Table 1. Mouse model features that recapitulate PD. General definitions of the models: appear below*.
| Toxin | Time to greatest DA cell loss |
Striatal DA loss | DAergic cell loss in SN |
Inclusions |
|---|---|---|---|---|
| Single dose MPTP (30 mg/kg in mice) |
12 hours | >80% loss of DA after 1 day and >40% loss after 30 days |
20-30% | Not examined |
| MPTP, acute* (mice) |
12 hours | >90% loss of DA 7 days after treatment |
40% | None |
| MPTP, subchronic (subacute)* in mice |
12 hours | 53% loss of DA 30 days after treatment |
24-40% | None |
| MPTP/P, chronic* in mice |
3 weeks post- treatment |
95-98% loss of DA 3 weeks after treatment; 76% loss after 6 months |
50% post- treatment and 70% 3 weeks post-treatment |
Proteinaceous and lipid inclusions in secondary lysosomes that are α-synuclein- positive but do not resemble Lewy bodies |
| MPTP, chronic* with escalating doses in mice |
At the end of treatment (4 weeks) |
Dose-dependent loss of DA; greater than 70% loss of DA with the two highest doses only |
24% loss after 1 week and 62% after 4 weeks following the highest dose |
Not examined |
| MPTP, chronic* with mini-pumps in mice |
21 days | 85% loss of DA metabolites in dorsal striatum |
75-80% | α-synuclein- positive inclusions that do not resemble Lewy bodies inclusions |
| MPP+, chronic pump in rats |
42 days or longer |
Dose-dependent loss of DA |
40% | No inclusions in DA neurons |
*
MPTP, acute – 4 injections of MPTP in one 24 h period, 2 hours apart; injections are generally 20-30 mg/kg
*
MPTP, subchronic (subacute) – daily injections over 5 – 10 days. The toxin injected varies from 15mg/kg to 30mg/kg
*
MPTP, chronic –
- MPTP/P model, 25 mg/kg injected every 3.5 days for 5 weeks;
- Minipump delivery is continuous, either s.c. or i.p.; 23 or 46 mg/kg/day for 14 days or 46 mg/kg/day for 28 days;
- Escalating dose model included daily injections for 5 days, with the weekend off for 4 weeks. The injected doses were scaled up over time from 4 mg/kg to 32 mg/kg