Basal and stimulated hippocampal adenylate cyclase activity in the experimentally lesioned rat entorhinal cortex

Early stage development of Alzheimer-related neurofibrillary tangles occurs primarily in neurons of entorhinal cortex layers pre-alpha and pre-beta. T hese excitatory neurons project into the hippocampus. At this stage ('entor hinal' case), while neurofibrillary tangles are still absent from the hippo campus a significant reduction in hippocampal adenylate cyclase activity ha s been detected. To test whether this reduction is a consequence of a deaff erentation (and thus not a specifically disease-related alteration), we per formed unilateral electrolytic lesions and sham-operations of the rat entor hinal cortex. The animals were killed 2, 12 and 55 days post lesion (dpl) a nd hippocampal adenylate cyclase activity was assayed. The major results we re as follows: (1) both lesioned and unlesioned sides showed higher activit y than a sham-operated control; (2) the adenylate cyclase activity of the l esioned side increased to a significantly lesser degree than that of the un lesioned side at 12 dpl; (3) this 'decrease' was attributed to changes in G protein-mediated activation of adenylate cyclase; (4) at no time point pos t lesion did the pattern of rat adenylate cyclase activity resemble that ob served in Alzheimer's disease. Our data suggests that the loss of entorhina l afferents alone cannot explain the reduction in cyclase-activity seen in 'entorhinal' cases.