. 2022 May 6;81(6):414–433. doi: 10.1093/jnen/nlac028

TABLE 3.

Summary of Effects of Azetidine Exposure in Adult and Neonatal Mice

Experiment	Clinical Disease (600 mg/kg group only)	OL Nucleomegaly and Nuclear Clearing (LM, EM)	OL Apoptosis (TUNEL, Caspase-3 IHC)	WM Microglial Reaction/Nodules (Iba-1 IHC)	OL ER stress/UPR		↑MHC 1 on Apoptotic OL (IHC)	WM Myelin Blistering and Myelinosomes (MBP IHC)	Dystrophic WM Axons (LM, Biel)	Liver Abnormalities (LM)
Experiment	Clinical Disease (600 mg/kg group only)	OL Nucleomegaly and Nuclear Clearing (LM, EM)	OL Apoptosis (TUNEL, Caspase-3 IHC)	WM Microglial Reaction/Nodules (Iba-1 IHC)	Nuclear translocation of UPR proteins (IHC)	Dilated ER, autophagy/mitophagy (EM)	↑MHC 1 on Apoptotic OL (IHC)	WM Myelin Blistering and Myelinosomes (MBP IHC)	Dystrophic WM Axons (LM, Biel)	Liver Abnormalities (LM)
A1 (adult mice)	+^†	+^†	+^†	+^†	+^†		+^†	+	+^†	+^†
A2 (adult mice)	−	+	ND	+	ND	+	ND	ND	ND	+^†
N1 pups^*	−	+	ND	ND	ND	ND	ND	ND	ND	+^‡
N1 dams^*	−	+	ND	ND	ND	ND	ND	ND	ND	+
N2 pups	−	+	+^§	ND	ND	ND	+	ND	ND	+
N2 dams	−	+	+	ND	ND	ND	ND	−	ND	+

Biel, Bielschowsky silver impregnation; EM, electron microscopy; ER, endoplasmic reticulum; IHC, immunohistochemistry; LM, light microscopy; MBP, myelin basic protein; ND, not done; OL, oligodendrocyte; UPR, unfolded protein response; WM, white matter; +, present; −, analysis performed with negative results.

Treatment PO-initiated postweaning with 350 mg/kg Aze resulted in no definite effects on the CNS by routine LM analysis.

^†

Aze dose-dependent effects.

^‡

Increased frequency in pups with longer exposures to Aze.

^§

Greater incidence of OL apoptosis in Aze-treated pups versus dams.