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Loss of collapsin response mediator protein 4 suppresses dopaminergic neuron death in an 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced mouse model of Parkinson's disease
Author(s) -
Tonouchi Aine,
Nagai Jun,
Togashi Kentaro,
Goshima Yoshio,
Ohshima Toshio
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13617
Subject(s) - pars compacta , mptp , neurodegeneration , substantia nigra , dopaminergic , microglia , neuroscience , neuroinflammation , parkinson's disease , biology , chemistry , inflammation , dopamine , medicine , immunology , disease
Parkinson's disease ( PD ) is a progressive neurodegenerative disorder that is characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta ( SN c). Several lines of evidence suggest that neurodegeneration in PD is accelerated by a vicious cycle in which apoptosis in dopaminergic neurons triggers the activation of microglia and harmful inflammatory processes that further amplify neuronal death. Recently, we demonstrated that the deletion of collapsin response mediator protein 4 ( CRMP 4) suppresses inflammatory responses and cell death in a mouse model of spinal cord injury, leading to improved functional recovery. We thus hypothesized that Crmp4 −/− mice may have limited inflammatory responses and a decrease in the loss of SN c dopaminergic neurons in an 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine ( MPTP )‐induced PD mouse model. We observed CRMP 4 expression in neurons, astrocytes, and microglia/macrophages following the injection of 25 mg/kg MPTP . We compared the number of dopaminergic neurons and the inflammatory response in SN c between Crmp4 +/+ and Crmp4 −/− mice after MPTP injection. Limited loss of SN c dopaminergic neurons and decreased activations of microglia and astrocytes were observed in Crmp4 −/− mice. These results suggest that CRMP 4 is a novel therapeutic target in the treatment of PD patients.We demonstrated that genetic CRMP4 deletion delays a vicious cycle of inflammation and neurodegeneration in a Parkinson's disease mouse model. MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) injection to wild‐type mice induces collapsin response mediator protein 4 (CRMP4) up‐regulation in neurons, astrocytes, and microglia. CRMP4‐deficient mice show reduced inflammation and suppressed dopaminergic neuronal death after MPTP injection. These findings suggest that CRMP4 deletion may be a new therapeutic strategy against Parkinson's diseases.