Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging

• Published in: Molecular psychiatry Vol. 21; no. 5; pp. 701 - 706
• Main Authors: Jenkins, A K, Paterson, C, Wang, Y, Hyde, T M, Kleinman, J E, Law, A J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2016; Nature Publishing Group
• Subjects: 38; 38/39; 631/208; 631/337; 631/378; 692/699/476/1799; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Aging - metabolism; Autism; Behavioral Sciences; Biological Psychology; Bipolar disorder; Bipolar Disorder - metabolism; Brain; Calcium-Binding Proteins; Cell adhesion & migration; Cell adhesion molecules; Cell Adhesion Molecules, Neuronal - metabolism; Child; Child, Preschool; Developmental biology; Female; Fetuses; Gene expression; Gestational age; Humans; Infant; Infant, Newborn; Intellectual disabilities; Isoforms; Life span; Male; Medical examination; Medicine; Medicine & Public Health; Mental disorders; Mental health; Middle Aged; Neocortex - growth & development; Neocortex - metabolism; Nerve Tissue Proteins - metabolism; Nervous system; Neural Cell Adhesion Molecules; Neurodevelopmental disorders; Neurosciences; Observations; original-article; Pharmacotherapy; Polymerase chain reaction; Prefrontal cortex; Properties; Protein Isoforms; Proteins; Psychiatry; Review boards; Schizophrenia; Schizophrenia - metabolism; Young Adult; United States > US; Baltimore Maryland
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2015.107

Neurexin 1 (NRXN1), a presynaptic cell adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including autism, intellectual disability and schizophrenia. To gain insight into NRXN1’s involvement in human cortical development we used quantitative real-time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms, NRXN1-α and NRXN1-β, in prefrontal cortex from fetal stages to aging. In addition, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison with non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, markedly increasing with gestational age. In the postnatal dorsolateral prefrontal cortex, expression levels were negatively correlated with age, peaking at birth until ~3 years of age, after which levels declined markedly to be stable across the lifespan. NRXN1-β expression was modestly but significantly elevated in the brains of patients with schizophrenia compared with non-psychiatric controls, whereas NRXN1-α expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human dorsolateral prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders.