Cortistatin and somatostatin mRNAs are differentially regulated in response to kainate

Calbet, Marta; Guadaño-Ferraz, Ana; Spier, Avron D.; Maj, Marcin; Sutcliffe, J. Gregor; Przewłocki, Ryszard; Lecea, Luı́s de

doi:10.1016/s0169-328x(99)00220-x

Cited by 31 publications

(9 citation statements)

References 57 publications

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“…Thus, although cortistatin and somatostatin share similar pharmacological characteristics at the known SSTRs, the localization of cortistatin in neurons with a connectivity different from that of somatostatinergic neurons may enable distinct SSTRmediated functions of both peptides in the cortical circuitry. The regulation pattern of cortistatin and somatostatin we observed after MCAO was completely different from the regulation of these genes in a kainic acid seizure model, in which somatostatin expression was strongly increased in pyramidal cells and cortistatin expression was unaltered (Calbet et al, 1999). To our knowledge, we provide the first report of sustained downregulation of cortistatin expression after cortical lesion.…”

Section: Regulation Of Somatostatin and Cortistatin In Gabaeric Corticontrasting

confidence: 75%

Somatostatin Receptor 2 Is Activated in Cortical Neurons and Contributes to Neurodegeneration after Focal Ischemia

Stumm¹,

Zhou²,

Schulz³

et al. 2004

J. Neurosci.

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Somatostatin receptor 2 (SSTR2) mediates neuromodulatory signals of somatostatin and cortistatin in the cerebral cortex. Recently, SSTR2 has been shown to enhance conserved death ligand-and mitochondria-mediated apoptotic pathways in non-neuronal cells. Whether somatostatin receptors are activated in cerebrocortical neurons and contribute to neurodegeneration after experimental focal ischemia was unknown until now. Here we examined internalization of SSTR2 in a rat model of middle cerebral artery occlusion (MCAO) by confocal microscopy. At 3 and 6 hr after MCAO, SSTR2 was internalized excessively in cerebrocortical neurons adjacent to the infarct, which was prevented by intracerebroventricular application of the SSTR2-selective antagonist BIM-23627. SSTR2 internalization was associated with a transient depletion of somatostatin from axonal terminals and increased expression of SSTR2 mRNA. The initial loss of somatostatin was followed by an increase in somatostatin mRNA levels, whereas cortistatin mRNA expression was decreased. In SSTR2-deficient mice with lacZ under the control of the SSTR2 promoter, MCAO-induced upregulation of SSTR2 gene expression was less pronounced than in wild types. SSTR2-deficient mice exhibited a 40% reduction of infarct size after permanent distal MCAO and a 63% reduction after transient proximal MCAO. In summary, we provide direct evidence for activation of SSTR2 by an endogenous ligand after focal ischemia. Activation of functional SSTR2 receptors contributes to increased SSTR2 gene expression and postischemic neurodegeneration.

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Section: Regulation Of Somatostatin and Cortistatin In Gabaeric Corticontrasting

confidence: 75%

Somatostatin Receptor 2 Is Activated in Cortical Neurons and Contributes to Neurodegeneration after Focal Ischemia

Stumm¹,

Zhou²,

Schulz³

et al. 2004

J. Neurosci.

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“…There is also evidence that some of the physiological effects of CST are different from those of SRIF. For example, unlike SRIF, CST is not upregulated significantly by seizure‐induced increase in neural activity (Calbet et al ., 1999). Rather, recent results demonstrate that CST expression is increased by kainic acid‐induced status epilepticus in immature rat hippocampus and suggest that CST overexpression may prevent neuronal loss after seizure in adults (Wilson et al ., 2005).…”

Section: Discussionmentioning

confidence: 99%

Compensatory changes in the hippocampus of somatostatin knockout mice: upregulation of somatostatin receptor 2 and its function in the control of bursting activity and synaptic transmission

Cammalleri

Cervia

Monte

et al. 2006

Eur J of Neuroscience

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Somatostatin-14 (SRIF) co-localizes with gamma-aminobutyric acid (GABA) in the hippocampus and regulates neuronal excitability. A role of SRIF in the control of seizures has been proposed, although its exact contribution requires some clarification. In particular, SRIF knockout (KO) mice do not exhibit spontaneous seizures, indicating that compensatory changes may occur in KO. In the KO hippocampus, we examined whether specific SRIF receptors and/or the cognate peptide cortistatin-14 (CST) compensate for the absence of SRIF. We found increased levels of both sst2 receptors (sst2) and CST, and we explored the functional consequences of sst2 compensation on bursting activity and synaptic responses in hippocampal slices. Bursting was decreased by SRIF in wild-type (WT) mice, but it was not affected by either CST or sst2 agonist and antagonist. sst4 agonist increased bursting frequency in either WT or KO. In WT, but not in KO, its effects were blocked by agonizing or antagonizing sst2, suggesting that sst2 and sst4 are functionally coupled in the WT hippocampus. Bursting was reduced in KO as compared with WT and was increased upon application of sst2 antagonist, while SRIF, CST and sst2 agonist had no effect. At the synaptic level, we observed that in WT, SRIF decreased excitatory postsynaptic potentials which were, in contrast, increased by sst2 antagonist in KO. We conclude that sst2 compensates for SRIF absence and that its upregulation is responsible for reduced bursting and decreased excitatory transmission in KO mice. We suggest that a critical density of sst2 is needed to control hippocampal activity.

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“…SST mRNA expression and immunoreactivity are remarkably enhanced in the soma of interneurons in the hilus and stratum oriens of CA1 and CA3, and their projections in outer molecular layer and stratum lacunosum moleculare one day to one month after hippocampal kindling (Schwarzer et al, 1996;Wanscher et al, 1990). Interestingly, ectopic expressing of SST in dentate granule cells has also been demonstrated after seizures (Calbet et al, 1999;Hashimoto and Obata, 1991).…”

Section: Sst Release and Expression Is Upregulated By Seizuresmentioning

confidence: 99%

Somatostatin: An endogenous antiepileptic

Tallent

Qiu

2008

Molecular and Cellular Endocrinology

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The neuropeptide somatostatin is highly expressed in brain regions associated with seizures. In hippocampus, SST expression and release is regulated by seizures, and SST-containing neurons within the hilus of the dentate gyrus are sensitive to seizure-induced death. In vivo and in vitro studies suggest that the loss of SST function in the dentate could contribute to epileptogenesis and seizure susceptibility. SST also has inhibitory actions in the CA1 and CA3 hippocampus, indicating this peptide is an important homeostatic regulator throughout the hippocampus. In vivo studies show SST has robust antiepileptic properties, with the major site of action being hippocampus. In rodents, somatostatin receptor subtype 2 (SST 2 ) and SST 4 appear to mediate the majority of the antiepileptic actions of SST, with SST 2 predominate in rat and SST 4 in mouse. Thus SST receptors may be appropriate targets for new antiepileptic drugs, although validation in human tissue is lacking.

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Cortistatin and somatostatin mRNAs are differentially regulated in response to kainate

Cited by 31 publications

References 57 publications

Somatostatin Receptor 2 Is Activated in Cortical Neurons and Contributes to Neurodegeneration after Focal Ischemia

Somatostatin Receptor 2 Is Activated in Cortical Neurons and Contributes to Neurodegeneration after Focal Ischemia

Compensatory changes in the hippocampus of somatostatin knockout mice: upregulation of somatostatin receptor 2 and its function in the control of bursting activity and synaptic transmission

Somatostatin: An endogenous antiepileptic

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