The Journal of Neuroscience, July 1, 2001, 21(13):4901-4907
Expression of Striatal Preprotachykinin mRNA in Symptomatic and
Asymptomatic 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Exposed
Monkeys Is Related to Parkinsonian Motor Signs
Timothy V.
Wade and
Jay S.
Schneider
Department of Pathology, Anatomy, and Cell Biology, Thomas
Jefferson University, Philadelphia, Pennsylvania 19107
Striatal preprotachykinin (PPT) gene expression and
[3H]mazindol binding were examined in monkeys
exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Some
animals (n = 5) became moderately to severely
parkinsonian after receiving large doses of MPTP over 9-30 d and
remained symptomatic for a relatively short time (3 weeks to 3 months;
acutely symptomatic group). A second group of animals
(n = 5) received low doses of MPTP (1.5-12
months), developed cognitive impairments but displayed no gross motor
deficits (asymptomatic group), and were killed 3-12 months after their
final dose of MPTP. Other animals became moderately to severely
parkinsonian after receiving escalating doses of MPTP (>6 months;
n = 4) or high doses of MPTP (<1 month; n = 1) and remained symptomatic for 2.5-5.75 years
(chronically symptomatic group). All MPTP-treated animals had
extensive losses of [3H]mazindol binding in dorsal
striatal sensorimotor regions with asymptomatic animals generally
having a lesser degree of damage. However, PPT mRNA levels differed
sharply among treatment groups. Symptomatic animals (acutely and
chronically parkinsonian) had significantly decreased PPT mRNA levels
in most striatal regions. In asymptomatic animals, PPT mRNA expression
was not significantly different from that measured in control animals,
despite decreases in [3H]mazindol binding in some
striatal regions of similar magnitude to those observed in symptomatic
animals. These observations suggest that PPT gene expression may be
directly related to expression of parkinsonian motor symptomatology
regardless of duration of MPTP exposure, duration of the parkinsonism,
or extent of dopamine denervation. These results imply that the direct
striatal output circuit may have a greater contribution to expression
of parkinsonian symptomatology than proposed previously.
Key words:
preprotachykinin; striatum; parkinsonism; dopamine; MPTP; monkey
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134901-07$05.00/0