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

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Psychiatry

Background:

• Neurexin 1 (NRXN1) is a presynaptic cell adhesion molecule linked to neurodevelopmental disorders.
• Synaptic dysfunction is a hallmark of conditions such as autism, intellectual disability, and schizophrenia.
• Understanding NRXN1's role in human cortical development is crucial for elucidating these disorders.

Purpose of the Study:

• To examine the expression patterns of NRXN1 and its isoforms (NRXN1-α, NRXN1-β) in the human prefrontal cortex across development.
• To investigate alterations in NRXN1 transcript levels in individuals with schizophrenia and bipolar disorder compared to controls.

Main Methods:

• Quantitative real-time PCR was employed to analyze NRXN1 transcript expression.
• Samples were obtained from human prefrontal cortex across fetal stages, postnatal development, and aging.
• Expression levels were compared between patients with schizophrenia or bipolar disorder and non-psychiatric controls.

Main Results:

• NRXN1 transcripts showed high expression during fetal cortical development, increasing with gestational age.
• Postnatally, NRXN1 levels peaked at birth, declining to stable levels by early childhood.
• NRXN1-β was elevated in schizophrenia, while NRXN1-α was increased in bipolar disorder.

Conclusions:

• NRXN1 expression is highest in the dorsolateral prefrontal cortex during critical neurodevelopmental periods.
• These findings highlight NRXN1's potential involvement in the etiology of neurodevelopmental disorders.
• Differential alterations in NRXN1 expression may contribute to the pathophysiology of neuropsychiatric disorders.