Table 3. Microglia activation and neuroinflammation in rodent models of nigral dopaminergic cell death.

MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-OHDA, 6-hydroxi-dopamine; AAV, adeno associated virus; MHC I/II, major histocompatibility complex I/II; MFB: medial forbrain bundle; TLR, Toll-like-receptor; TH, thyrosine hydroxylase; DA, dopaminergic; SN, substantia nigra; Str, striatum; α-Syn, α-synuclein; WT, wild-type; Tg, transgenic; mo, months; wks, weeks; d, day(s); hr, hour(s); nd, not determined.

Model	Species	TH+cell loss in SN	TH+fibre loss in Str	Gliosis in SN	MHC II	CD68	Comment	Reference
Subchronic MPTP	Mouse	2 hr peak d7	2 hr recovered by d28	Peak at d1, persists at lower levels to d21	2 hr	nd	C1q expression (after 2 hr)	Depboylu et al., 2011
Intravenous MPTP, chronic vs subacute	Cynomolgus monkey	Subacute <acute	nd	nd	all positive; peak at 6 mo for chronic and persists to 35 mo	nd	Vazquez-Claverie et al., 2009)
Unilateral intra-SN delivery of two different dose of AAV2/4-αSyn	Rat	Only at high α-syn dose (4 wks)	Progressive in both groups high >> low dose	Neurodegeneration of greater magnitude; peak at 4 wks and prior to cell death (8 wks)	Neurodegeneration > cell death; peak at 4 wks, persists to 15 wks	Only cell death, at all times, peak 8 wks	T cells and B cell infiltration, neurodegeneration; MHC II+ in Str	Sanchez-Guajardo et al., 2010
Unilateral intra-SN delivery of AAV2/5-WT or A53T α Syn	Marmoset monkey	A53T α-syn after 12 mo	nd	WT 100% increase A53T 80% increase	A53T > WT	nd	HLA-DR+ CD19+ cells; 4 morphologies, A53T more polarized than WT	Barkholt et al., 2012
Unilateral intra-SN delivery of AAV2-α-Syn	Mouse	nd	nd	nd	nd	4 wks, 2 and 12 mo	stereologic quantification of lymphocytes; IgG deposition	Theodore et al., 2008
Unilateral injection 6-OHDA in MFB	Rat	From d3 peak d9	nd	From d1; peak d15	From d1; peak at d9 (>CD68); persists to d15	From d3 peak at d15 (>MHC II)	MHC II in contact with neurites or live cells; CD68 in contact with caspase+ cells	Marinova-Mutafchieva et al., 2009
Unilateral injection 6-OHDA in nigrostriatal system	Rat	50% d1	nd	From d5 activated; peak at d7–14 and persists to d35	nd	nd	Two morphologically distinct microglia; activated: big stoma, short processes	Henry et al., 2009
Unilateral injection 6-OHDA in nigrostriatal system	rat	nd	nd	nd	from d4-6, d6< MHC I d30 present (no MHC I); d90 absent	nd	MHC I: d3 look like leucocytes, d4–6 microglia	Akiyama and McGeer, 1989
Intranasal injection of 6-OHDA	Rat	50%	75%	Yes	nd	nd	Preceded onset of dopaminergic loss	Armentero et al., 2006
Transgenic α-Syn overexpression	Tg mice (Thy1 promoter)	Non	Non	From 1mo in Str; from 5-6mo in SN	After 14mo in Str	nd	Gliosis and MHC II expression independent of DA cell loss; T cells ↑in serum (22 mo); Altered TLR expression	Watson et al., 2012