TY - JOUR
T1 - Valproic Acid-Induced Anxiety and Depression Behaviors are Ameliorated in p39 Cdk5 Activator-Deficient Mice
AU - Takahashi, Miyuki
AU - Takasugi, Toshiyuki
AU - Kawakami, Arisa
AU - Wei, Ran
AU - Ando, Kanae
AU - Ohshima, Toshio
AU - Hisanaga, Shin ichi
N1 - Funding Information:
We would like to thank Dr. H. Kobayashi at Tokyo Metropolitan University for supporting the research.
Funding Information:
This work was supported in part by a grant-in-aid MEXT (16K07060 and 19K06942 to S.H.), by a grant from JSPS (16J05051 to MT), and by The Uehara Memorial Foundation.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/9
Y1 - 2022/9
N2 - Valproic acid (VPA) is a drug used for the treatment of epilepsy, seizures, migraines, and bipolar disorders. Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase activated by p35 or p39 in neurons and plays a role in a variety of neuronal functions, including psychiatric behaviors. We previously reported that VPA suppressed Cdk5 activity by reducing the expression of p35 in cultured cortical neurons, leaving p39 unchanged. In this study, we asked for the role of Cdk5 in VPA-induced anxiety and depression behaviors. Wild-type (WT) mice displayed increased anxiety and depression after chronic administration of VPA for 14 days, when the expression of p35 was decreased. To clarify their relationship, we used p39 knockout (KO) mice, in which p35 is the only Cdk5 activator. When p39 KO mice were treated chronically with VPA, unexpectedly, they exhibited fewer anxiety and depression behaviors than WT mice. The effects were p39 cdk5r2 gene-dosage dependent. Together, these results indicate that Cdk5-p39 plays a specific role in VPA-induced anxiety and depression behaviors.
AB - Valproic acid (VPA) is a drug used for the treatment of epilepsy, seizures, migraines, and bipolar disorders. Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase activated by p35 or p39 in neurons and plays a role in a variety of neuronal functions, including psychiatric behaviors. We previously reported that VPA suppressed Cdk5 activity by reducing the expression of p35 in cultured cortical neurons, leaving p39 unchanged. In this study, we asked for the role of Cdk5 in VPA-induced anxiety and depression behaviors. Wild-type (WT) mice displayed increased anxiety and depression after chronic administration of VPA for 14 days, when the expression of p35 was decreased. To clarify their relationship, we used p39 knockout (KO) mice, in which p35 is the only Cdk5 activator. When p39 KO mice were treated chronically with VPA, unexpectedly, they exhibited fewer anxiety and depression behaviors than WT mice. The effects were p39 cdk5r2 gene-dosage dependent. Together, these results indicate that Cdk5-p39 plays a specific role in VPA-induced anxiety and depression behaviors.
KW - Anxiety
KW - Cdk5
KW - Depression
KW - Psychiatric behavior
KW - Valproic acid
KW - p39
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U2 - 10.1007/s11064-022-03642-9
DO - 10.1007/s11064-022-03642-9
M3 - Article
C2 - 35674931
AN - SCOPUS:85131577624
SN - 0364-3190
VL - 47
SP - 2773
EP - 2779
JO - Neurochemical Research
JF - Neurochemical Research
IS - 9
ER -