{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that SREB2 (also known as GPR85), a highly conserved G protein‐coupled receptor, plays an essential role in brain development and function. Specifically, mild overexpression of SREB2 in transgenic mice leads to reduced brain weight, ventricular enlargement, and behavioral abnormalities—phenotypes that parallel features observed in psychiatric disorders such as schizophrenia. Genetic association studies further support a link between variations in the SREB2 gene and reduced hippocampal gray matter volume in patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have demonstrated that SREB2 functions as a negative regulator of adult hippocampal neurogenesis. In mouse models, overexpression of SREB2 decreases the proliferation and survival of newly generated cells in the dentate gyrus and impairs the dendritic development of newborn neurons, resulting in deficits in spatial discrimination and working memory. Conversely, knockout of SREB2 enhances neurogenesis and improves cognitive performance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary pharmacological studies have identified novel inverse agonists for SREB2 that modulate potassium channel opening in cerebellar Purkinje cells, suggesting that targeting this receptor may offer new therapeutic avenues for certain neurological disorders. These compounds, by adjusting the receptor’s constitutive activity, provide further insight into the neurochemical mechanisms influenced by SREB2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mitsuyuki Matsumoto, Richard E Straub, Stefano Marenco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0710717105"}], "href": "https://doi.org/10.1073/pnas.0710717105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18413613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18413613"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qian Chen, Jeffrey H Kogan, Adam K Gross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1460-9568.2012.08180.x"}], "href": "https://doi.org/10.1111/j.1460-9568.2012.08180.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22697179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22697179"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Aya Sakai, Takeshi Yasui, Masashi Watanave, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12931"}], "href": "https://doi.org/10.1111/gtc.12931"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35194900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35194900"}]}]}]}