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. These excitatory neurons project into the hippocampus. At this stage ('entorhinal' case), while neurofibrillary tangles are still absent from the hippocampus, a significant reduction in hippocampal adenylate cyclase activity has been detected. To test whether this reduction is a consequence of a deafferentation (and thus not a specifically disease-related alteration), we performed unilateral electrolytic lesions and sham-operations of the rat entorhinal cortex. The animals were killed 2, 12 and 55 days post lesion (dpl) and hippocampal adenylate cyclase activity was assayed. The major results were as follows: (1) both lesioned and unlesioned sides showed higher activity than a sham-operated control; (2) the adenylate cyclase activity of the lesioned side increased to a significantly lesser degree than that of the unlesioned side at 12 dpl; (3) this 'decrease' was attributed to changes in G protein-mediated activation of adenylate cyclase; (4) at no time point post lesion did the pattern of rat adenylate cyclase activity resemble that observed in Alzheimer's disease. Our data suggests that the loss of entorhinal afferents alone cannot explain the reduction in cyclase-activity seen in 'entorhinal' cases.
Ohm
T G
TG
Institut für Anatomie, Universitätsklinikum Charité, D-10098 Berlin, Germany. thomas_georg.ohm@charite.de
von Dewitz
G
G
Witte
K
K
Nitsch
R
R
Lemmer
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D003714:Denervation; D018728:Entorhinal Cortex / Q000293:injuries / Q000502:physiology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013997:Time Factors
D006165:Guanylyl Imidodiphosphate; D008345:Manganese; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008274:Magnesium