Work

Psychomotor disturbances in neuronal growth regulator-1-deficient (Negr1−/−) mice are associated with alterations in hippocampal and skeletal muscle signaling

Year: 2026

Type: article

Abstract: The motor domain has emerged as a fundamental transdiagnostic dimension of neuropsychiatric disorders, reflecting dysfunction in neural circuits underlying movement, cognition, and behavior. Neuronal growth regulator 1 (NEGR1) is a synaptic cell adhesion molecule genetically linked to multiple neuropsychiatric disorders. Despite its function in neural development and widespread expression in the central and peripheral nervous systems, its involvement in the motor domain remains unknown. Here, we investigated the motor domain by comprehensively characterizing psychomotor function and associated molecular alterations in adult male and female Negr1 −/− mice. Negr1 deficiency produced a motor phenotype characterized by altered run characteristics, gait dynamics, including swing speed, stride length and muscle strength, with molecular changes in the hippocampus and skeletal muscle. Male Negr1 −/− mice exhibited increased casein kinase 2 (CK2) activity in the hippocampus and skeletal muscle, whereas females showed reduced activity of CK2 and Rho-associated coiled-coil-containing protein kinase (ROCK) only in the hippocampus. Skeletal muscle further exhibited transcript-level alterations in genes encoding proteins involved in mitochondrial biology and contractility. Together, these findings indicate co-occurring central and peripheral molecular alterations underlying the multisystem psychomotor phenotype associated with Negr1 deficiency.

Source: Scientific Reports

DOI: 10.1038/s41598-026-77023-5