TY - JOUR
T1 - Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCβII correlates with intensified fear-induced conflict behavior
AU - Birikh, Klara R.
AU - Sklan, Ella H.
AU - Shoham, Shai
AU - Soreq, Hermona
PY - 2003/1/7
Y1 - 2003/1/7
N2 - Behavioral reactions to stress are altered in numerous psychiatric and neurodegenerative syndromes, but the corresponding molecular processes and signal transduction pathways are yet unknown. Here, we report that, in mice, the stress-induced splice variant of acetylcholinesterase, AChE-R, interacts intraneuronally with the scaffold protein RACK1 and through it, with its target, protein kinase CβII (PKCβII), which is known to be involved in fear conditioning. In stress-responsive brain regions of normal FVB/N mice, the mild stress of i.p. injection increased AChE and PKCβII levels in a manner suppressible by antisense prevention of AChE-R accumulation. Injection stress also prolonged conflict between escape and hiding in the emergence into an open field test. Moreover, transgenic FVB/N mice overexpressing AChE-R displayed prolonged delay to emerge into another field (fear-induced behavioral inhibition), associated with chronically intensified neuronal colabeling of RACK1 and PKCβII in stress-responsive brain regions. These findings are consistent with the hypothesis that stress-associated changes in cholinergic gene expression regulate neuronal PKCβII functioning, promoting.
AB - Behavioral reactions to stress are altered in numerous psychiatric and neurodegenerative syndromes, but the corresponding molecular processes and signal transduction pathways are yet unknown. Here, we report that, in mice, the stress-induced splice variant of acetylcholinesterase, AChE-R, interacts intraneuronally with the scaffold protein RACK1 and through it, with its target, protein kinase CβII (PKCβII), which is known to be involved in fear conditioning. In stress-responsive brain regions of normal FVB/N mice, the mild stress of i.p. injection increased AChE and PKCβII levels in a manner suppressible by antisense prevention of AChE-R accumulation. Injection stress also prolonged conflict between escape and hiding in the emergence into an open field test. Moreover, transgenic FVB/N mice overexpressing AChE-R displayed prolonged delay to emerge into another field (fear-induced behavioral inhibition), associated with chronically intensified neuronal colabeling of RACK1 and PKCβII in stress-responsive brain regions. These findings are consistent with the hypothesis that stress-associated changes in cholinergic gene expression regulate neuronal PKCβII functioning, promoting.
UR - http://www.scopus.com/inward/record.url?scp=0037422539&partnerID=8YFLogxK
U2 - 10.1073/pnas.0135647100
DO - 10.1073/pnas.0135647100
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C2 - 12509514
AN - SCOPUS:0037422539
SN - 0027-8424
VL - 100
SP - 283
EP - 288
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -