PMID- 29341465
OWN - NLM
STAT- MEDLINE
DCOM- 20190321
LR  - 20190321
IS  - 1601-183X (Electronic)
IS  - 1601-183X (Linking)
VI  - 18
IP  - 2
DP  - 2019 Feb
TI  - P2Y(12) deficiency in mouse impairs noradrenergic system in brain, and alters 
      anxiety-like neurobehavior and memory.
PG  - e12458
LID - 10.1111/gbb.12458 [doi]
AB  - Purinergic receptor P2Y(12) (P2Y(12) ), a G protein-coupled purinergic receptor, 
      is widely distributed in nervous system and involved in the progression of 
      neurological diseases such as multiple sclerosis and neuropathic pain. The 
      central noradrenergic system actively participates in a number of 
      neurophysiological processes. Nevertheless, whether there is any direct relevance 
      between P2Y(12) and noradrenergic signal transduction remains unknown. In the 
      present study, we tested the hypothesis that lack of P2Y(12) impaired 
      noradrenergic signal transduction in mouse brain. Our results showed that P2Y(12) 
      knockout (KO) mice exhibited increased anxiety-like behavior in the open-field 
      test (OFT) and elevated plus maze test and displayed deficits in memory in the 
      radial-arm maze test (RAMT) and Morris water maze test (MWMT). They also 
      exhibited reduced locomotion in the OFT and MWMT. Moreover, loss of P2Y(12) 
      decreased the level of noradrenaline and the expression of noradrenergic alpha 
      receptors, subtypes alpha2 (ARalpha2b) in mouse cerebellum and hippocampus. Meanwhile, it 
      hampered the protein kinase A (PKA)/cAMP response element-binding protein 
      (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in these brain 
      regions. Taken together, our results showed for the first time that P2Y(12) KO 
      altered the anxiety, memory and locomotion of mice, which was closely associated 
      with abnormal state of noradrenergic system in the brain. The findings implicate 
      that P2Y(12) plays an indispensable role in noradrenergic signal transduction; 
      its deficit is insufficient to limit anxiety responses or supports cognitive 
      performance and activity.
CI  - (c) 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics 
      Society.
FAU - Zheng, F
AU  - Zheng F
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Zhou, Q
AU  - Zhou Q
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Cao, Y
AU  - Cao Y
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Shi, H
AU  - Shi H
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Wu, H
AU  - Wu H
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Zhang, B
AU  - Zhang B
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Huang, F
AU  - Huang F
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Wu, X
AU  - Wu X
AUID- ORCID: 0000-0001-6554-5341
AD  - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education 
      (MOE) Key Laboratory for Standardization of Chinese Medicines, The State 
      Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 
      Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180209
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Receptors, Adrenergic, alpha)
RN  - 0 (Receptors, Purinergic P2Y12)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Anxiety/*genetics
MH  - Brain/*metabolism/physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Female
MH  - *Memory
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Norepinephrine/metabolism
MH  - Receptors, Adrenergic, alpha/genetics/*metabolism
MH  - Receptors, Purinergic P2Y12/deficiency/genetics/*metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - P2Y12
OT  - anxiety
OT  - locomotion
OT  - memory
OT  - noradrenaline
EDAT- 2018/01/18 06:00
MHDA- 2019/03/22 06:00
CRDT- 2018/01/18 06:00
PHST- 2017/10/19 00:00 [received]
PHST- 2017/12/08 00:00 [revised]
PHST- 2018/01/11 00:00 [accepted]
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2019/03/22 06:00 [medline]
PHST- 2018/01/18 06:00 [entrez]
AID - 10.1111/gbb.12458 [doi]
PST - ppublish
SO  - Genes Brain Behav. 2019 Feb;18(2):e12458. doi: 10.1111/gbb.12458. Epub 2018 Feb 
      9.