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      The role of neuropeptide somatostatin in the brain and its application in treating neurological disorders

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          Abstract

          Somatostatin (SST) is a well-known neuropeptide that is expressed throughout the brain. In the cortex, SST is expressed in a subset of GABAergic neurons and is known as a protein marker of inhibitory interneurons. Recent studies have identified the key functions of SST in modulating cortical circuits in the brain and cognitive function. Furthermore, reduced expression of SST is a hallmark of various neurological disorders, including Alzheimer’s disease and depression. In this review, we summarize the current knowledge on SST expression and function in the brain. In particular, we describe the physiological roles of SST-positive interneurons in the cortex. We further describe the causal relationship between pathophysiological changes in SST function and various neurological disorders, such as Alzheimer’s disease. Finally, we discuss potential treatments and possibility of novel drug developments for neurological disorders based on the current knowledge on the function of SST and SST analogs in the brain derived from experimental and clinical studies.

          Neuropeptide: Nerve cell protein may provide treatment options

          Developing stable analogues of a key neuronal protein and finding ways to deliver them directly to the brain may provide novel treatments for neurological disorders. The neuropeptide somatostatin (SST) is involved in regulating circuits in the brain cortex and maintaining cognitive function. Reduced SST expression is a recognised feature of brain disorders including Alzheimer’s disease. Seung-Hee Lee and co-workers at the Korea Advanced Institute of Science and Technology, Daejeon, South Korea, reviewed the role of SST and examined its therapeutic potential. SST deficiency appears to cause the significant memory loss found in Alzheimer’s, and there has been some success trialling intravenous injection of SST in patient trials. However, SST is short-lived in the body, limiting its usefulness as a treatment. Stable SST analogues and safe delivery methods could broaden treatment options for multiple brain conditions.

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          Shared and distinct transcriptomic cell types across neocortical areas

          The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.
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            How inhibition shapes cortical activity.

            Cortical processing reflects the interplay of synaptic excitation and synaptic inhibition. Rapidly accumulating evidence is highlighting the crucial role of inhibition in shaping spontaneous and sensory-evoked cortical activity and thus underscores how a better knowledge of inhibitory circuits is necessary for our understanding of cortical function. We discuss current views of how inhibition regulates the function of cortical neurons and point to a number of important open questions. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

              Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
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                Author and article information

                Contributors
                shlee1@kaist.ac.kr
                Journal
                Exp Mol Med
                Exp Mol Med
                Experimental & Molecular Medicine
                Nature Publishing Group UK (London )
                1226-3613
                2092-6413
                19 March 2021
                19 March 2021
                March 2021
                : 53
                : 3
                : 328-338
                Affiliations
                GRID grid.37172.30, ISNI 0000 0001 2292 0500, Department of Biological Sciences, , Korea Advanced Institute of Science and Technology, ; 291 Daehak-ro, Yuseong-gu, Daejeon 34141 Republic of Korea
                Author information
                http://orcid.org/0000-0002-9486-5771
                Article
                580
                10.1038/s12276-021-00580-4
                8080805
                33742131
                90e7ec9c-6bce-48f9-a0a5-2c813ad65201
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 December 2020
                : 23 January 2021
                : 25 January 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);
                Award ID: 2017R1A2B3008270
                Award ID: 2017M3C7A1030798
                Award ID: 2018R1A4A1025616
                Award ID: 2020R1I1A1A0107412511
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100007107, KAIST (Korea Advanced Institute of Science and Technology);
                Award ID: Global Singularity Program for 2020
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2021

                Molecular medicine
                molecular neuroscience,drug development
                Molecular medicine
                molecular neuroscience, drug development

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