Ontogeny of white matter, toll-like receptor expression, and motor skills in the neonatal ferret. Issue 70 (November 2018)

• Record Type: Journal Article
• Authors: Snyder, Jessica M.; Wood, Thomas R.; Corry, Kylie; Moralejo, Daniel H.; Parikh, Pratik; Juul, Sandra E.
• Is Part Of: International journal of developmental neuroscience. Issue 70(2018:Nov.)
• Page Start: 25
• Page End: 33
• Publication Date: 2018-11
• Subjects: Prematurity -- White matter injury -- Development -- Brain -- Central nervous system; Developmental neurobiology -- Periodicals; Neurology -- Periodicals; Neurologie du développement -- Périodiques; Developmental neurobiology; Periodicals; 612.8
• DOI: 10.1016/j.ijdevneu.2018.05.006
• Languages: English
• ISSNs: 0736-5748

Abstract

Highlights: Expression of PDFR✓, NG2, and Olig2 peak at P10–15 in the newborn ferret. In the ferret, myelin basic protein expression increases from P1 to P40. Myelin basic protein levels correspond with development of reflexes and gait. Toll-like receptor (TLR) 3 and 4 expression is low at birth, increasing by P40. LPS exposure followed by hypoxia/hyperoxia at P10 results in diffuse inflammation. Abstract: Inflammation caused by perinatal infection, superimposed with hypoxia and/or hyperoxia, appears to be important in the pathogenesis of preterm neonatal encephalopathy, with white matter particularly vulnerable during the third trimester. The associated inflammatory response is at least partly mediated through Toll-like receptor (TLR)-dependent mechanisms. Immunohistochemistry, gene expression, and behavioral studies were used to characterize white matter development and determine TLR3 and TLR4 expression and accumulation in the neonatal ferret brain. Expression of markers of white matter development increased significantly between postnatal day (P)1 and P10 (NG2, PDGFRα) or P15 (Olig2), and either remained elevated (NG2), or decreased again at P40 (PDGFRα, Olig2). Olig2 immunostaining within the internal capsule was also greatest at P15. Myelin basic protein (MBP) immunostaining and mRNA expression increased markedly from P15 to P40 and into adulthood, which correlated with increasing performance on behavioral tests (negative geotaxis, cliff aversion, righting reflex, and catwalk gait analysis). TLR4 and TLR3 positive staining was low at all ages, but TLR3 and TLR4 mRNA expression both increased significantly from P1 to P40. Following lipopolysaccharide (LPS) and hypoxia/hyperoxia exposure at P10, meningeal and parenchymal inflammation was seen, including an increase in TLR4 positive cells. These data suggest that the neuroinflammation associated with prematurity could be modeled in the newborn ferret.