Table 1.
Degeneration of nigrostriatal dopaminergic pathway, α-synuclein pathology, motor deficits, extranigral pathology and non-motor deficits in stereotaxic, systemic and intranasal LPS models.
| Route of administration | Species | Dose of LPS | Duration of experiment Day (d), week (w) month (m) |
TH positive neurons in SN or TH protein |
Striatal dopamine | Αlpha-synuclein protein/aggregates in SN | Motor deficits | Extranigral pathology | Non-motor deficits |
|---|---|---|---|---|---|---|---|---|---|
| Stereotaxic (single dose) | Rats | 0.6–16 μg (intranigral) | 1w6,7, 3w4,8, 4w1,2,5, and 6w3 | TH neurons 50–80% ↓1,2,3,4,5 | 34–50% ↓3,4 | Not assessed | ↑ rotational behaviour1,2,3,4,6,7 and ↓ time on the rotarod3,5 | Not assessed | Impaired memory6, Anxiety and depressive-like behaviour7, and Gastric dysmotility8 |
| Rats | 30–32 μg (intra-striatal) | 1w9,10,11, 2w and 4w9 | TH neurons 21% ↓ in 1w9,10,11, 38 and 41% ↓ in 2w and 4w9 |
40–42% ↓9,10 | ↑ α-syn protein9 | ↑ rotational behaviour9 | Not assessed | Not assessed | |
| C57BL/6 Mice | 20 μg (intrastriatal) |
1w, 4w and 12w12 | TH neurons 26% ↓ in 1w, 72% ↓ in 4w and 81% ↓ in 12w12 | 42% ↓ in 4w12 | Not assessed | ↓ time on the rotarod12 | Not assessed | Not assessed | |
| B6.129S6-Cybbtm 1Din mice, non-transgenic mice (nTg) (C57BL and 129/Sv) and transgenic mice expressing human WT (M7KO) and A53T mutant α-syn (M83KO) | 5 μg (intranigral) | 2w34, 4w35 | TH neurons 44% ↓34, TH neurons 35% ↓ nTg, 48% ↓ M7KO and M83KO 65% ↓35 | Not assessed | α-syn aggregates in TH neurons35 | Not assessed | Not assessed | Not assessed | |
|
(No studies for repeated LPS injections in rats) Systemic (i.p) |
C57BL/6 mice | 250 μg/kg daily for 7 days | 7d15, 13d13, 14d14 | TH protein 87% ↓13 | Not assessed | 3.8-fold ↑ α-syn protein13 | Not assessed | 4.2-fold ↑ in α-syn protein13 and 8-fold ↓ in TH protein in hippocampus13. | Impaired memory13,14 |
| C57BL/6 mice | 1 mg/kg daily for 4 days | 19d16,17 | TH neurons 36%16 and 40% ↓17 | 73% ↓ at day 1916 | Not assessed | Not assessed | Not assessed | Not assessed | |
| C57BL/6 mice | 2.5–5 mg/kg (once) | 2m25, (1–5m)23, 718,19,20,21,22,24,26,27, and 10m26 | TH neurons 18–22% ↓18,19,20,21,22,34, 50% ↓26 and 46% ↓27 | Not assessed | 2.2 and 1.7-fold ↑ α-syn protein in young and aged mice compared to age matched controls at 7 m20, 4-fold ↑ α-syn protein27 | ↓ voluntary movement in the open field27 and ↓ time in the rotarod test21,24,27 | ↑ α-syn expression in myenteric plexus23. 42% and 54% ↓ NE neurons in LC (7m, 10m), 28% ↓ Neun+ in motor cortex (7m) and 30% ↓ in hippocampus (10m)26 | ↑ gut permeability23 | |
| Rats | 5 mg/kg (once) | 15d28 | TH protein 50% ↓28 | Not assessed | Not assessed | Not assessed | Not assessed | Not assessed | |
| Intranasal (no studies for rats) | C57BL/6 mice | 1 mg/ml (every other day) | 21d32, 1m29,30,31, 5m33 | TH neurons 38–55%29,30,31, 79% ↓33 | ≈40% ↓33 | 2.229 and 2.4-fold30 in α-syn protein | ↓ voluntary movement in the open field29,30,33 and bradykinesia (pole test)30,31 | 44% ↓ in TH protein and 2.75-fold ↑ in α-syn protein in OB30, 31.9% ↓ in TH neurons in OB32, 1.75-fold ↑ in α-syn protein in OB33 | Not assessed |
Abbreviations: TH, tyrosine hydroxylase; SN, substantia nigra; OB, olfactory bulb; LC, locus coeruleus; NE, noradrenaline; α-syn, α-synuclein.
References: 1 (Chen et al., 2017); 2 (Wang et al., 2015c, Wang et al., 2015b, Wang et al., 2015a); 3 (He et al., 2016b, He et al., 2016a); 4 (Fu et al., 2015); 5 (Bao et al., 2018); 6 (Hritcu and Ciobica, 2013); 7 (Hritcu and Gorgan, 2014); 8 (Zheng et al., 2013b, Zheng et al., 2013a); 9 (Choi et al., 2009); 10 (Hunter et al., 2007); 11 (Hunter et al., 2017); 12 (Zheng et al., 2013b, Zheng et al., 2013a); 13(Zhang and Xu, 2018); 14 (Khan et al., 2018); 15 (Badshah et al., 2016); 16 (Beier et al., 2017), 17 (Bodea et al., 2014), 18 (Qin et al., 2007); 19(Qin et al., 2013); 20 (Zheng et al., 2013b, Zheng et al., 2013a); 21 (Liu et al., 2008); 22 (Reinert et al., 2014); 23Kelly et al., 2014; 24 (Jiang et al., 2017); 25 (Zheng et al., 2013b, Zheng et al., 2013a), 26 (Song et al., 2018); 27 (Chen et al., 2018; 28 (Gasparotto et al., 2018):29 (Li et al., 2015); 30 (He et al., 2016b, He et al., 2016a); 31 (Zheng et al., 2013b, Zheng et al., 2013a); 32 (Hasegawa-Ishii et al., 2017); 33 (He et al., 2013),34 (Qin et al., 2004); 35 (Gao et al., 2008).