Next-Generation Sequencing Identifies Polyunsaturated Fatty Acid Responsive Genes in the Juvenile Rat Cerebellum

Overview

Journal Nutrients

Date 2019 Feb 17

PMID 30769946

Citations 1

Authors

Aaron A Mehus

Aaron M Dickey

Timothy P L Smith

Kathleen M Yeater

Matthew J Picklo

Affiliations

Soon will be listed here.

Abstract

Dietary -3 polyunsaturated fatty acids (PUFA) influence postnatal brain growth and development. However, little data exist regarding the impacts of dietary -3 PUFA in juvenile animals post weaning, which is a time of rapid growth. We tested the hypothesis that depleting dietary -3 PUFA would result in modifications to the cerebellar transcriptome of juvenile rats. To test this hypothesis, three week old male rats (an age that roughly corresponds to an 11 month old child in brain development) were fed diets containing either soybean oil (SO) providing 1.1% energy from α-linolenic acid (ALA; 18:3-3; ALA-sufficient) or corn oil (CO) providing 0.13% energy from ALA (ALA-deficient) for four weeks. Fatty acids (FAs) in the cerebellum were analyzed and revealed a 4-fold increase in n-6 docosapentaenoic acid (DPA; 22:5-6), increases in arachidonic acid (AA; 20:4-6) and docosatetraenoic acid (DTA; 22:4-6), but no decrease in docosahexaenoic acid (DHA; 22:6-3), in animals fed CO versus SO. Transcript abundance was then characterized to identify differentially expressed genes (DEGs) between the two diets. Upper quartile (UQ) scaling and transcripts per million (TPM) data normalization identified 100 and 107 DEGs, respectively. Comparison of DEGs from the two normalization methods identified 70 genes that overlapped, with 90% having abundance differences less than 2-fold. , a transcriptional activator that plays roles in neuroprotection and learning, was elevated over 2-fold from the CO diet. These data indicate that expression of in the juvenile rat cerebellum is responsive to dietary -3 PUFA, but additional studies are needed clarify the neurodevelopmental relationships between -3 PUFA and and the resulting impacts.

Citing Articles

Lipotoxic Injury Differentially Regulates Brain Microvascular Gene Expression in Male Mice.

Nuthikattu S, Milenkovic D, Rutledge J, Villablanca A Nutrients. 2020; 12(6).

PMID: 32545722 PMC: 7353447. DOI: 10.3390/nu12061771.

References

Zimmer L, Durand G, Guilloteau D, Bodard S, Besnard J, Chalon S . Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J Lipid Res. 2000; 41(1):32-40. View

Ntambi J, Bene H . Polyunsaturated fatty acid regulation of gene expression. J Mol Neurosci. 2001; 16(2-3):273-8; discussion 279-84. DOI: 10.1385/JMN:16:2-3:273. View

Kitajka K, Puskas L, Zvara A, Hackler Jr L, Barcelo-Coblijn G, Yeo Y . The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Natl Acad Sci U S A. 2002; 99(5):2619-24. PMC: 122397. DOI: 10.1073/pnas.042698699. View

Puskas L, Kitajka K, Nyakas C, Barcelo-Coblijn G, Farkas T . Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus. Proc Natl Acad Sci U S A. 2003; 100(4):1580-5. PMC: 149875. DOI: 10.1073/pnas.0337683100. View

Barcelo-Coblijn G, Kitajka K, Puskas L, Hogyes E, Zvara A, Hackler Jr L . Gene expression and molecular composition of phospholipids in rat brain in relation to dietary n-6 to n-3 fatty acid ratio. Biochim Biophys Acta. 2003; 1632(1-3):72-9. DOI: 10.1016/s1388-1981(03)00064-7. View

Barcelo-Coblijn G, Hogyes E, Kitajka K, Puskas L, Zvara A, Hackler Jr L . Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids. Proc Natl Acad Sci U S A. 2003; 100(20):11321-6. PMC: 208755. DOI: 10.1073/pnas.1734008100. View

Ten Donkelaar H, Lammens M, Wesseling P, Thijssen H, Renier W . Development and developmental disorders of the human cerebellum. J Neurol. 2003; 250(9):1025-36. DOI: 10.1007/s00415-003-0199-9. View

Kitajka K, Sinclair A, Weisinger R, Weisinger H, Mathai M, Jayasooriya A . Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression. Proc Natl Acad Sci U S A. 2004; 101(30):10931-6. PMC: 503722. DOI: 10.1073/pnas.0402342101. View

Calderon F, Kim H . Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004; 90(4):979-88. DOI: 10.1111/j.1471-4159.2004.02520.x. View

10.

Ponnio T, Conneely O . nor-1 regulates hippocampal axon guidance, pyramidal cell survival, and seizure susceptibility. Mol Cell Biol. 2004; 24(20):9070-8. PMC: 517886. DOI: 10.1128/MCB.24.20.9070-9078.2004. View

11.

DeMar Jr J, Ma K, Bell J, Rapoport S . Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. J Neurochem. 2004; 91(5):1125-37. DOI: 10.1111/j.1471-4159.2004.02789.x. View

12.

Cao D, Xue R, Xu J, Liu Z . Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures. J Nutr Biochem. 2005; 16(9):538-46. DOI: 10.1016/j.jnutbio.2005.02.002. View

13.

Kuperstein F, Yakubov E, Dinerman P, Gil S, Eylam R, Salem Jr N . Overexpression of dopamine receptor genes and their products in the postnatal rat brain following maternal n-3 fatty acid dietary deficiency. J Neurochem. 2005; 95(6):1550-62. DOI: 10.1111/j.1471-4159.2005.03513.x. View

14.

Pearen M, Ryall J, Maxwell M, Ohkura N, Lynch G, Muscat G . The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle. Endocrinology. 2006; 147(11):5217-27. DOI: 10.1210/en.2006-0447. View

15.

Kothapalli K, Anthony J, Pan B, Hsieh A, Nathanielsz P, Brenna J . Differential cerebral cortex transcriptomes of baboon neonates consuming moderate and high docosahexaenoic acid formulas. PLoS One. 2007; 2(4):e370. PMC: 1847718. DOI: 10.1371/journal.pone.0000370. View

16.

Fu Y, Luo L, Luo N, Zhu X, Garvey W . NR4A orphan nuclear receptors modulate insulin action and the glucose transport system: potential role in insulin resistance. J Biol Chem. 2007; 282(43):31525-33. DOI: 10.1074/jbc.M701132200. View

17.

Pearen M, Myers S, Raichur S, Ryall J, Lynch G, Muscat G . The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle. Endocrinology. 2008; 149(6):2853-65. DOI: 10.1210/en.2007-1202. View

18.

Liu J, Almaguel F, Bu L, Leon D, De Leon M . Expression of E-FABP in PC12 cells increases neurite extension during differentiation: involvement of n-3 and n-6 fatty acids. J Neurochem. 2008; 106(5):2015-29. PMC: 2785489. DOI: 10.1111/j.1471-4159.2008.05507.x. View

19.

Belkind-Gerson J, Carreon-Rodriguez A, Contreras-Ochoa C, Estrada-Mondaca S, Parra-Cabrera M . Fatty acids and neurodevelopment. J Pediatr Gastroenterol Nutr. 2008; 47 Suppl 1:S7-9. DOI: 10.1097/MPG.0b013e3181818e3f. View

20.

Maekawa M, Takashima N, Matsumata M, Ikegami S, Kontani M, Hara Y . Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses. PLoS One. 2009; 4(4):e5085. PMC: 2663848. DOI: 10.1371/journal.pone.0005085. View