Pregnancy modulates precursor cell proliferation in a murine model of focal demyelination

• Published in: Neuroscience 2010-05, Vol.167 (3), p.656-664
• Main Authors: Haddady, S, Low, H.P, Billings-Gagliardi, S, Riskind, P.N, Schwartz, W.J
• Format: Article
• Language: English
• Subjects: Animals; Antigens - metabolism; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological and medical sciences; Bromodeoxyuridine; Cell Lineage - physiology; Cell Proliferation; Central Nervous System - metabolism; Central Nervous System - pathology; Central Nervous System - physiopathology; Corpus Callosum - drug effects; Corpus Callosum - metabolism; Corpus Callosum - pathology; Demyelinating Diseases - chemically induced; Demyelinating Diseases - metabolism; Demyelinating Diseases - physiopathology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Histones - metabolism; Lysophosphatidylcholines - toxicity; Mice; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - pathology; Nerve Regeneration - physiology; Neurology; Oligodendroglia - cytology; Oligodendroglia - metabolism; Pregnancy - metabolism; Proteoglycans - metabolism; Stem Cells - cytology; Stem Cells - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.02.061

Abstract In mice, pregnancy has been shown to have a beneficial effect on the endogenous repair of focal lysolecithin-induced CNS demyelinative lesions, enhancing the genesis of new oligodendrocytes and the degree of remyelination. To identify local cells undergoing mitosis in response to such lesions, we examined the time course of phospho-histone H3 (PH3) and myelin basic protein (MBP) expression by immunohistochemistry. After lysolecithin injection into the corpus callosum of virgin female mice, the number of dividing cells peaked about 48 h after injection and declined gradually to baseline by day 7; in pregnant mice, this initial peak was unchanged, but a new delayed peak on day 4 was induced. Colocalization data using PH3 and NG2 proteoglycan, or bromodeoxyuridine (BrdU) and oligodendrocyte transcription factor 1 (Olig1), suggested that about 75% of the proliferating cells on day 2, and about 40% of the cells on day 4, were likely of oligodendrocyte lineage; these differential percentages were of the same magnitude in both virgin and pregnant animals. Notably, the heightened proliferative response to focal lysolecithin injection during pregnancy was specific to gestational stage (early, but not late) and to lesion location (in the corpus callosum of the periventricular forebrain, but not in the caudal cerebellar peduncle of the hindbrain).