{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T07:25:06Z","timestamp":1762759506227,"version":"build-2065373602"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biochem Genet"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s10528-024-11004-z","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:59:14Z","timestamp":1735174754000},"page":"5613-5625","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased GABBR2 Expression on Cell Membranes Causes Increased Ca2\u2009+\u2009Inward Flow, Associated with Cognitive Impairment in Early Alzheimer\u2019s Disease"],"prefix":"10.1007","volume":"63","author":[{"given":"Yifei","family":"Weng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guomin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"issue":"4","key":"11004_CR1","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1002\/alz.13016","volume":"19","author":"Alzheimer\u2019s disease facts and figures","year":"2023","unstructured":"Alzheimer\u2019s disease facts and figures (2023) Alzheimer\u2019s Dementia 19(4):1598\u20131695. https:\/\/doi.org\/10.1002\/alz.13016","journal-title":"Alzheimer\u2019s Dementia"},{"key":"11004_CR2","doi-asserted-by":"publisher","first-page":"1267343","DOI":"10.3389\/fnmol.2023.1267343","volume":"16","author":"N Bielopolski","year":"2023","unstructured":"Bielopolski N, Stawarski M, Roitman I, Fridman K, Wald-Altman S, Fr\u00fch S et al (2023) Characterization of a de novo GABBR2 variant linked to autism spectrum disorder. Front Mol Neurosci 16:1267343. https:\/\/doi.org\/10.3389\/fnmol.2023.1267343","journal-title":"Front Mol Neurosci"},{"issue":"1","key":"11004_CR3","doi-asserted-by":"publisher","first-page":"a038802","DOI":"10.1101\/cshperspect.a038802","volume":"12","author":"MD Bootman","year":"2020","unstructured":"Bootman MD, Bultynck G (2020) Fundamentals of cellular calcium signaling: a primer. Cold Spring Harbor Perspectives in Biol 12(1):a038802. https:\/\/doi.org\/10.1101\/cshperspect.a038802","journal-title":"Cold Spring Harbor Perspectives in Biol"},{"issue":"15","key":"11004_CR4","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1007\/s00018-013-1550-7","volume":"71","author":"M Brini","year":"2014","unstructured":"Brini M, Cal\u00ec T, Ottolini D, Carafoli E (2014) Neuronal calcium signaling: function and dysfunction. Cell Mol Life Sci 71(15):2787\u20132814. https:\/\/doi.org\/10.1007\/s00018-013-1550-7","journal-title":"Cell Mol Life Sci"},{"issue":"4","key":"11004_CR5","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3233\/jad-160726","volume":"57","author":"Q Cai","year":"2017","unstructured":"Cai Q, Tammineni P (2017) Mitochondrial aspects of synaptic dysfunction in Alzheimer\u2019s disease. J Alzheimer\u2019s Disease 57(4):1087\u20131103. https:\/\/doi.org\/10.3233\/jad-160726","journal-title":"J Alzheimer\u2019s Disease"},{"issue":"1","key":"11004_CR6","doi-asserted-by":"publisher","first-page":"93","DOI":"10.9758\/cpn.2020.18.1.93","volume":"18","author":"MR Choi","year":"2020","unstructured":"Choi MR, Jin YB, Bang SH, Im CN, Lee Y, Kim HN et al (2020) Age-related effects of heroin on gene expression in the hippocampus and striatum of cynomolgus monkeys. Clin Psychopharmacol Neurosci 18(1):93\u2013108. https:\/\/doi.org\/10.9758\/cpn.2020.18.1.93","journal-title":"Clin Psychopharmacol Neurosci"},{"issue":"1","key":"11004_CR7","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s43440-023-00563-4","volume":"76","author":"A Cieslik-Starkiewicz","year":"2024","unstructured":"Cieslik-Starkiewicz A, Noworyta K, Solich J, Korlatowicz A, Faron-G\u00f3recka A, Rygula R (2024) Identification of genes regulated by trait sensitivity to negative feedback and prolonged alcohol consumption in rats. Pharmacol Rep 76(1):207\u2013215. https:\/\/doi.org\/10.1007\/s43440-023-00563-4","journal-title":"Pharmacol Rep"},{"key":"11004_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/cells11172728","author":"G Di Benedetto","year":"2022","unstructured":"Di Benedetto G, Burgaletto C, Bellanca CM, Munaf\u00f2 A, Bernardini R, Cantarella G (2022) Role of microglia and astrocytes in Alzheimer\u2019s disease: from neuroinflammation to Ca(2+) homeostasis dysregulation. Cells. https:\/\/doi.org\/10.3390\/cells11172728","journal-title":"Cells"},{"issue":"1\u20133","key":"11004_CR9","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.schres.2010.12.025","volume":"128","author":"SH Fatemi","year":"2011","unstructured":"Fatemi SH, Folsom TD, Thuras PD (2011) Deficits in GABA(B) receptor system in schizophrenia and mood disorders: a postmortem study. Schizophr Res 128(1\u20133):37\u201343. https:\/\/doi.org\/10.1016\/j.schres.2010.12.025","journal-title":"Schizophr Res"},{"issue":"9","key":"11004_CR10","doi-asserted-by":"publisher","first-page":"e303","DOI":"10.1038\/tp.2013.64","volume":"3","author":"SH Fatemi","year":"2013","unstructured":"Fatemi SH, Folsom TD, Rooney RJ, Thuras PD (2013) Expression of GABAA \u03b12-, \u03b21- and \u03b5-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Transl Psychiatry 3(9):e303. https:\/\/doi.org\/10.1038\/tp.2013.64","journal-title":"Transl Psychiatry"},{"key":"11004_CR11","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.seizure.2022.07.007","volume":"101","author":"Y Feng","year":"2022","unstructured":"Feng Y, Wei ZH, Liu C, Li GY, Qiao XZ, Gan YJ et al (2022) Genetic variations in GABA metabolism and epilepsy. Seizure 101:22\u201329. https:\/\/doi.org\/10.1016\/j.seizure.2022.07.007","journal-title":"Seizure"},{"issue":"2","key":"11004_CR12","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/alz.12694","volume":"19","author":"A Gustavsson","year":"2023","unstructured":"Gustavsson A, Norton N, Fast T, Fr\u00f6lich L, Georges J, Holzapfel D et al (2023) Global estimates on the number of persons across the Alzheimer\u2019s disease continuum. Alzheimer\u2019s Dementia 19(2):658\u2013670. https:\/\/doi.org\/10.1002\/alz.12694","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"5054","key":"11004_CR13","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1126\/science.1566067","volume":"256","author":"JA Hardy","year":"1992","unstructured":"Hardy JA, Higgins GA (1992) Alzheimer\u2019s disease: the amyloid cascade hypothesis. Science (New York, NY) 256(5054):184\u2013185. https:\/\/doi.org\/10.1126\/science.1566067","journal-title":"Science (New York, NY)"},{"key":"11004_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.1994.tb44398.x","volume":"747","author":"ZS Khachaturian","year":"1994","unstructured":"Khachaturian ZS (1994) Calcium hypothesis of Alzheimer\u2019s disease and brain aging. Ann N Y Acad Sci 747:1\u201311. https:\/\/doi.org\/10.1111\/j.1749-6632.1994.tb44398.x","journal-title":"Ann N Y Acad Sci"},{"issue":"2","key":"11004_CR15","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.neuron.2008.06.008","volume":"59","author":"KV Kuchibhotla","year":"2008","unstructured":"Kuchibhotla KV, Goldman ST, Lattarulo CR, Wu HY, Hyman BT, Bacskai BJ (2008) Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 59(2):214\u2013225. https:\/\/doi.org\/10.1016\/j.neuron.2008.06.008","journal-title":"Neuron"},{"key":"11004_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biosystems.2015.05.003","volume":"134","author":"J Liang","year":"2015","unstructured":"Liang J, Kulasiri D, Samarasinghe S (2015) Ca2+ dysregulation in the endoplasmic reticulum related to Alzheimer\u2019s disease: a review on experimental progress and computational modeling. Biosystems 134:1\u201315. https:\/\/doi.org\/10.1016\/j.biosystems.2015.05.003","journal-title":"Biosystems"},{"issue":"1","key":"11004_CR17","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/j.1471-4159.2007.05135.x","volume":"105","author":"JR Lopez","year":"2008","unstructured":"Lopez JR, Lyckman A, Oddo S, Laferla FM, Querfurth HW, Shtifman A (2008) Increased intraneuronal resting [Ca2+] in adult Alzheimer\u2019s disease mice. J Neurochem 105(1):262\u2013271. https:\/\/doi.org\/10.1111\/j.1471-4159.2007.05135.x","journal-title":"J Neurochem"},{"issue":"3","key":"11004_CR18","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1007\/s11033-021-07019-z","volume":"49","author":"A Miyazawa","year":"2022","unstructured":"Miyazawa A, Kanahara N, Kogure M, Otsuka I, Okazaki S, Watanabe Y et al (2022) A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia. Mol Biol Rep 49(3):2015\u20132024. https:\/\/doi.org\/10.1007\/s11033-021-07019-z","journal-title":"Mol Biol Rep"},{"issue":"19\u201320","key":"11004_CR19","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1016\/s0024-3205(01)01018-9","volume":"68","author":"H M\u00f6hler","year":"2001","unstructured":"M\u00f6hler H, Benke D, Fritschy JM (2001) GABA(B)-receptor isoforms molecular architecture and distribution. Life Sci 68(19\u201320):2297\u20132300. https:\/\/doi.org\/10.1016\/s0024-3205(01)01018-9","journal-title":"Life Sci"},{"key":"11004_CR20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s40478-014-0135-5","volume":"2","author":"GP Morris","year":"2014","unstructured":"Morris GP, Clark IA, Vissel B (2014) Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer\u2019s disease. Acta Neuropathol Commun 2:135. https:\/\/doi.org\/10.1186\/s40478-014-0135-5","journal-title":"Acta Neuropathol Commun"},{"issue":"7","key":"11004_CR21","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1089\/ars.2010.3421","volume":"14","author":"M M\u00fcller","year":"2011","unstructured":"M\u00fcller M, Cheung KH, Foskett JK (2011) Enhanced ROS generation mediated by Alzheimer\u2019s disease presenilin regulation of InsP3R Ca2+ signaling. Antioxid Redox Signal 14(7):1225\u20131235. https:\/\/doi.org\/10.1089\/ars.2010.3421","journal-title":"Antioxid Redox Signal"},{"issue":"46","key":"11004_CR22","doi-asserted-by":"publisher","first-page":"44148","DOI":"10.1021\/acsomega.3c06448","volume":"8","author":"YC Odabasi","year":"2023","unstructured":"Odabasi YC, Yanasik S, Saglam-Metiner P, Kaymaz Y, Yesil-Celiktas O (2023) Comprehensive transcriptomic investigation of rett syndrome reveals increasing complexity trends from induced pluripotent stem cells to neurons with implications for enriched pathways. ACS Omega 8(46):44148\u201344162. https:\/\/doi.org\/10.1021\/acsomega.3c06448","journal-title":"ACS Omega"},{"issue":"15","key":"11004_CR23","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1016\/j.febslet.2010.07.014","volume":"584","author":"HW Park","year":"2010","unstructured":"Park HW, Jung H, Choi KH, Baik JH, Rhim H (2010) Direct interaction and functional coupling between voltage-gated CaV1.3 Ca2+ channel and GABAB receptor subunit 2. FEBS Lett 584(15):3317\u20133322. https:\/\/doi.org\/10.1016\/j.febslet.2010.07.014","journal-title":"FEBS Lett"},{"key":"11004_CR24","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaz0961","author":"JB Parys","year":"2019","unstructured":"Parys JB, Guse AH (2019) Full focus on calcium. Sci Signal. https:\/\/doi.org\/10.1126\/scisignal.aaz0961","journal-title":"Sci Signal"},{"issue":"1\u20132","key":"11004_CR25","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.gene.2011.08.031","volume":"490","author":"PN Plummer","year":"2011","unstructured":"Plummer PN, Colson NJ, Lewohl JM, MacKay RK, Fernandez F, Haupt LM et al (2011) Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs. Gene 490(1\u20132):32\u201336. https:\/\/doi.org\/10.1016\/j.gene.2011.08.031","journal-title":"Gene"},{"issue":"1","key":"11004_CR26","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3390\/ijms24010107","volume":"24","author":"AA Rostagno","year":"2022","unstructured":"Rostagno AA (2022) Pathogenesis of Alzheimer\u2019s disease. Int J Mol Sci 24(1):107. https:\/\/doi.org\/10.3390\/ijms24010107","journal-title":"Int J Mol Sci"},{"key":"11004_CR27","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3389\/fnagi.2019.00186","volume":"11","author":"NR Smalheiser","year":"2019","unstructured":"Smalheiser NR (2019) Ketamine: a neglected therapy for alzheimer disease. Front Aging Neurosci 11:186. https:\/\/doi.org\/10.3389\/fnagi.2019.00186","journal-title":"Front Aging Neurosci"},{"issue":"27","key":"11004_CR28","doi-asserted-by":"publisher","first-page":"E2518","DOI":"10.1073\/pnas.1306832110","volume":"110","author":"M Talantova","year":"2013","unstructured":"Talantova M, Sanz-Blasco S, Zhang X, Xia P, Akhtar MW, Okamoto S et al (2013) A\u03b2 induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proc Natl Acad Sci USA 110(27):E2518\u2013E2527. https:\/\/doi.org\/10.1073\/pnas.1306832110","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"11004_CR29","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3233\/jad-220683","volume":"92","author":"R Tandon","year":"2023","unstructured":"Tandon R, Levey AI, Lah JJ, Seyfried NT, Mitchell CS (2023) Machine learning selection of most predictive brain proteins suggests role of sugar metabolism in Alzheimer\u2019s disease. J Alzheimer\u2019s Disease 92(2):411\u2013424. https:\/\/doi.org\/10.3233\/jad-220683","journal-title":"J Alzheimer\u2019s Disease"},{"key":"11004_CR30","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2147\/cia.s6666","volume":"4","author":"SJ Thomas","year":"2009","unstructured":"Thomas SJ, Grossberg GT (2009) Memantine: a review of studies into its safety and efficacy in treating Alzheimer\u2019s disease and other dementias. Clin Interv Aging 4:367\u2013377. https:\/\/doi.org\/10.2147\/cia.s6666","journal-title":"Clin Interv Aging"},{"issue":"7","key":"11004_CR31","doi-asserted-by":"publisher","first-page":"6518","DOI":"10.3390\/ijms24076518","volume":"24","author":"B Twarowski","year":"2023","unstructured":"Twarowski B, Herbet M (2023) Inflammatory processes in Alzheimer\u2019s disease\u2014pathomechanism, diagnosis and treatment: a review. Int J Mol Sci 24(7):6518. https:\/\/doi.org\/10.3390\/ijms24076518","journal-title":"Int J Mol Sci"},{"issue":"2","key":"11004_CR32","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s00380-014-0499-2","volume":"30","author":"XP Wang","year":"2015","unstructured":"Wang XP, Cheng ZY, Schmid KL (2015) GABAB receptors are expressed in human aortic smooth muscle cells and regulate the intracellular Ca(2+) concentration. Heart Vessels 30(2):249\u2013257. https:\/\/doi.org\/10.1007\/s00380-014-0499-2","journal-title":"Heart Vessels"},{"key":"11004_CR33","doi-asserted-by":"publisher","first-page":"110830","DOI":"10.1016\/j.brainresbull.2023.110830","volume":"205","author":"E Wei","year":"2023","unstructured":"Wei E, Gao A, Mu X, Qu S, Yang C, Li F et al (2023) Paeonol ameliorates hippocampal neuronal damage by inhibiting GRM5\/GABBR2\/\u03b2-arrestin2 and activating the cAMP-PKA signaling pathway in premenstrual irritability rats. Brain Res Bull 205:110830. https:\/\/doi.org\/10.1016\/j.brainresbull.2023.110830","journal-title":"Brain Res Bull"},{"issue":"3","key":"11004_CR34","doi-asserted-by":"publisher","first-page":"e4936","DOI":"10.1371\/journal.pone.0004936","volume":"4","author":"C Williams","year":"2009","unstructured":"Williams C, Mehrian Shai R, Wu Y, Hsu YH, Sitzer T, Spann B et al (2009) Transcriptome analysis of synaptoneurosomes identifies neuroplasticity genes overexpressed in incipient Alzheimer\u2019s disease. PLoS ONE 4(3):e4936. https:\/\/doi.org\/10.1371\/journal.pone.0004936","journal-title":"PLoS ONE"},{"issue":"1","key":"11004_CR35","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3760\/cma.j.issn.0253-2727.2019.01.010","volume":"40","author":"J Wu","year":"2019","unstructured":"Wu J, Lu AD, Zhang LP, Zuo YX, Jia YP (2019) Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. 40(1):52\u201357. https:\/\/doi.org\/10.3760\/cma.j.issn.0253-2727.2019.01.010","journal-title":"Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi."},{"issue":"11","key":"11004_CR36","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1038\/mp.2014.156","volume":"20","author":"J Yang","year":"2015","unstructured":"Yang J, Wang S, Yang Z, Hodgkinson CA, Iarikova P, Ma JZ et al (2015) The contribution of rare and common variants in 30 genes to risk nicotine dependence. Mol Psychiatry 20(11):1467\u20131478. https:\/\/doi.org\/10.1038\/mp.2014.156","journal-title":"Mol Psychiatry"},{"issue":"34","key":"11004_CR37","doi-asserted-by":"publisher","first-page":"14670","DOI":"10.1073\/pnas.0903563106","volume":"106","author":"J Yao","year":"2009","unstructured":"Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD (2009) Mitochondrial bioenergetic deficit precedes Alzheimer\u2019s pathology in female mouse model of Alzheimer\u2019s disease. Proc Natl Acad Sci USA 106(34):14670\u201314675. https:\/\/doi.org\/10.1073\/pnas.0903563106","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Biochemical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10528-024-11004-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10528-024-11004-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10528-024-11004-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T07:20:42Z","timestamp":1762759242000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10528-024-11004-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,26]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["11004"],"URL":"https:\/\/doi.org\/10.1007\/s10528-024-11004-z","relation":{},"ISSN":["0006-2928","1573-4927"],"issn-type":[{"type":"print","value":"0006-2928"},{"type":"electronic","value":"1573-4927"}],"subject":[],"published":{"date-parts":[[2024,12,26]]},"assertion":[{"value":"2 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}