Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

Abstract

Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1−/− mice exhibited behavioral abnormalities related to schizophrenia. The crmp1−/− mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1−/− mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1−/− mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1−/− mouse may model endophenotypes present in this neuropsychiatric disorder.

Blocking CRMP2 SUMOylation reverses neuropathic pain

“…3 Mice lacking CRMP1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition behavioral abnormalities related to schizophrenia. 4 Genetic association and linkage studies pointed to CRMP2 as a liability gene for schizophrenia, autism, alcohol dependence, depression and bipolar disorders. 5–10 Mice with brain-specific Crmp2 deletion exhibited behavioral deficits in locomotor activity, sensorimotor gating, social behavior, and spatial learning and memory.…”

CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury

“…In Crmp1−/− mice, a decrease in granule cell proliferation and apoptosis in the developing cerebellum [45], a series of schizophrenia-like behavioral abnormalities, impaired learning and memory, and structural changes to the neurites of cortical and hippocampal neurons [46][47][48] were observed. Additionally, CRMP1 is also involved with neuronal migration, where Fyn activation by Reelin stimulation, along with Dab1, causes the Tyr phosphorylation of CRMP1, controlling cortical migration [49].…”

“…For information on the relationship between CRMPs and Alzheimer's disease (AD), neuropsychiatric disease, and epilepsy, see other reviews [10,11]. Crmp1-/-Decrease in granule cell proliferation and apoptosis [45] Schizophrenia-like phenotype [47] Retarded neuronal migration [49] Disorientation of apical dendrites and impaired dendritic spine density [48] Impaired learning and memory [46,47] CRMP2…”

Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb

“…; Yamashita et al. ). CRMP2 gene polymorphism and altered expression levels of CRMP1 or CRMP2 have been reported in schizophrenia (Edgar et al.…”