PMID- 28890075
OWN - NLM
STAT- MEDLINE
DCOM- 20171106
LR  - 20191210
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 298
IP  - Pt A
DP  - 2017 Dec
TI  - Down-regulation of dorsal striatal alphaCaMKII causes striatum-related cognitive and 
      synaptic disorders.
PG  - 112-121
LID - S0014-4886(17)30234-0 [pii]
LID - 10.1016/j.expneurol.2017.09.004 [doi]
AB  - Alpha calcium/calmodulin dependent protein kinase II (alphaCaMKII) is a 
      serine/threonine protein kinase which is expressed abundantly in dorsal striatum 
      and is highly involved in the corticostriatal synaptic plasticity. Nevertheless, 
      it currently remains unclear whether and how alphaCaMKII plays a in the 
      striatum-related neural disorders. To address the above issue, 
      lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression 
      of alphaCaMKII gene in the dorsal striatum of mice. As a consequence of 
      down-regulation of dorsal striatal alphaCaMKII expression, we observed defective 
      motor skill learning in accelerating rotarod and response learning in water cross 
      maze. Furthermore, impaired corticostriatal basal transmission and long-term 
      potentiation (LTP), which correlated with the deficits in dorsal striatum-related 
      cognition, were also detected in the alphaCaMKII-shRNA mice. Consistent with the 
      above results, alphaCaMKII-shRNA mice exhibited a remarkable decline in GluA1-Ser831 
      and GluA1-Ser845 phosphorylation levels of 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and a 
      decline in the expression levels of N-methyl-d-aspartic acid receptor (NMDAR) 
      subunits NR1, NR2A and NR2B. Taken together, alphaCaMKII down-regulation caused 
      dorsal striatum-related cognitive disorders by inhibiting corticostriatal 
      synaptic plasticity, which resulted from dysfunction of AMPARs and NMDARs. Our 
      findings demonstrate for the first time an important role of alphaCaMKII in 
      striatum-related neural disorders and provide further evidence for the 
      proposition that corticostriatal LTP underlies aspects of dorsal striatum-related 
      cognition.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Wang, Qi
AU  - Wang Q
AD  - Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal 
      University, Shanghai 200062, China.
FAU - Yin, Pengcheng
AU  - Yin P
AD  - Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal 
      University, Shanghai 200062, China.
FAU - Yu, Bin
AU  - Yu B
AD  - Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal 
      University, Shanghai 200062, China.
FAU - Zhao, Zheng
AU  - Zhao Z
AD  - Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal 
      University, Shanghai 200062, China.
FAU - Richter-Levin, Gal
AU  - Richter-Levin G
AD  - "Sagol" Department of Neurobiology, University of Haifa, Haifa 31905, Israel.
FAU - Yu, Lu
AU  - Yu L
AD  - Department of Chinese Internal Medicine, Putuo Hospital, Shanghai University of 
      Traditional Chinese Medicine, Shanghai 200062, China.
FAU - Cao, Xiaohua
AU  - Cao X
AD  - Key Laboratory of Brain Functional Genomics, MOE & STCSM, East China Normal 
      University, Shanghai 200062, China. Electronic address: xhcao@brain.ecnu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170908
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (CaMKII inhibitor AIP)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Camk2n1 protein, rat)
RN  - 0 (Carrier Proteins)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins
MH  - Carrier Proteins/antagonists & inhibitors/*metabolism
MH  - Cognition Disorders/*metabolism
MH  - Corpus Striatum/drug effects/*metabolism
MH  - Down-Regulation/drug effects/*physiology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuronal Plasticity/drug effects/physiology
MH  - Organ Culture Techniques
MH  - Peptides/pharmacology
MH  - Synapses/drug effects/*metabolism
OTO - NOTNLM
OT  - AMPAR
OT  - Long term potentiation
OT  - NMDAR
OT  - Neural disorders
OT  - Striatum
OT  - alphaCaMKII
EDAT- 2017/09/12 06:00
MHDA- 2017/11/07 06:00
CRDT- 2017/09/12 06:00
PHST- 2017/03/15 00:00 [received]
PHST- 2017/08/25 00:00 [revised]
PHST- 2017/09/06 00:00 [accepted]
PHST- 2017/09/12 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2017/09/12 06:00 [entrez]
AID - S0014-4886(17)30234-0 [pii]
AID - 10.1016/j.expneurol.2017.09.004 [doi]
PST - ppublish
SO  - Exp Neurol. 2017 Dec;298(Pt A):112-121. doi: 10.1016/j.expneurol.2017.09.004. 
      Epub 2017 Sep 8.