. Author manuscript; available in PMC: 2014 Jul 1.

Published in final edited form as: Neurosci Biobehav Rev. 2013 Jan 10;37(6):1120–1138. doi: 10.1016/j.neubiorev.2013.01.007

Table 1.

Animal models of Tourette syndrome based on increased brain immune mediators (spontaneous or induced).

Exposure	Controls/ comparator s	Route of exposure	Species	Strain	Agent of BBB breach	Pathologic findings	Behavior abnormalities	Citation
BTBR T+tf/J (BTBR) mice	C57BL/6J (B6) mice BTBR × B6 F1 mice	NA¹	Mouse	BTBR	NA	↑ serum anti-brain antibodies ↑ IgG and IgE deposits in brain Brain region-dependent ↑ in IL- 1β, IL-6, IL-10, IL-12, IL-18, IL- 33 and IFN-γ	↑ self-grooming ↑ marble burying, bar-biting ↓ interaction with novel social partner vs. novel object	McFarlane et al., 2008; Heo et al., 2011; Pearson et al., 2011; Amodeo et al., 2012
IL-2, mid- gestation	Vehicle (PBS)	ip	Mouse	SJL/J	None	[¹²⁵I] IL-2 injected into mothers crossed the placenta	↑ self-grooming ↑ rearing ↓ conditioned eyeblink acquisition	Ponzio et al., 2007
IL-6, mid- gestation	IL1-α, TNF- α, or IFN-γ, or vehicle (PBS)	ip	Mouse	C57BL/6J	None	↑ expression of α, β and γ crystallin genes in fetal brain	↓ PPI ↓ latent inhibition	Smith et al., 2007; Garbett et al., 2012
IL-2 IL-6	IL-1β or vehicle (PBS)	ip	Mouse	Balb/cCR	None	IL-2: ↑ DA activity in prefrontal Cx ↑ NE activity in Hc, HYP IL-6: ↑ DA activity in prefrontal Cx, Hc ↑ 5-HT activity in prefrontal Cx, Hc	IL-2: ↑ digging, rearing ↑ investigation of novel object IL-6: ↑ digging, rearing ↑ grooming	Zalcman et al., 1994; Zalcman et al., 1998
TGF-β1 overexpressi on (viral vector)	β-galactosida se overexpres sion (viral vector)	Hc injection, age 2 or 8 weeks	Mouse	C57BL/6J	NA	Early: Chronic ↓ TGF-β1 mRNA in Hc Adult: Transient ↓ MCP-1 mRNA in Hc but no persistent changes	Early: ↑ self-grooming ↑ forced swim test immobility Adult: ↓ self-grooming ↓ forced swim test immobility	Depino et al., 2011
sIL-2Rα sIL-2Rβ	sIL-1R1 Vehicle (PBS)	sc	Mouse	Male Balb/cCR	None	sIL-2Rα: ↑ c-fos immunoreactivity and sIL-2Rα deposits in STR and motor, infralimbic and cingulate Cx sIL-2Rβ: ↑ c-fos immunoreactivity and sIL-2Rβ deposits in STR and motor, infralimbic, cingulate and prepyriform Cx	sIL-2Rα: ↑ rearing, turning ↑ grooming ↑ head bobbing, jumping sIL-2RB:↑ rearing, turning ↑ grooming ↑ head bobbing, jumping ↑ horizontal stereotypic and ambulatory movements	Zalcman et al. 2012
sIL-6Rα	Vehicle/tes t stress Uninjected/ no test stress	sc	Mouse	Male Balb/cCR	None	↑ sIL-6Rα in STR, motor and infralimbic Cx, ventral nuclei of thalamus gp130 colocalized with sIL-6Rα in brain	↑ rearing, turning ↑ head bobbing ↑ horizontal ambulation ↑ vertical stereotypic movements	Patel et al., 2012

Key: 5-HT, serotonin; BBB, blood-brain barrier; Cx, cortex; DA, dopamine; Hc, hippocampus; HYP, hypothalamus; IL, interleukin; ip, intraperitoneal; NE, norepinephrine; PBS, phosphate-buffered saline; PPI, prepulse inhibition; s, soluble; sc, subcutaneous; STR, striatum

NA, not applicable