Postnatal dietary choline supplementation alters behavior in a mouse model of Rett syndrome.
Rett syndrome (RTT), a neurodevelopmental disorder primarily affecting females, is accompanied by behavioral and neuropathological abnormalities and decreases in brain cholinergic markers. Because the cholinergic system is associated with cognitive and motor functions, cholinergic deficits in RTT may underlie some of the behavioral abnormalities. In rodents, increased choline availability during development enhances transmission at cholinergic synapses and improves behavioral performance throughout life. We examined whether choline supplementation of nursing dams would attenuate deficits in Mecp2(1lox) offspring, a mouse model of RTT. Dams were given choline in drinking water, and pups nursed from birth to weaning. Offspring were assessed on development and behavior. In Mecp2(1lox) males, choline supplementation improved motor coordination and locomotor activity, whereas in females it enhanced grip strength. Choline supplementation did not improve response to fear conditioning. Postnatal choline supplementation attenuates some behavioral deficits in Mecp2(1lox) mice and should be explored further as a therapeutic agent in RTT.
Nag
Nupur
N
Department of Biological Sciences, Wellesley College, Wellesley, MA 02481, USA.
Berger-Sweeney
Joanne E
JE
D000109:Acetylcholine / Q000096:biosynthesis; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002794:Choline / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005526:Food, Formulated; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018908:Muscle Weakness / Q000188:drug therapy / Q000209:etiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D015518:Rett Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D016896:Treatment Outcome
D002794:Choline; D000109:Acetylcholine