Modulation of mouse brain cortex adrenoceptor in old mice by supplementation of zinc and thymomodulin.
BACKGROUND
Previous experiments have shown that the age-related decrease of mouse brain cortex adrenoceptor density can be recovered by grafting a neonatal thymus into old recipients. The question arises whether similar results can also be obtained in the presence of a single thymic factor such as thymomodulin (TMD). It is worth noting that the activity of some thymic factors is strictly zinc (Zn) dependent and that their age-related decreased production is recovered in old mice supplemented with Zn.


OBJECTIVE
The above-mentioned evidences prompted us to verify whether Zn and TMD, either alone or combined, are able to induce some corrective effects on age-dependent alterations of adrenoceptor characteristics of the mouse brain cortex.


METHODS
Thus, we performed experiments on four groups of Balb/c mice treated with saline, Zn, TMD, or both Zn and TMD. Treatments started when animals were 18 months old and ran for 6 months. The alpha(1)- and beta-Adrenoceptor characteristics were assayed by steady state binding analysis using labelled prazosine and iodocyanopindolol, respectively. Data were analyzed using one-way analysis of variance, followed, when appropriate, by multiple-comparison analysis.


RESULTS
Results show an increase of beta-adrenoceptor density and a decrease of alpha(1)-adrenoceptor density in both Zn- and Zn+TMD-treated animals when compared to saline-treated controls, while receptor affinities did not change significantly.


CONCLUSIONS
The lack of action of TMD suggests that this type of treatment cannot mimic the effects of grafting the whole gland; it cannot be excluded that different time-dose schedule could be more effective. Zn treatment, on the other hand, does modulate adrenoceptors; however, it shows a corrective action on the age-related decreased density of beta-adrenoceptors, but further decreases that of alpha(1)-adrenoceptors. This differential action could be due to their differential physiological role.
Viticchi
C
C
Biotechnology, Gerontological Research Department INRCA, Ancona, Italy. c.viticchi@inrca.it
Moresi
R
R
Piantanelli
L
L
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011869:Radioligand Assay; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013949:Thymus Extracts / Q000494:pharmacology*; D015854:Up-Regulation; D015032:Zinc / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013949:Thymus Extracts; C051006:thymomodulin; D015032:Zinc