Occludin Deficiency is Associated with Developmental Impairment, Locomotor Dysfunction, and Social Deficiencies

Neurodevelopmental and psychiatric disorders, such as attention deficit hyperactivity disorder or autism spectrum disorder, have been intricately linked to structural impairments and compromised permeability of the blood-brain barrier (BBB). Occludin (ocln) is a tight junction (TJ) protein known for its role in maintaining BBB integrity. In the present manuscript, we report unexpected connection between ocln deficiency and behavioral alterations resembling neurodevelopmental and psychiatric disorders. Adolescent, occludin-deficient (ocln-/-) mice displayed an abnormal growth and neurological phenotype along with deterioration of motor functions as compared to wild-type controls. Moreover, adult ocln-/- mice exhibited increased hyperactivity, social difficulties, and attention deficits compared to control mice. Among the brain structures, the hippocampus appeared to be most susceptible to ocln deficiency as it exhibited higher expression levels of ocln than both the frontal cortex and striatum. Overall, the observed behavioral alteration patterns in ocln-/- mice indicated pronounced neurological motor dysfunction and behavioral changes that parallel those seen in attention deficit hyperactivity disorder and autism spectrum disorder. These findings are important for better understanding the role of ocln in neurodevelopmental and psychiatric disorders.