Co-grafts of muscle cells and mesencephalic tissue into hemiparkinsonian rats: Behavioral and histochemical effects

Extracts from skeletal muscle cell cultures have been shown to increase lev els of the enzyme tyrosine hydroxylase (TH) and promote survival of differe nt types of developing neurons in vitro. To determine the effect of muscle cell cografts on the survival of dopamine neurons in a rat model of Parkins on's disease, we transplanted an embryonic day (ED)-15 rat mesencephalic ce ll suspension alone or with neonatal muscle cells into B-hydroxydopamine (6 -OHDA) denervated rat striatum, In parallel experiments conducted in vitro, we cultured ED-15 rat mesencephalon or rat striatum in conditioned medium from neonatal rat muscle cultures (MC-CM), Our results showed that: (A) in vitro, MC-CM increased the number of TH-immunoreactive (TH-IR) neurons in e mbryonic mesencephalic cultures but did not induce expression of TH in embr yonic striatal cultures; (B) in vivo, animals with co-grafts of muscle cell s and ED-15 mesencephalon had more TH-IR in the grafted striatum compared t o animals that received mesencephalic cells grafts alone, although the graf t-induced reversal of circling behavior in response to methamphetamine was the same in both transplanted groups; and (C) grafts of muscle cells alone did not induce TH-IR in the denervated striatum and did not reduce methamph etamine-induced circling. These findings suggest that in vivo, neonatal mus cle cells secrete factors that promote survival and/or outgrowth of fetal m idbrain dopamine cells and improve the levels of TH-IR in grafted striatum, (C) 2000 Elsevier Science Inc.