Rapid neurotrophic actions of an ACTH/MSH(4-9) analogue after nigrostriatal XXXX lesioning.

@entity669 @entity935 @entity3826 @entity35 @entity4944 @entity2955 @entity14480 @entity2359
ACTH peptide fragments demonstrate potent neurotrophic effects on peripheral nerves in situ, central neurons in culture, and have been implicated to have effects on central neurons in vivo. @entity2359 lesioning of the nigrostriatal system, which depletes the striatum of @entity935 , provides a feasible model of central regeneration in which to test these peptides. Male @entity35 were lesioned unilaterally with @entity2955 (8 micrograms/4 microliters), infused into the substantia nigra. They were subsequently treated with 10 micrograms/kg IP of @entity14480 [ACTH/MSH(4-9) analogue] or saline every 24 h starting immediately after the infusion and were observed for 2 weeks. Rotational behavior data indicate that @entity14480 significantly decreases ipsiversive turning (p < 0.05), induced by @entity4944 (2 mg/kg), as well as accelerating the onset of denervation supersensitivity induced by @entity3826 (0.05 mg/kg). Evaluation of @entity935 immunohistochemistry, using an anti- @entity669 hydroxylase antibody, demonstrates an enhanced intensity of staining in the @entity14480 -treated tissue compared to its saline counterpart. This difference is confirmed and quantified through specific high-affinity @entity935 uptake. @entity935 uptake is about 17% higher in the striata of animals treated with @entity14480 . Higher @entity935 uptake levels in these ACTH-treated animals correlate with greater fiber density in this group. Therefore, it appears that treatment with the ACTH/MSH(4-9) analogue @entity14480 (10 micrograms/kg/24 h) offers a protective effect from @entity2955 lesions in the substantia nigra as well as accelerating various compensatory mechanisms involved in functional recovery.
