Carvedilol reestablishes long-term potentiation in a mouse model of Alzheimer's disease.
In this study, we examined acute effects of carvedilol, a nonselective alpha/beta-adrenergic receptor blocker, on neuronal transmission and long-term potentiation (LTP) in six month-old TgCRND8 mice and their wild-type age-matched controls. Field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus from carvedilol- or vehicle dimethyl sulfoxide-treated slices, and differences in basal synaptic transmission and LTP were assessed. Carvedilol treatment produced a significant increase in basal synaptic transmission and LTP in TgCRND8 mice, as compared to their vehicle-treated slices, in which basal neuronal transmission and LTP decreased. Interestingly, carvedilol significantly suppressed spontaneous seizure activity in TgCRND8 mice as measured by the number of slices showing epileptic discharges as well as the number of spikes within these and the amplitude of the second spike, measured at baseline and end of recording. In contrast, vehicle-treated slices in TgCRND8 mice did not show a significant decrease in epileptic discharges. These results suggest that carvedilol reestablishes basal synaptic transmission, enhances neuronal plasticity and suppresses neuronal hyperexcitability in TgCRND8 mice.
Arrieta-Cruz
Isabel
I
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Wang
Jun
J
Pavlides
Constantine
C
Pasinetti
Giulio Maria
GM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D011412:Propanolamines / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol