Open AccessP2Y 12 deficiency in mouse impairs noradrenergic system in brain, and alters anxiety‐like neurobehavior and memory
Author(s) -
Zheng F.,
Zhou Q.,
Cao Y.,
Shi H.,
Wu H.,
Zhang B.,
Huang F.,
Wu X.
Publication year - 2019
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12458
Subject(s) - creb , morris water navigation task , neuroscience , purinergic receptor , signal transduction , hippocampus , endocrinology , neurotrophic factors , medicine , elevated plus maze , cyclic amp response element binding protein , receptor , psychology , biology , anxiety , microbiology and biotechnology , psychiatry , transcription factor , biochemistry , gene
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 α receptors, subtypes α2 (ARα2b) 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.