{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BRINP1, a member of the BMP/RA‐inducible neural‐specific protein family, is highly expressed in multiple brain regions—including the hippocampus, cerebral cortex, and olfactory bulb—and plays an important role in neuronal differentiation and circuit formation. Studies in knockout mice have shown that loss of BRINP1 leads to deregulated neurogenesis in the dentate gyrus, an increase in immature neuronal populations, and altered interneuron distributions in the hippocampus and medial prefrontal cortex. These neuroanatomical changes are associated with behavioral abnormalities such as hyperactivity, reduced anxiety‐like behavior, impaired working memory, and poor social interaction, features that mirror aspects of several human psychiatric disorders (e.g., schizophrenia, autism spectrum disorder, and attention‐deficit/hyperactivity disorder)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, BRINP1 appears to function as a negative regulator of cell-cycle progression in post-mitotic neuronal cells. Its expression is controlled by epigenetic mechanisms—such as CpG island methylation—and by a neuron-restrictive silencing element (NRSE) in its promoter region, ensuring high expression in neural tissues and low expression in non-neural cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, genetic linkage studies have identified the BRINP1 locus among candidates associated with a high prevalence of major mental disorders in certain pedigrees, suggesting that variations in BRINP1 may contribute to neurodevelopmental abnormalities underlying psychiatric conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, BRINP1 functions to facilitate proper neuronal maturation by modulating cell-cycle arrest and promoting appropriate interneuron distribution. Its tightly regulated expression is critical for maintaining the balance between neurogenesis and neuronal differentiation, and disruptions in BRINP1 expression can lead to aberrant neural circuitry and behavioral phenotypes characteristic of several neuropsychiatric disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Miwako Kobayashi, Toshiyuki Nakatani, Toshiaki Koda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Brain (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1756-6606-7-12"}], "href": "https://doi.org/10.1186/1756-6606-7-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24528488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24528488"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Susan R Berkowicz, Travis J Featherby, Zhengdong Qu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Autism (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13229-016-0079-7"}], "href": "https://doi.org/10.1186/s13229-016-0079-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27042284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27042284"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Miwako Kobayashi, Yuichi Hayashi, Yuko Fujimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased parvalbumin and somatostatin neurons in medial prefrontal cortex in BRINP1-KO mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2018.06.050"}], "href": "https://doi.org/10.1016/j.neulet.2018.06.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29960053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29960053"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nakatani Toshiyuki, Matsuoka Ichiro "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanisms regulating cell type specific expression of BMP/RA Inducible Neural-specific Protein-1 that suppresses cell cycle progression: roles of NRSF/REST and DNA methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res Mol Brain Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molbrainres.2004.03.017"}], "href": "https://doi.org/10.1016/j.molbrainres.2004.03.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15193422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15193422"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Josep Pol-Fuster, Francesca Cañellas, Laura Ruiz-Guerra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The conserved ASTN2/BRINP1 locus at 9q33.1-33.2 is associated with major psychiatric disorders in a large pedigree from Southern Spain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-93555-4"}], "href": "https://doi.org/10.1038/s41598-021-93555-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34267256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34267256"}]}]}]}