Changes in Ca(2+)/calmodulin-dependent protein kinase II activity and its relation to performance in passive avoidance response and long-term potentiation formation in mice prenatally exposed to diethylstilbestrol.
We investigated the effects of prenatal exposure to diethylstilbestrol (DES), an endocrine disrupter on learning behavior and synaptic functions. Specifically, we determined the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and related kinases that play an essential role in long-term potentiation (LTP) in the hippocampus in mice that were prenatally exposed to DES. Treatment with DES resulted in increased CaMKII autophosphorylation and Ca(2+)-independent activity in the hippocampus and cortex of male mice. Impaired passive avoidance correlated with this increased CaMKII autophosphorylation, as did the enhanced early phase of LTP (E-LTP) in hippocampus. These data suggest that prenatal exposure to DES induces deficits in passive avoidance responses as a result of increased CaMKII activity and hippocampal LTP.
Kaitsuka
T
T
Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Fukunaga
K
K
Soeda
F
F
Shirasaki
T
T
Miyamoto
E
E
Takahama
K
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D007859:Learning Disabilities / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology
D004054:Diethylstilbestrol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases