Journal article
Reduced brain somatostatin in mood disorders: a common pathophysiological substrate and drug target?
Frontiers in pharmacology, Vol.4, pp.110-110
09/09/2013
DOI: 10.3389/fphar.2013.00110
PMCID: PMC3766825
PMID: 24058344
Abstract
Our knowledge of the pathophysiology of affect dysregulation has progressively increased, but the pharmacological treatments remain inadequate. Here, we summarize the current literature on deficits in somatostatin, an inhibitory modulatory neuropeptide, in major depression and other neurological disorders that also include mood disturbances. We focus on direct evidence in the human postmortem brain, and review rodent genetic and pharmacological studies probing the role of the somatostatin system in relation to mood. We also briefly go over pharmacological developments targeting the somatostatin system in peripheral organs and discuss the challenges of targeting the brain somatostatin system. Finally, the fact that somatostatin deficits are frequently observed across neurological disorders suggests a selective cellular vulnerability of somatostatin-expressing neurons. Potential cell intrinsic factors mediating those changes are discussed, including nitric oxide induced oxidative stress, mitochondrial dysfunction, high inflammatory response, high demand for neurotrophic environment, and overall aging processes. Together, based on the co-localization of somatostatin with gamma-aminobutyric acid (GABA), its presence in dendritic-targeting GABA neuron subtypes, and its temporal-specific function, we discuss the possibility that deficits in somatostatin play a central role in cortical local inhibitory circuit deficits leading to abnormal corticolimbic network activity and clinical mood symptoms across neurological disorders.
Details
- Title: Subtitle
- Reduced brain somatostatin in mood disorders: a common pathophysiological substrate and drug target?
- Creators
- Li-Chun Lin - University of PittsburghEtienne Sibille - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Frontiers in pharmacology, Vol.4, pp.110-110
- DOI
- 10.3389/fphar.2013.00110
- PMID
- 24058344
- PMCID
- PMC3766825
- NLM abbreviation
- Front Pharmacol
- ISSN
- 1663-9812
- eISSN
- 1663-9812
- Grant note
- R01 MH077159 / NIMH NIH HHS R01 MH093723 / NIMH NIH HHS K02 MH084060 / NIMH NIH HHS
- Language
- English
- Date published
- 09/09/2013
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984184143402771
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