Maternal micronutrient imbalance alters gene expression of BDNF, NGF, TrkB and CREB in the offspring brain at an adult age.
Micronutrients like folate, vitamin B12, and fatty acids which are interlinked in the one carbon cycle play a vital role in mediating epigenetic processes leading to an increased risk for neurodevelopmental disorders in the offspring. Our earlier study demonstrates that a micronutrient imbalanced diet adversely affects docosahexaenoic acid (DHA) and protein levels of neurotrophins like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain and cognition in the offspring by 3 months of age. In this study we attempt to analyze if these effects are a consequence of a change in gene expression of these molecules. Further, we also examined the effect of either a postnatal control diet or a prenatal omega-3 fatty acid supplementation on gene expression in the cortex of the offspring. Pregnant rats were divided into control and five treatment groups at two levels of folic acid (normal and excess folate) in the presence and absence of vitamin B12. Omega-3 fatty acid (eicosapentaenoic acid - EPA+DHA) supplementation was given to vitamin B12 deficient groups. Following delivery, 8 dams from each group were shifted to control diet and remaining continued on the same treatment diet. Our results demonstrate that the imbalanced diet caused a marked reduction in the mRNA levels of BDNF, NGF, TrkB, and cAMP response element-binding protein (CREB). Prenatal omega-3 fatty acid supplementation to the maternal imbalanced diet was able to normalize the mRNA levels of all the above genes. This study demonstrates that a maternal diet imbalanced in micronutrients (folic acid, vitamin B12) influences gene expression of neurotrophins and their signalling molecules and thereby adversely affects the brain of the offspring.
Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India.
Pratiksha
P
Sable
Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India.
Anvita
A
Kale
Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India.
Asmita
A
Joshi
Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune Satara Road, Pune 411043, India. Electronic address: srjoshi62@gmail.com.
Sadhana
S
Joshi
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D015525:Fatty Acids, Omega-3; D018977:Micronutrients; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D005492:Folic Acid
BDNF; CREB; Cognition; Micronutrient imbalance; NGF; TrkB