TABLE 1.

Summary of Azetidine Treatment Groups and Analyses Performed

Experiment	Aze Dose (mg/kg)	Treatment		Treatment Duration	Analyses Performed	Non-CNS Tissues
		IP	PO
A1 (adult mice)	0, 300, 600	QD (5 mice/group)	QD (n = 5 mice/group)	Up to 4 weeks*	LM† TUNEL IHC‡	+
A2 (adult mice)	0, 300, 600	5×/week (3–4 mice/group)	—	Up to 4 weeks	EM, IHC¶	+
N1 pups	0, 350	—	3×/week (n = 37 total)	D23 (postweaning) to D44	LM†	+
N1 dams	0, 350	—	3×/week (n = 3/group)	5 weeks (postbirth)	LM†	+
N2 pups	0, 300	—	3×/week (n = 5/group)	E14 to D22 (weaning) to 6 weeks	LM†, TUNEL, Caspase 3 IHC	+§
N2 dams	0, 300	—	3×/week (n = 2/group)	E14 to 5 weeks postbirth	LM†, TUNEL, Caspase 3 IHC	+§

LM, light microscopy; EM, electron microscopy; IHC immunohistochemistry; TUNEL, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling; +, tissues sampled.

^*Excludes mice that died or were euthanized in the 600 mg/kg group.

^†LM, Light microscopy: H&E, Luxol fast blue, Bielschowsky.

^‡IHC, immunostained with antibodies listed in Table 2.

^§Samples include eyes and optic nerves.

^¶Iba-1 IHC only.