Effects of postnatal dietary choline supplementation on motor regional brain volume and growth factor expression in a mouse model of Rett syndrome.
Nutritional status during pregnancy and lactation can influence behavioral and anatomical characteristics of several neurological disorders in the offspring, including Rett syndrome (RTT). RTT is associated with mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCp2), a transcriptional repressor that binds methylated DNA. In Mecp2(1lox) mice, a model of RTT, enhancing maternal nutrition through choline supplementation attenuates motor coordination deficits in the mutant offspring. Here, we examine alterations in brain volume and growth factor expression in the cerebellum and striatum, motor regions that may contribute to the improved behavioral performance seen with choline supplementation. Mecp2(1lox) dams were given choline in drinking water, and pups nursed from birth to weaning. Brains of male offspring were collected at postnatal day 42 for volumetric and growth factor expression analyses. Compared to wild-type mice, Mecp2(1lox) null mice had decreased whole brain, cerebellar and striatal volume. Choline supplementation had no effect on brain volume. Nerve growth factor and insulin-like growth factor-1 expression was similar between wild-type and Mecp2(1lox) mice while brain derived neurotrophic factor was reduced in Mecp2(1lox) mice. Choline supplementation increased striatal nerve growth factor expression in wild-type and Mecp2(1lox) mice, suggesting that neuronal proliferation and survival may contribute to improved motor performance in this model of RTT.
Nag
Nupur
N
Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA.
Mellott
Tiffany J
TJ
Berger-Sweeney
Joanne E
JE
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002794:Choline / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism*; D018697:Nootropic Agents / Q000008:administration & dosage*; D015518:Rett Syndrome / Q000178:diet therapy / Q000235:genetics / Q000473:pathology
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D009414:Nerve Growth Factors; D018697:Nootropic Agents; D002794:Choline