Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model
Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by deficits in social skills, abnormal sensory responses and a loss of neuronal cells. A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of...
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description | Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by deficits in social skills, abnormal sensory responses and a loss of neuronal cells. A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of this study was to measure the levels of γ-aminobutyric acid (GABA), glutamate (GLU) and serotonin (5-HT) in the thalamus of a rat valproic acid (VPA)-induced ASD model and to correlate these levels with the number of thalamic cells. Ten pregnant Wistar rats were injected with 600 mg/kg VPA on Day 12.5 of gestation, whereas five control rats received saline. After the behavioral tests, the male pups were divided into ASD and control groups with ten animals each. At 55 days of age, pups underwent microdialysis under anesthesia, and thalamic samples were analyzed for GABA, GLU and 5-HT levels by ultrahigh-performance liquid chromatography (UHPLC). After microdialysis, the brain sections were stained, and the volumes of the thalamus and hemispheres were calculated using the Cavalieri method, with the number of neurons and glia determined using the optical fractionator method. Compared with the control group, the ASD group presented increased 5-HT levels, an increased hemispheric volume, a decreased thalamic volume and decreased numbers of thalamic neurons and glia. A negative correlation was observed between the GLU content and glial number in the control group but not in the ASD group. These results indicate a disturbed thalamic neurotransmitter balance. We suggest that the increased thalamic 5-HT levels in ASD rats indicates that 5-HT reuptake is inhibited by the GLU content, which remains unchanged, despite the reduced cell number. |
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A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of this study was to measure the levels of γ-aminobutyric acid (GABA), glutamate (GLU) and serotonin (5-HT) in the thalamus of a rat valproic acid (VPA)-induced ASD model and to correlate these levels with the number of thalamic cells. Ten pregnant Wistar rats were injected with 600 mg/kg VPA on Day 12.5 of gestation, whereas five control rats received saline. After the behavioral tests, the male pups were divided into ASD and control groups with ten animals each. At 55 days of age, pups underwent microdialysis under anesthesia, and thalamic samples were analyzed for GABA, GLU and 5-HT levels by ultrahigh-performance liquid chromatography (UHPLC). After microdialysis, the brain sections were stained, and the volumes of the thalamus and hemispheres were calculated using the Cavalieri method, with the number of neurons and glia determined using the optical fractionator method. Compared with the control group, the ASD group presented increased 5-HT levels, an increased hemispheric volume, a decreased thalamic volume and decreased numbers of thalamic neurons and glia. A negative correlation was observed between the GLU content and glial number in the control group but not in the ASD group. These results indicate a disturbed thalamic neurotransmitter balance. We suggest that the increased thalamic 5-HT levels in ASD rats indicates that 5-HT reuptake is inhibited by the GLU content, which remains unchanged, despite the reduced cell number.</description><identifier>ISSN: 0364-3190</identifier><identifier>ISSN: 1573-6903</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-024-04299-2</identifier><identifier>PMID: 39636522</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Anesthesia ; Animal models ; Animals ; Autism ; Autism Spectrum Disorder - chemically induced ; Autism Spectrum Disorder - metabolism ; Autistic Disorder - chemically induced ; Autistic Disorder - metabolism ; Autistic Disorder - pathology ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Cell Count ; Cell number ; Cerebral hemispheres ; Disease Models, Animal ; Disorders ; Female ; gamma-Aminobutyric Acid - metabolism ; Glutamic Acid - metabolism ; Hemispheres ; Juveniles ; Liquid chromatography ; Male ; Microdialysis ; Neurochemistry ; Neurodevelopmental disorders ; Neurology ; Neuronal-glial interactions ; Neurons ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; Neurosciences ; Pregnancy ; Rats ; Rats, Wistar ; Sensory evaluation ; Serotonin ; Serotonin - metabolism ; Thalamus ; Thalamus - drug effects ; Thalamus - metabolism ; Thalamus - pathology ; Valproic Acid ; γ-Aminobutyric acid</subject><ispartof>Neurochemical research, 2025-02, Vol.50 (1), p.45, Article 45</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>Copyright Springer Nature B.V. 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A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of this study was to measure the levels of γ-aminobutyric acid (GABA), glutamate (GLU) and serotonin (5-HT) in the thalamus of a rat valproic acid (VPA)-induced ASD model and to correlate these levels with the number of thalamic cells. Ten pregnant Wistar rats were injected with 600 mg/kg VPA on Day 12.5 of gestation, whereas five control rats received saline. After the behavioral tests, the male pups were divided into ASD and control groups with ten animals each. At 55 days of age, pups underwent microdialysis under anesthesia, and thalamic samples were analyzed for GABA, GLU and 5-HT levels by ultrahigh-performance liquid chromatography (UHPLC). After microdialysis, the brain sections were stained, and the volumes of the thalamus and hemispheres were calculated using the Cavalieri method, with the number of neurons and glia determined using the optical fractionator method. Compared with the control group, the ASD group presented increased 5-HT levels, an increased hemispheric volume, a decreased thalamic volume and decreased numbers of thalamic neurons and glia. A negative correlation was observed between the GLU content and glial number in the control group but not in the ASD group. These results indicate a disturbed thalamic neurotransmitter balance. We suggest that the increased thalamic 5-HT levels in ASD rats indicates that 5-HT reuptake is inhibited by the GLU content, which remains unchanged, despite the reduced cell number.</description><subject>Anesthesia</subject><subject>Animal models</subject><subject>Animals</subject><subject>Autism</subject><subject>Autism Spectrum Disorder - chemically induced</subject><subject>Autism Spectrum Disorder - metabolism</subject><subject>Autistic Disorder - chemically induced</subject><subject>Autistic Disorder - metabolism</subject><subject>Autistic Disorder - pathology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cell Count</subject><subject>Cell number</subject><subject>Cerebral hemispheres</subject><subject>Disease Models, Animal</subject><subject>Disorders</subject><subject>Female</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Glutamic Acid - metabolism</subject><subject>Hemispheres</subject><subject>Juveniles</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Microdialysis</subject><subject>Neurochemistry</subject><subject>Neurodevelopmental disorders</subject><subject>Neurology</subject><subject>Neuronal-glial interactions</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neurosciences</subject><subject>Pregnancy</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sensory evaluation</subject><subject>Serotonin</subject><subject>Serotonin - metabolism</subject><subject>Thalamus</subject><subject>Thalamus - drug effects</subject><subject>Thalamus - metabolism</subject><subject>Thalamus - pathology</subject><subject>Valproic Acid</subject><subject>γ-Aminobutyric acid</subject><issn>0364-3190</issn><issn>1573-6903</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhi0EokPhBVggS2zYBHzPeBkGGEaaggQt28i3UFdOMtgJUp-HF-XMpAWJBQsrks_3_T7Kj9BzSl5TQuo3hVKiREUYHMG0rtgDtKKy5pXShD9EK8JhzKkmZ-hJKTeEgMboY3TGteJKMrZCv3aDy8GU4PHXkMdpHOKA9-FnSAWbweOrwV2b4TuMt2meTG-mcLrfNm-bew6My2uTTB8dvogujz6adFsALfhdKIcIzpfgZwcpm5AS_jT3NuSTaPA3kw55BLVx0Ve7YeGaeYqlxxejD-kpetSZVMKzu-85uvrw_nLzsdp_3u42zb5yTKqpcnUnqaW681b4daBcW09Ex2nt67WyNbPKUm67zknJNffSC-00Ex1lhgYl-Dl6teTCPj_mUKa2j8XBwmYI41xaToWSnAiyBvTlP-jNOOcBtjtSlEkhagYUWyj4J6Xk0LWHHHuTb1tK2mOF7VJhCxW2pwrbo_TiLnq2ffB_lPvOAOALUGAE1eS_b_8n9jfN5adD</recordid><startdate>20250201</startdate><enddate>20250201</enddate><creator>Ay, Hakan</creator><creator>Horata, Erdal</creator><creator>Öncü Kaya, Elif Mine</creator><creator>Korkmaz, Orhan Tansel</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1359-228X</orcidid><orcidid>https://orcid.org/0000-0002-0423-7000</orcidid><orcidid>https://orcid.org/0000-0003-4638-0750</orcidid><orcidid>https://orcid.org/0000-0003-1410-740X</orcidid></search><sort><creationdate>20250201</creationdate><title>Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model</title><author>Ay, Hakan ; Horata, Erdal ; Öncü Kaya, Elif Mine ; Korkmaz, Orhan Tansel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-c7f51b19fdb4d8e139bd04f317d786b72b6b13bffc55393d5d49c924f12a1e643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Anesthesia</topic><topic>Animal models</topic><topic>Animals</topic><topic>Autism</topic><topic>Autism Spectrum Disorder - chemically induced</topic><topic>Autism Spectrum Disorder - metabolism</topic><topic>Autistic Disorder - chemically induced</topic><topic>Autistic Disorder - metabolism</topic><topic>Autistic Disorder - pathology</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Cell Count</topic><topic>Cell number</topic><topic>Cerebral hemispheres</topic><topic>Disease Models, Animal</topic><topic>Disorders</topic><topic>Female</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Glutamic Acid - metabolism</topic><topic>Hemispheres</topic><topic>Juveniles</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Microdialysis</topic><topic>Neurochemistry</topic><topic>Neurodevelopmental disorders</topic><topic>Neurology</topic><topic>Neuronal-glial interactions</topic><topic>Neurons</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neurosciences</topic><topic>Pregnancy</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sensory evaluation</topic><topic>Serotonin</topic><topic>Serotonin - metabolism</topic><topic>Thalamus</topic><topic>Thalamus - drug effects</topic><topic>Thalamus - metabolism</topic><topic>Thalamus - pathology</topic><topic>Valproic Acid</topic><topic>γ-Aminobutyric acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ay, Hakan</creatorcontrib><creatorcontrib>Horata, Erdal</creatorcontrib><creatorcontrib>Öncü Kaya, Elif Mine</creatorcontrib><creatorcontrib>Korkmaz, Orhan Tansel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ay, Hakan</au><au>Horata, Erdal</au><au>Öncü Kaya, Elif Mine</au><au>Korkmaz, Orhan Tansel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2025-02-01</date><risdate>2025</risdate><volume>50</volume><issue>1</issue><spage>45</spage><pages>45-</pages><artnum>45</artnum><issn>0364-3190</issn><issn>1573-6903</issn><eissn>1573-6903</eissn><abstract>Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by deficits in social skills, abnormal sensory responses and a loss of neuronal cells. A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of this study was to measure the levels of γ-aminobutyric acid (GABA), glutamate (GLU) and serotonin (5-HT) in the thalamus of a rat valproic acid (VPA)-induced ASD model and to correlate these levels with the number of thalamic cells. Ten pregnant Wistar rats were injected with 600 mg/kg VPA on Day 12.5 of gestation, whereas five control rats received saline. After the behavioral tests, the male pups were divided into ASD and control groups with ten animals each. At 55 days of age, pups underwent microdialysis under anesthesia, and thalamic samples were analyzed for GABA, GLU and 5-HT levels by ultrahigh-performance liquid chromatography (UHPLC). After microdialysis, the brain sections were stained, and the volumes of the thalamus and hemispheres were calculated using the Cavalieri method, with the number of neurons and glia determined using the optical fractionator method. Compared with the control group, the ASD group presented increased 5-HT levels, an increased hemispheric volume, a decreased thalamic volume and decreased numbers of thalamic neurons and glia. A negative correlation was observed between the GLU content and glial number in the control group but not in the ASD group. These results indicate a disturbed thalamic neurotransmitter balance. We suggest that the increased thalamic 5-HT levels in ASD rats indicates that 5-HT reuptake is inhibited by the GLU content, which remains unchanged, despite the reduced cell number.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>39636522</pmid><doi>10.1007/s11064-024-04299-2</doi><orcidid>https://orcid.org/0000-0003-1359-228X</orcidid><orcidid>https://orcid.org/0000-0002-0423-7000</orcidid><orcidid>https://orcid.org/0000-0003-4638-0750</orcidid><orcidid>https://orcid.org/0000-0003-1410-740X</orcidid></addata></record> |
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subjects | Anesthesia Animal models Animals Autism Autism Spectrum Disorder - chemically induced Autism Spectrum Disorder - metabolism Autistic Disorder - chemically induced Autistic Disorder - metabolism Autistic Disorder - pathology Biochemistry Biomedical and Life Sciences Biomedicine Cell Biology Cell Count Cell number Cerebral hemispheres Disease Models, Animal Disorders Female gamma-Aminobutyric Acid - metabolism Glutamic Acid - metabolism Hemispheres Juveniles Liquid chromatography Male Microdialysis Neurochemistry Neurodevelopmental disorders Neurology Neuronal-glial interactions Neurons Neurons - drug effects Neurons - metabolism Neurons - pathology Neurosciences Pregnancy Rats Rats, Wistar Sensory evaluation Serotonin Serotonin - metabolism Thalamus Thalamus - drug effects Thalamus - metabolism Thalamus - pathology Valproic Acid γ-Aminobutyric acid |
title | Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model |
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