Region-specific susceptibilities to cuprizone-induced lesions in the mouse forebrain: Implications for the pathophysiology of schizophrenia.
Cuprizone (CPZ) is a neurotoxic agent acting as a copper chelator. In our recent study, C57BL/6 mice given dietary CPZ (0.2%) showed impairments in spatial working memory, social interaction, and prepulse inhibition. These abnormalities are reminiscent of certain schizophrenia symptoms and are not likely due to damage in the whole brain or in any single white matter tract/brain region. We hypothesized that white matter damage resulting from CPZ-treatment may be site-specific rather than universal. We examined the forebrains of C57BL/6 mice given the CPZ-containing diet and compared them with those of controls. We assessed CPZ-induced demyelination in main white matter tracts of the forebrain, evaluated myelin break down in the neuropil of the main olfactory bulb (MOB), cerebral cortex (CTX), caudate putamen (CP), hippocampus (HP), thalamus (TH), and hypothalamus (HY), and counted the number of myelin sheath forming oligodendrocytes (OLs) in CTX, CP, TH, and HY. Obvious demyelination was observed in the corpus callosum, external capsule, CP, and dorsal hippocampal commissure whereas other tracts seemed to be unaffected. The neuropil of CTX, HP and MOB showed myelin break down, which was mild in TH and HY. The number of OLs was decreased in all the above regions of CPZ-treated mice although the degree of OL loss was not consistent across regions. The data provide further support for white matter abnormalities contributing to schizophrenia-like behaviors in mice.
Yang
Hong-Ju
HJ
Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, 1135 Lincoln Dr., Carbondale, IL 62901, USA.
Wang
Haitao
H
Zhang
Yanbo
Y
Xiao
Lan
L
Clough
Richard W
RW
Browning
Ronald
R
Li
Xin-Min
XM
Xu
Haiyun
H
D000821:Animal Feed; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D002614:Chelating Agents / Q000378:metabolism / Q000633:toxicity*; D003300:Copper / Q000378:metabolism; D003471:Cuprizone / Q000378:metabolism / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D019581:Neuropil / Q000187:drug effects / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012559:Schizophrenia / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology
D002614:Chelating Agents; D003471:Cuprizone; D003300:Copper