Impairment of CREB phosphorylation in the hippocampal CA1 region of the senescence-accelerated mouse (SAM) P8.

Senescence-accelerated mouse P8 (SAMP8) mice show deficits of learning and memory at an early age. However, no evidence of neurochemical changes was found in the hippocampus of SAMP8 at an early age. After electric shock in the passive avoidance test, SAMR1 (normal aging mice) showed biphasic responses in the phosphorylated CREB (p-CREB) level in the hippocampal CA1 region: an early peak detected at 1 to 3 h was followed by a marked drop at 6 h, and a second peak rise starting after 9 to 12 h after electric stimulation. On the other hand, SAMP8 manifested one peak in the p-CREB level 9 h after the stimulation. Since the phosphorylation of CREB plays an important role for synaptic plasticity and consolidation of long-term memory, the impairment of CREB phosphorylation in the hippocampal CA1 region of SAMP8 may cause learning and memory deficits.