Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.
Perinatal choline supplementation has produced several benefits in rodent models, from improved learning and memory to protection from the behavioral effects of fetal alcohol exposure. We have shown that supplemented choline through gestation and lactation produces long-term improvement in deficient sensory inhibition in DBA/2 mice which models a similar deficit in schizophrenia patients. The present study extends that research by feeding normal or supplemented choline diets to DBA/2 mice carrying the null mutation for the α7 nicotinic receptor gene (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at mating and remained on the specific diet until offspring weaning. Thereafter, offspring were fed standard rodent chow. Adult offspring were assessed for sensory inhibition. Brains were obtained to ascertain hippocampal α7 nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant for Chrna7 failed to show improvement in sensory inhibition. Only wildtype choline-supplemented mice showed improvement with the effect solely through a decrease in test amplitude. This supports the hypothesis that gestational-choline supplementation is acting through the α7 nicotinic receptor to improve sensory inhibition. Although there was a significant gene-dose-related change in hippocampal α7 receptor numbers, binding studies did not reveal any choline-dose-related change in binding in any hippocampal region, the interaction being driven by a significant genotype main effect (wildtype>heterozygote>null mutant). These data parallel a human study wherein the offspring of pregnant women receiving choline supplementation during gestation, showed better sensory inhibition than offspring of women on placebo.
Medical Research Service, Veterans Affairs Medical Center, Denver, CO, USA; Department of Psychiatry, University of Colorado, Anchutz Medical Campus, 12800 East 19th Avenue, Aurora, CO, USA. Electronic address: Karen.Stevens@ucdenver.edu.
Karen E
KE
Stevens
Medical Research Service, Veterans Affairs Medical Center, Denver, CO, USA.
Kevin S
KS
Choo
Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
Jerry A
JA
Stitzel
Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
Michael J
MJ
Marks
Medical Research Service, Veterans Affairs Medical Center, Denver, CO, USA; Department of Psychiatry, University of Colorado, Anchutz Medical Campus, 12800 East 19th Avenue, Aurora, CO, USA.
Catherine E
CE
Adams
D000161:Acoustic Stimulation; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002794:Choline / Q000494:pharmacology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007774:Lactation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011247:Pregnancy; D012559:Schizophrenia; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000032:analysis / Q000172:deficiency / Q000502:physiology*
D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002794:Choline
Chrna7 null mutation; DBA/2 mice; Gestational choline supplementation; Sensory gating; Sensory inhibition