Studies on aging processes

By means of computer assisted morphometry and microdensitometry it has been possible to characterize aging processes in transmitter identified neurons demonstrated at the presynaptic level by immunocytochemistry and at the postsynaptic level by receptor autoradiography. Three-month- and 24-month-old rats were used in the present study. It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact. In this quantitative receptor autoradiographical analysis 3H-spiperone and 3H-N-propyl-norapomorphine were used as radioligands for DA receptors. In comparison with the aging induced changes in DA receptors in the striatum and in the nucleus accumbens the alpha 2- and the beta-adrenergic receptors appeared to be more resistant to the aging process. In the analysis of the opiate receptors of the aging brain it could be demonstrated by quantitative receptor autoradiography using both radioligands for the mu-type (3H-etorphin) and delta-type (3H-d-ala2-d-leu5-enkephalin) of opiate receptors that there is a marked and widespread disappearance of both types of opiate receptors in the aging brain. It must be emphasized that no correlation exists in the degeneration pattern of the mu- and delta-type of opioid receptors indicating that they may represent two separate entities with separate trophic regulation. In contrast, it was discovered in the quantitative receptor autoradiographical analysis that 3H-flunitrazepam binding was increased in many areas of the aging brain compared with the adult rat brain. These results underline the heterogeneity in the degenerative patterns which take place in transmitter receptors in relation to aging. Thus, these results indicate that the simple replacement therapy in aged patients may not give optimal results. As a matter of fact, such treatments can lead to a further unbalance between the various types of transmitter identified neurons building up the neuronal networks of the brain, which are undergoing degeneration.