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Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs.
Ji, Jiatong; Chao, Honglu; Chen, Huimei; Liao, Jun; Shi, Wenqian; Ye, Yangfan; Wang, Tian; You, Yongping; Liu, Ning; Ji, Jing; Petretto, Enrico.
Afiliación
  • Ji J; Institute for Big Data and Artificial Intelligence in Medicine, School of Science, China Pharmaceutical University (CPU), Nanjing, Jiangsu 211198, People's Republic of China.
  • Chao H; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
  • Chen H; Institute for Big Data and Artificial Intelligence in Medicine, School of Science, China Pharmaceutical University (CPU), Nanjing, Jiangsu 211198, People's Republic of China.
  • Liao J; Duke-NUS Medical School, Singapore 169857, Singapore.
  • Shi W; High Performance Computing Center, School of Science, China Pharmaceutical University (CPU), Nanjing, Jiangsu 211198, People's Republic of China.
  • Ye Y; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
  • Wang T; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
  • You Y; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
  • Liu N; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
  • Ji J; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
  • Petretto E; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
Open Biol ; 14(6): 240063, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38864245
ABSTRACT
Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Psicotrópicos / Lóbulo Temporal / Lóbulo Frontal / Trastornos Mentales Límite: Humans Idioma: En Revista: Open Biol Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Psicotrópicos / Lóbulo Temporal / Lóbulo Frontal / Trastornos Mentales Límite: Humans Idioma: En Revista: Open Biol Año: 2024 Tipo del documento: Article
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