Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain, which persists into early adulthood.
Prenatal and early postnatal zinc deficiency impairs learning and memory and these deficits persist into adulthood. A key modulator in this process may be the NMDA receptor; however, effects of zinc deficiency on the regulation of NMDA receptor activity are not well understood. Female Sprague-Dawley rats were fed diets containing 7 (zinc deficient, ZD), 10 (marginally zinc deficient, MZD) or 25 (control) mg Zn/g diet preconception through postnatal day (PN) 20, at which time pups were weaned onto their maternal or control diet. Regulation of NMDA receptor expression was examined at PN2, PN11, and PN65. At PN2, expression of whole brain NMDA receptor subunits NR1, NR2A, and NR2B was lower in pups from dams fed ZD and MZD compared to controls, as analyzed using relative RT-PCR and immunoblotting. At PN11, whole brain and hippocampi NR1, NR2A, NR2B and PSA-NCAM (polysialic acid-neural cell adhesion molecule) expression and the number of PSA-NCAM immunoreactive cells were lower in pups from dams fed ZD compared to controls. Whole brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations were lower in pups from dams fed ZD or both low zinc diets, respectively. Whole brain NR1 expression remained lower in previously zinc-deficient rats at PN65. These data indicate potential mechanisms through which developmental zinc deficiency can impair learning and memory later in life.
Department of Nutrition, University of California, Davis, California 95161, USA.
Winyoo
W
Chowanadisai
Shannon L
SL
Kelleher
Bo
B
Lönnerdal
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005526:Food, Formulated; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D039842:Neural Cell Adhesion Molecule L1; D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D020932:Nerve Growth Factor; D015032:Zinc