plastic changes. Synaptophysin (SYN), postsynaptic density 95 (PSD-95), axon growth-associated protein 43 (GAP-43), and cytoskeletal proteins (intermediate neurofilaments and MAP-2) were studied in the hippocampus by immunohistochemistry. Whereas LH animals treated 21 days with saline (LH-S group) displayed diminished SYN and PSD-95 immunostainings in the CA3 but not in the DG, chronic treatment with FLX not only reversed the despaired behavior induced by exposure to LH paradigm, but also fully recovered SYN and PSD-95 labeling to control values. Similar results were obtained for the axonal remodeling marker GAP-43. FLX treatment did not modify either the decreased light neurofilament subunit (NFL) observed in the hippocampus of LH animals or any other cytoskeletal protein studied. When FLX treatment was withdrawn for 90 days in those LH-FLX animals in which reversion of despair had been observed at day 25, recurrence of despaired behavior was found accompanied by decreased SYN, PSD-95, and NFL labelings. Results indicate that the synapse remodeling induced by FLX in the CA3 region could underlie its behavioral efficacy despite the absence of cytoskeletal remodeling and that the stability of synaptic changes would depend on the continuous administration of the drug.

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Section: Modulation Of Synaptic Plasticity By Antidepressantssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Maintenance Treatment with Fluoxetine is Necessary to Sustain Normal Levels of Synaptic Markers in an Experimental Model of Depression: Correlation with Behavioral Response

Reinés

Cereseto

Ferrero

et al. 2007

Neuropsychopharmacol

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show abstract

“…11 These changes, opposite to those seen for fluoxetine and tranylcypromine here, may be part of the neural adaptation to stress. These plastic changes may play a role in the hippocampal alterations observed in stressrelated disorders such as depression and post-traumatic stress disorder.…”

Section: Discussionmentioning

confidence: 53%

Differential regulation of synaptic vesicle proteins by antidepressant drugs

Rapp

Baader

et al. 2004

Pharmacogenomics J

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Synaptic vesicle proteins (SVP) play a critical role in neurotransmitter release and neural plasticity, and have been implicated in the pathophysiology of psychiatric disorders such as depression. Antidepressant drugs not only alter the level of neurotransmitters, but also modulate de novo gene transcription and synthesis of proteins involved in neural plasticity. In order to investigate the effects of antidepressant compounds on SVP-mRNA levels, the expressions of synaptophysin, synaptotagmin, VAMP, and synapsin-I were analysed by in situ hybridization in rats which had been treated with desipramine, fluoxetine, tranylcypromine, or saline. The results demonstrate that chronic treatment with fluoxetine and tranylcypromine leads to an increased expression of synaptophysin, but decreased expression of synaptotagmin and VAMP in the hippocampus and cerebral cortex. Additionally, synapsin ImRNA levels in the hippocampus and cerebral cortex are significantly reduced in tranylcypromine-treated animals. This identifies SVP genes as target genes of antidepressant treatment. Keywords: depression; psychopharmacology; psychosis; SSRI; synapsin; synaptophysin INTRODUCTION Synaptic vesicle proteins (SVP) such as synapsin I-III, synaptophysin, synaptotagmin, and synaptobrevin (VAMP -vesicle-associated membrane protein) play a critical role in synaptic plasticity, and are required for vesicle fusion and neurotransmitter release. [1][2][3][4][5][6] Hence, changes in the expression of these proteins may contribute to the molecular effects of antidepressant treatment and associated behavioral and cognitive alterations. Previous studies have shown that antidepressants modulate de novo gene transcription and synthesis of proteins involved in neural and synaptic plasticity; in a recent transcriptomic study, a decreased expression of VAMP was found with imipramine and sertraline. 7 In order to investigate the effects of antidepressant compounds on synaptic plasticity, the expression of SVP was analysed by in situ hybridization in rats which had been treated with desipramine, fluoxetine, tranylcypromine, or saline (control group) for 2 weeks.

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“…Contrary to this hypothesis, we found that synaptophysin mRNA was unaltered dentate gyrus and indeed was also unchanged in CA3. In a recent report it was shown that both acute and chronic restraint stress markedly reduced synaptophysin mRNA in hippocampus (Thome et al, 2001). These data suggest a role for corticosterone in the regulation of synaptophysin mRNA, but may indicate that such regulation occurs only with the magnitude of increase in corticosterone associated with restraint stress rather than with the moderate changes to the corticosterone rhythm used here.…”

Section: Corticosterone-induced Changes In Hippocampal Expression Of mentioning

confidence: 47%

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

Gartside

Leitch

McQuade

et al. 2002

Neuropsychopharmacol

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Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calciumcalmodulin dependent kinase (CAMKIIa) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

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Stress differentially regulates synaptophysin and synaptotagmin expression in hippocampus

Cited by 115 publications

References 24 publications

Maintenance Treatment with Fluoxetine is Necessary to Sustain Normal Levels of Synaptic Markers in an Experimental Model of Depression: Correlation with Behavioral Response

Maintenance Treatment with Fluoxetine is Necessary to Sustain Normal Levels of Synaptic Markers in an Experimental Model of Depression: Correlation with Behavioral Response

Differential regulation of synaptic vesicle proteins by antidepressant drugs

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

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