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ISDN2014_0171: Dynamic and sex‐specific changes in DNA methylation during human fetal brain development
Author(s) -
Spiers H.,
Bray N.J.,
Han E.,
Schalkwyk L.C.,
Wong C.C.,
Pidsley R.,
Smith R.G.,
Mill J.
Publication year - 2015
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2015.04.142
Subject(s) - classics , theology , philosophy , history
We recently used cortical expression of the activity reporter gene zif268 to map the influence of age and quality of visual input on different visual field representations in area 17 of kittens. Here we screened for related proteomic changes in central and peripheral area 17 under normal visual stimulation (N) or binocular pattern deprivation for either two (2BD) or four (4BD) months from eye opening. Protein expression patterns were judged by means of a functional proteomics approach (2-D DIGE and mass spectrometry) and Western analysis. Additionally, BDNF mRNA expression was analyzed by means of qRT-PCR. Out of 44 proteins, compared to age-matched controls, 21 had a dysregulated expression in 2BD kittens and 9 in 4BD kittens. The BD affected proteins are associated with energy metabolism (n = 9), mRNA metabolism and transport (hnRNPL, hnRNPH), clathrin-mediated endocytosis (Hsc70, Endophilin), neurotransmitter release (Sept 5, -Synuclein) and outgrowth of neurites (CRMP4). When comparing 4BD to younger 2N animals, in central area 17, 12 of the investigated proteins did show an expression difference, whereas in peripheral area 17 such a difference occurred only for 1 protein. Interestingly, only in central area 17 of 2BD animals we observed higher BDNF mRNA levels. BDNF overexpression rescues the visual cortex from the maturational delay effect of dark rearing (Gianfranceschi et al., 2003). In central area 17, the high BDNF mRNA levels induced by the 1-hour light stimulation at the end of the BD period may activate a mechanism by which normal development is restored. Early onset BD seems to prevent the necessary developmental changes in protein expression more in the peripheral than in the central visual field representation. Both the light-induced zif268 activation patterns and this proteomic study underscore that early onset BD delays area 17 maturation and that this effect is stronger for peripheral area 17.