Altered expression of key dopaminergic regulatory proteins in the postnatal brain following perinatal n-3 fatty acid dietary deficiency.
The consequences of maternal linolenic acid (LNA, 18:3n-3) dietary deficiency on key dopamine (DA)-associated regulatory proteins in mesolimbic and mesocortical structures of the postnatal rat brain have been investigated. A marked (4.5-fold) decrease of the DA-synthesizing enzyme tyrosine hydroxylase accompanied by a down-regulation (approx 7.5-fold) of the vesicular monoamine transporter (VMAT-2) and a depletion of VMAT-associated vesicles in the hippocampus were observed in deficient offspring compared with adequately fed controls. The DA transporter (DAT) was not affected by the LNA deficiency indicative of a DAT/VMAT-2 ratio increase that may enhance the risk of damage of the dopaminergic (DAergic) terminal. A robust increase in DA receptor (DAR1 and DAR2) levels was noticed in the cortex and striatum structures possibly to compensate for the low levels of DA in synaptic clefts. Microglia activation characterized by enhanced levels of ED1 antibody and nuclear internalization of p65 NFkappaB was noticed following LNA deficiency. Diminished levels of 22:6n-3 docosahexaenoic acid (Schiefermeier and Yavin 2002), the most ubiquitous metabolite generated by LNA is proposed to reduce the anti-oxidant arsenal in the developing brain and cause microglia activation and enhanced oxidative stress to increase the risk of certain DA-associated neurological disorders.
Kuperstein
Faina
F
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel, and Laboratory for Neuronal Cell Biology and Gene Transfer, Center for Human Genetics, Flanders Institute for Biotechnology (VIB), KU Leuven, Leuven, Belgium.
Eilam
Raya
R
Yavin
Ephrain
E
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D012333:RNA, Messenger; D011954:Receptors, Dopamine; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine