Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats:critical role of developmental stage

• DOI: 10.1194/jlr.m200132-jlr200
• Publication Date: 2020-02-24T18:31:07Z
• Authors: Ercem Kodas; Sylvie Vancassel; Bernard Lejeune; Denis Guilloteau; Sylvie Chalon
• Keywords: Neurochemical

Previous investigations have shown that the lipid composition of cerebral membranes and dopaminergic neurotransmission are changed under chronic α-linolenic acid diet deficiency in rat. This study investigated whether these changes could be reversed if stage brain maturation might play a role recovery process. The effects reversion on fatty (FA) were studied regions known to affected by such (i.e., prefrontal cortex nucleus accumbens) 2-month-old animals. Dopamine release pharmacological stimulation was using dual-probe microdialysis method. Vesicular monoamine transporters quantitative autoradiography. reversal diet, with adequate levels n-6 n-3 polyunsaturated acids (PUFAs), given deficient rats at different stages development (0, 7, 14, or 21 days age). results showed when during lactating period, this able restore both FA parameters studied. 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Perinatal later life.Nat. 7: 258-259Crossref (126) establish links between we two deficiency, i.e., (PFCx) (NAcc), (DA) tyramine method awake vesicular transporter (VMAT2) binding sites autoradiography [3H]dihydrotetrabenazine NAcc. began development, 0, age. Our hypothesis degree recover Two generations Wistar originating Laboratoire Nutrition Sécurité Alimentaire (INRA, Jouy-en-Josas, France) fed containing 6% fat form African peanut oil specifically already described provided 1,200 mg less than per 100 g diet. before mating, second generation divided groups. first group received (deficient) replaced mixture 60% 40% rapeseed (control). control same amount 200 (n-6/n-3 = 6), previously maternal (37Guesnet pregnancy lactation serum rat.Reprod. 275-292Crossref (30) overall diets summarized Tables 1 2. number females four groups, each receiving instead stages: day parturition parturition. Dietary groups named D0, D7, D14, D21 Fig. 1. At progeny respective dams. All available ad libitum. Experiments 2 month old six Four litters used group, total 24 study. Each litter mean five rats, mixed weaning. For study, average 18 108 animals experimental procedures compliance guidelines European Community Commission directives 86/609/EEC.TABLE 1.Diet compositionControln-3 Deficientg/kgCasein220220DL methionine1.61.6Corn starch432.4432.4Saccharose216216Cellulose2020Mineral mixtureaaComposition (g/kg mineral mixture): CaHPO4·2H2O, 380; K2HPO4, 240; CaCO3, 180; NaCl, 69; MgO, 20; MgSO4·7H2O, 90; FeSO4·7H2O, 8.6; ZnSO4·H2O, 5; MnSO4·H2O, CuSO4·5H2O, 1; NaF, 0.8; CrK(SO4)2·12H2O, 0.5; (NH4)6Mo7O24·4H2O, 0.02; KI, 0.04; CoCO3, Na2SeO3, 0.02.4040Vitamin mixturebbComposition vitamin supplement triturated dextrose (mg/kg retinyl acetate (UI), 500,000; cholecalciferol 250,000; dl-alpha-tocopherol 5,000; menadione 100; thiamine HCl 1,000; riboflavine, nicotinic acid, 4,500; D-calcium panthotenate, 3,000; pyridoxine HCl, inositol, D-biotin, folic 200; cyanocobalamin, 1.35; L-ascorbic 10,000; paraamino-benzoic choline chlorhydrate, 75,000.1010OilsccTotal lipids: g/100 diet.Peanut23.660Rapeseed36.4–a aComposition 0.02.b bComposition 75,000.c cTotal Open table new tab TABLE 2.Fatty lipidsFatty AcidsaaAbbreviations used: SFA, saturated acids; MUFA, monounsaturated PUFA, acids.ControlbbAfrican (60.5%:39.5%).n-3 DeficientccAfrican oil.mg/100 acids16:08.19.918:02.43.120:00.91.222:01.21.824:00.60.8SFA13.216.816:1n-71.10.018:1n-960.960.818:1n-70.00.020:1n-91.11.1MUFA63.161.918:2n-621.221.3n-6 PUFA21.221.318:3n-33.6<0.1n-3 PUFA3.6<0.1n-6 + n-324.821.3n-6/n-35.9–PUFA, mg/100 diet18:2n-61196120118:3n-3203<6Oils kindly Lesieur-Alimentaire (Coudekerque; France).a aAbbreviations acids.b bAfrican (60.5%:39.5%).c cAfrican oil. Oils France). Five sacrificed decapitation. PFCx NAcc rapidly dissected ice, weighed, frozen liquid nitrogen, stored −80°C until use. homogenized Polytron Kinematica PT 1200 (Bioblock Scientific, Strasbourg, 5 ml chloroform-methanol solution 2:1 (v/v) presence butylhydroxy-toluene (0.002 g/l). Total extracted procedure Folch (38Folch Lees Sloane-Stanley simple isolation purification tissues.J. Biol. Chem. 1957; 226: 497-506Abstract To assess effectiveness quantify FAs, diheptadecanoyl (17:0) phosphatidylcholine (Sigma, St Quentin Fallavier, added internal standard prior extraction represented approximately 10% estimated FAs. Aliquots analytical quantification classes. three main classes (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylserine, PS) separated silica gel cartridge (BAKERBOND spe™ Amino, Baker, Phillipsburg, NJ) adapted Pietsch Lorentz (39Pietsch R.L. Rapid separation single aminopropyl cartridge.Lipids. 945-947Crossref (57) Briefly, isopropanol/chloroform (1:2) eluted neutral extract deposited beforehand cartridge. diethylether/acetic (98:2) free acetonitrile/n-propanol (4:1) PC. PE (1:1) acetone. PS isopropanol/methanol (4:1). then transmethylated boron trifluoride (Fluka, Socolab, Paris, 90°C 20 min Morisson Smith (40Morisson W. Preparation methyl esters dimethylacetals trifluoride-methanol.J. 1964; 5: 600-608Abstract class determined GLC (41Guesnet Alasnier Alessandri Modifying content determine requirements fetal suckling 1997; 32: 527-534Crossref (38) expressed percentage (wt %). Rats (n 7–8 group) anesthetized ketamine dose 150 mg/kg i.p. (Imalgène, Rhône Mérieux, placed stereotaxic apparatus (Stoelting, Wood Dale, IL). Body temperature maintained 37 ± 1°C surgery time thermostatically heating blanket (CMA 150, CMA/Microdialysis, Stockholm, Sweden). skull exposed holes drilled. Guide cannulas implanted atlas Paxinos Watson (42Paxinos Rat Stereotaxic Coordinates. Academic New York, NY1986Google left coordinates antero-posterior 5.2, lateral −0.6, dorso-ventral −1.8 mm, tilt 26° angle (MAB 14 G, Sweden) 1.7, −1.2, −6.4 mm CMA/Microdialysis) Bregma. anchored stainless-steel screw dental cement. Microdialysis probes length 3, 15 kDa molecular mass cut-off) 1, slowly lowered through guide cannula. Animals housed cylindrical Plexiglas cages (diameter 40 cm, height 32 cm), served home experiments, counterbalance arm holding swivel. They postoperatively overnight libitum access water diets. After implantation, immediately continuously perfused Dulbecco's buffer modified (ICN, Costa Mesa, CA) supplemented 2.2 mM CaCl2 1.1 MgCl2 (pH 7.4) 0.8 μl/min microsyringe pump (Harvard Apparatus, South Natick, MA). postoperative (22 h), flow rate increased 1.2 h experiment equilibrium reached. Dialysates collected intervals vials preloaded μl 0.1 M perchloric resulting sampling volume 29 μl. microinjection mounted syringes, perfusion alone (for NAcc) St. Louis, MO). Tyramine freshly dissolved use infused locally via probes. 80 dialysis alone, switching syringes time. contained 600 μM tyramine, respectively. Perfusion continued end experiment. baseline value released DA obtained averaging samples, values subsequent samples percentages baseline. pentobarbital bolus (Sanofi, Libourne, France), localization macroscopically checked sections. measured dialysates chromatography (HPLC) electrochemical detection Concorde (Waters, Quentin-Yvelines, Samples injected Rheodyne 7725i injector valve injection loop. mobile phase consisting 7% acetonitrile, 3% methanol, 90% citric mM, 10 monobasic phosphate sodium, 3.25 octanesulfonic heptanesulfonic EDTA, KCl, ml/liter o-phosphoric diethylamine pH adjusted pumped 0.3 ml/min Gold 118 system (Beckman, Fullerton, CA). Separation μm C18, 3.2 × column (LC-22C, BAS, West Lafayette, IN). glassy carbon working electrode set 800 mV reference situ Ag/AgCl detect compounds. Signals recorded quantified Beckman integrator. Amounts calculated comparing peak those external standards. Under conditions, limit fmol/μl. experiments. Brains removed ice (−35°C) dry ice-cooled isopentane storage −80° Twenty-micron thick coronal sections cut −20°C o