Interesterified fat maternal consumption before conception programms memory and learning of adulthood offspring: How big is this deleterious repercussion?

In recent years, interesterified fat (IF) has largely replaced trans fat in industrialized food. Studies of our research group showed that IF consumption may not be safe for central nervous system (CNS) functions. Our current aim was to evaluate IF maternal consumption before conception on cognitive performance of adult rat offspring. Female Wistar rats were fed with standard chow plus 20% soybean and fish oil mix (control group) or plus 20% IF from weaning until adulthood (before mating), when the diets were replaced by standard chow only. Following the gestation and pups' development, locomotion and memory performance followed by neurotrophin immunocontent and fatty acids (FA) profile in the hippocampus of the adulthood male offspring were quantified. Maternal IF consumption before conception decreased hippocampal palmitoleic acid incorporation, proBDNF and BDNF levels, decreasing both exploratory activity and memory performance in adult offspring. Considering that, the adult male offspring did not consume IF directly, further studies are needed to understand the molecular mechanisms and if the IF maternal preconception consumption could induce the epigenetic changes observed here. Our outcomes reinforce an immediate necessity to monitor and / or question the replacement of trans fat by IF with further studies involving CNS functions.

Interesterified fat consumption since gestation decreases striatal dopaminergic targets levels and gdnf impairing locomotion of adult offspring.

Interesterified fat (IF) currently substitutes the hydrogenated vegetable fat (HVF) in processed foods. However, the IF consumption impact on the central nervous system (CNS) has been poorly studied. The current study investigated connections between IF chronic consumption and locomotor impairments in early life period and adulthood of rats and access brain molecular targets related to behavior changes in adulthood offspring. During pregnancy and lactation, female rats received soybean oil (SO) or IF and their male pups received the same maternal supplementation from weaning until adulthood. Pups' motor ability and locomotor activity in adulthood were evaluated. In the adult offspring striatum, dopaminergic targets, glial cell line-derived neurotrophic factor (GDFN) and lipid profile were quantified. Pups from IF supplementation group presented impaired learning concerning complex motor skill and sensorimotor behavior. The same animals showed decreased locomotion in adulthood. Moreover, IF group showed decreased immunoreactivity of all dopaminergic targets evaluated and GDNF, along with important changes in FA composition in striatum. This study shows that the brain modifications induce by IF consumption resulted in impaired motor control in pups and decreased locomotion in adult animals. Other studies about health damages induced by IF consumption may have a contribution from our current outcomes.

Trans fat intake during pregnancy or lactation increases anxiety-like behavior and alters proinflammatory cytokines and glucocorticoid receptor levels in the hippocampus of adult offspring.

Changes in dietary habits, including the increased consumption of processed foods, rich in trans fatty acids (TFA), have profound effects on offspring health in later life. Thus, this study aimed to assess the influence of maternal trans fat intake during pregnancy or lactation on anxiety behavior, as well as markers of inflammation, oxidative stress, and expression of glucocorticoid receptors (GR) of adult male offspring. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0 g/kg body weight) during pregnancy or lactation. After weaning, male offspring received only standard diet. On the postnatal day 60, anxiety-like symptoms were assessed, the plasma was collected for the quantification of cytokines levels and the hippocampus removed for biochemical and molecular analysis. Our findings have evidenced that offspring from HVF-supplemented dams during pregnancy or lactation showed significantly greater levels of anxiety behavior. HVF supplementation increased plasma levels of proinflammatory cytokines and these levels were higher in the lactation period. In contrast, HVF supplementation decreased plasma levels of IL-10 in relation to SO/FO in both periods. Biochemical evaluations showed higher reactive species generation, protein carbonyl levels and catalase activity in offspring from HVF-supplemented dams during lactation. In addition, offspring from HVF-supplemented dams showed decreased GR expression in both supplemented periods. Together, these data indicate that consumption of TFA in different periods of development may increase anxiety-like behavior at least in part via alterations in proinflammatory and anti-inflammatory cytokine levels and GR expression in limbic brain regions.

Omega-3 decreases D1 and D2 receptors expression in the prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats.

Amphetamine (AMPH) abuse is a serious public health problem due to the high addictive potential of this drug, whose use is related to severe brain neurotoxicity and memory impairments. So far, therapies for psychostimulant addiction have had limited efficacy. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have shown beneficial influences on the prevention and treatment of several diseases that affect the central nervous system. Here, we assessed the influence of fish oil (FO), which is rich in n-3 PUFA, on withdrawal and relapse symptoms following re-exposure to AMPH. Male Wistar rats received d,l-AMPH or vehicle in the conditioned place preference (CPP) paradigm for 14 days. Then, half of each experimental group was treated with FO (3 g/kg, p.o.) for 14 days. Subsequently, animals were re-exposed to AMPH-CPP for three additional days, in order to assess relapse behavior. Our findings have evidenced that FO prevented relapse induced by AMPH reconditioning. While FO prevented AMPH-induced oxidative damages in the prefrontal cortex, molecular assays allowed us to observe that it was also able to modulate dopaminergic cascade markers (DAT, TH, VMAT-2, D1R and D2R) in the same brain area, thus preventing AMPH-induced molecular changes. To the most of our knowledge, this is the first study to show a natural alternative tool which is able to prevent psychostimulant relapse following drug withdrawal. This non-invasive and healthy nutraceutical may be considered as an adjuvant treatment in detoxification clinics.

Mediterranean X Western based diets: Opposite influences on opioid reinstatement.

Opioids are addictive drugs, whose misuse evoke withdrawal and relapse. Mediterranean-based diet (MBD) is rich in n-3 polyunsaturated fatty acids (PUFA), while Western based diets (WBDs) contain saturated fatty acids including interesterified fat (IF) and palm oil (PO), influencing neural functions. We compared MBD and WBDs on morphine-induced addiction parameters. Rats fed with MBD (chow plus 20% soybean- and fish-oil- n-6/n-3 PUFA 1:1) or WBD (WBD- PO or WBD-IF: chow plus 20% of palm oil or interesterified fat, respectively; high n-6/n-3 PUFA ratio) were exposed to morphine in conditioned place preference (CPP) paradigm. Anxiety-like behavior, locomotion and thermal sensitivity were evaluated during withdrawal. After morphine-CPP extinction, animals were challenged to morphine-reinstatement to induce relapse. All groups showed morphine-CPP, WBDs favored anxiety-like behaviors per se, locomotor sensitization and thermal hipersensitivity during withdrawal, resulting in increased morphine-reinstatement in comparison to MBD, which did not show relapse. WBDs increased glucocorticoid receptor immunoreactivity in the pre-frontal cortex, increasing corticosterone (CORT) and adrenocorticotrophic hormone (ACTH) per se and after morphine-reinstatement. In the nucleus accumbens, WBDs increased dopamine transporter (DAT) and dopamine receptor-2 (D2R) immunoreactivity and decreased dopamine receptor-1 (D1R). These findings indicate that WBDs facilitate morphine-reinstatement, unlike MBD, preserving the DA system mesolimbic neuroplasticity.

Modafinil reduces amphetamine preference and prevents anxiety-like symptoms during drug withdrawal in young rats: Involvement of dopaminergic targets in VTA and striatum.

Drug abuse and addiction are overwhelming health problems mainly during adolescence. Based on a previous study of our research group, the rats that received modafinil (MD) during the adolescence showed less preference for amphetamine (AMPH) in adulthood. Our current hypothesis is that MD will show beneficial effects against AMPH preference and abstinence symptoms during adolescence, a critical lifetime period when drug hedonic effects are more pronounced. We investigated the influence of MD pretreatment on AMPH preference in conditioned place preference (CPP) paradigm in adolescent rats and anxiety-like symptoms during drug withdrawal (48 h after the last AMPH dose) in elevated plus maze (EPM) task. Besides that, oxidative and molecular status were evaluated in the ventral tegmental area (VTA) and striatum. Our findings showed, as it was expected, that adolescent animals developed AMPH preference together with anxiety-like symptoms during the drug withdrawal while the MD pretreatment prevented those behaviors. Besides promoting benefits on reward parameters, MD was able to preserve VTA and striatum from oxidative damages. This was observed by the increased catalase activity and reduced generation of reactive species and lipid peroxidation, which were inversely modified by AMPH exposure. At molecular level, MD exerted an interesting modulatory activity on the VTA and induced an up-regulation in striatal dopaminergic targets (TH, DAT, D1R and D2R). So far, during the adolescence, MD presented beneficial behavioral outcomes that could be attributed to its modulatory activity on the striatal dopaminergic system in an attempt to maintain the adequate dopamine levels.

Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on Oral Dyskinesia in Rats.

Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg-1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.

Could Modafinil Prevent Psychostimulant Addiction? An Experimental Study in Rats.

Addiction is a serious health problem which leads to general social impairment. The period of adolescence plays a significant role in drug abuse liability. Psychostimulants, such as modafinil (MOD), are majorly used by teenagers seeking improvements in cognition, which contributes to its indiscriminate use. This study aimed to investigate the influence of MOD (64 mg/kg by gavage, once a day) treatment during adolescence [post-natal day (PND) 28-42] on amphetamine (AMPH, 4 mg/kg i.p.)-conditioned place preference (CPP) in early adulthood (PND 60). Our findings showed that AMPH increased CPP for the drug and anxiety-like behaviours; on the other hand, AMPH decreased the number of crossings and recognition index. In addition, AMPH decreased catalase activity and increased reactive species, malondialdehyde and carbonyl protein levels in the hippocampus. AMPH also increased pro-brain derived neurotrophic factor (BDNF), tyrosine kinase receptor B, dopamine transporter, D1R and decreased BDNF and D2R immunoreactivity. Contrarily, animals pre-exposed to MOD showed reduced AMPH-CPP, no locomotor impairment, less anxiety-like behaviours and no memory deficits. In addition, MOD showed antioxidant activity by preventing AMPH-induced oxidative damage in the hippocampus. Moreover, molecular analysis showed that MOD was able to modulate the hippocampal dopaminergic system, thus preventing AMPH-induced impairments. Animals that received MOD during adolescence showed reduced AMPH-CPP in early adulthood. These unexpected behavioural effects of MOD on CPP could be due to its hippocampal dopaminergic system modulation, mainly by its action on D1R, which is closely linked to drug addiction. Nevertheless, further studies are necessary.

Toxicological aspects of interesterified fat: Brain damages in rats.

In recent years, interesterified fat (IF) has been used to replace hydrogenated vegetable fat (HVF), rich in trans isomers, being found in processed foods. Studies involving IF have shown deleterious influences on the metabolic system, similarly to HVF, whereas no studies regarding its influence on the central nervous system (CNS) were performed. Rats from first generation born and maintained under supplementation (3g/Kg, p.o.) of soybean-oil or IF until adulthood were assessed on memory, biochemical and molecular markers in the hippocampus. IF group showed higher saturated fatty acids and linoleic acid and lower docosahexaenoic acid incorporation in the hippocampus. In addition, IF supplementation impaired short and long-term memory, which were related to increased reactive species generation and protein carbonyl levels, decreased catalase activity, BDNF and TrkB levels in the hippocampus. To the best of our knowledge, this is the first study to show that lifelong IF consumption may be related to brain oxidative damage, memory impairments and neurotrophins modifications, which collectively may be present indifferent neurological disorders. In fact, the use of IF in foods was intended to avoid damage from HVF consumption; however this substitute should be urgently reviewed, since this fat can be as harmful as trans fat.

Influence of magnesium supplementation on movement side effects related to typical antipsychotic treatment in rats.

Chronic use of typical antipsychotic haloperidolis related to movement disturbances such as parkinsonism, akathisia and tardive dyskinesia which have been related to excitotoxicity in extrapyramidal brain areas, requiring their prevention and treatment. In the current study we evaluated the influence of the magnesium on prevention (for 28days before-), reversion (for 12days after-) and concomitant supplementation on haloperidol-induced movement disorders in rats. Sub-chronic haloperidol was related to orofacial dyskinesia (OD) and catalepsy development, increased generation of reactive species (RS) and levels of protein carbonyl (PC) in cortex, striatum and substantia nigra (SN) in all experimental protocols. When provided preventatively, Mg reduced the increase of OD and catalepsy time 14 and 7days after haloperidol administration, respectively. When supplemented after haloperidol-induced OD establishment, Mg reversed this behavior after 12days, while catalepsy was reversed after 6days of Mg supplementation.When Mg was concomitantly supplemented with haloperidol administration, OD and catalepsy were prevented. Moreover, Mg supplementation was able to prevent the RS generation in both cortex and SN, reducing PC levels in all brain areas evaluated. When supplemented after haloperidol, Mg reversed RS generation in cortex and striatum, decreasing PC levels in SN and striatum.The co-administration of haloperidol and Mg supplementation prevented RS generation in cortex, striatum and SN, and PC levels in the SN.These outcomes indicate that Mg supplementation may be a useful alternative to prevent movement disturbances resulting of classic antipsychotic pharmacotherapy as haloperidol.

Maternal trans fat intake during pregnancy or lactation impairs memory and alters BDNF and TrkB levels in the hippocampus of adult offspring exposed to chronic mild stress.

This study aimed to assess the influence of maternal dietary fat intake during pregnancy or lactation on memory of adult offspring after chronic mild stress (CMS) exposure. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0g/kg body weight) during pregnancy or lactation. On post-natal day (PND) 60, half of the animals were exposed to CMS following behavioral assessments. While the adult offspring born under influence of SO/FO and HVF supplementations during pregnancy showed higher levels of n-3 and n-6 fatty acids (FA) series DHA and ARA metabolites, respectively, in the hippocampus, adult offspring born from supplemented dams during lactation showed higher levels of their precursors: ALA and LA. However, only HVF supplementation allowed TFA incorporation of adult offspring, and levels were higher in lactation period. Adult offspring born from dams supplemented with trans fat in both pregnancy and lactation showed short and long-term memory impairments before and after CMS. Furthermore, our study also showed higher memory impairment in offspring born from HVF-supplemented dams during lactation in comparison to pregnancy. BDNF expression was increased by stress exposure in offspring from both SO/FO- and HVF-supplemented dams during pregnancy. In addition, offspring from HVF-supplemented dams showed decreased TrkB expression in both supplemented periods, regardless of stress exposure. In conclusion, these findings show for the first time that the type of dietary FA as well as the period of brain development is able to change FA incorporation in brain neural membranes.

Trans fat intake across gestation and lactation increases morphine preference in females but not in male rats: Behavioral and biochemical parameters.

The abuse of morphine has risen considerably in recent years, mainly due to the increase of its prescription in clinical medicine. Also, increased consumption of processed foods, rich in trans fatty acids (TFA), has caused concerns about human health. Thus, the aim of our study was to determine whether trans fat consumption in the perinatal period may affect preference for morphine in adolescent female and male rats. Dams were orally supplemented with water (C-control) or hydrogenated vegetable fat (HVF-rich in TFA) during gestation and lactation periods. On post-natal day 43, pups were exposed to morphine (4mg/kg i.p., for 4 days) and assessed in the conditioned place preference paradigm. Anxiety-like symptoms were assessed, and oxidative status of the brain was estimated by reactive species (RS) generation. Female rats with HVF supplementation showed increased morphine preference and less anxiety-like symptoms. Additionally, both male and female rats from HVF-supplementation showed increased RS generation in the ventral tegmental area, whose level was similar in morphine-conditioned female rats. RS generation was increased in the hippocampus of morphine-conditioned female rats, regardless of the supplementation of their dams. We may infer that gender is a predictive factor to opioid preference, since adolescent female rats showed more susceptibility to addiction than males. Furthermore, trans fat consumption across the perinatal period is able to modify parameters of opioid preference in female rats, possibly due to TFA incorporation in phospholipid membranes, modifying the endogenous opioid system and the oxidative status in brain areas related to drug addiction.

Stress during the gestational period modifies pups' emotionality parameters and favors preference for morphine in adolescent rats.

Experimental animal studies have shown that early life periods are highly vulnerable to environmental factors, which may exert prolonged impact on HPA axis function and on subsequent neurochemical and behavioral responses in adulthood. Here we evaluated the influence of environmental stressful situations in two different early life stages on stress-related behaviors, and morphine-conditioned place preference (CPP), which is indicative of addiction. While in the gestational stress (Gest-S) dams were exposed to daily sessions of chronic mild stress (CMS) for 2 weeks, in the postnatal stress (post-NS) the offspring were exposed daily to neonatal isolation from postnatal day (PND) 2 to PND 9 for 60 min. Animals exposed to post-NS showed lesser anxiety in different behavioral paradigms (elevated plus maze-EPM and defensive burying test-DBT) as well as increased exploratory behavior (open-field task-OFT), and no preference for morphine in CPP. In contrast, animals exposed to Gest-S showed increased corticosterone plasma levels together with anxiety symptoms and greater preference for morphine following three days of drug withdrawal. Our findings indicate that the gestational period is critical for stress, whose effects may be manifest throughout life. On the other hand, post-NS can trigger neuroadaptations able to overcome emotional consequences of early life. We hypothesized that Gest-S is able to modify responses to opioids along adulthood, which may facilitate development of addiction to these drugs.

Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats.

The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.

Olive oil-enriched diet reduces brain oxidative damages and ameliorates neurotrophic factor gene expression in different life stages of rats.

Our aim was to assess the influence of maternal diet rich in monounsaturated fatty acids on oxidative and molecular parameters in brains of mouse pups as well as their body weight during their lifetime. Female rats received a diet containing 20% of olive oil-enriched diet (OOED) and a standard diet control diet (CD) in different periods: pregnancy, lactation and after weaning until pups' adulthood. On the last prenatal day (Group 1), embryos from OOED group showed smaller body weight, brain weight and lower levels of sulphydryl groups glutathione reduced (GSH) in the brain. On postnatal delay-21 (PND21) (Group 2), pups from OOED group showed higher body weight and brain weight, reduced brain weight/body weight ratio and lower brain lipid peroxidation (LP). On PND70 (Group 3), pups from OOED group showed lower brain LP and higher levels of GSH in prefrontal cortex and lower brain levels of reactive species in the hippocampus. Interestingly, the group of animals whose diet was modified from OOED to CD on PND21 showed greater weight gain compared to the group that remained in the same original diet (OOED) until adulthood. Furthermore, OOED consumption during pregnancy and lactation significantly increased BDNF only, as well as its main transcripts exon IV and VI mRNA levels in the prefrontal cortex. In addition, OOED significantly up-regulated FGF-2 mRNA levels in the prefrontal cortex. These findings open a pioneering line of investigation about dietary adjunctive therapeutic strategies and the potential of healthy dietary habits to prevent neonatal conditions and their influence on adulthood.

Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats.

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids--TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine.

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.

Prolonged consumption of trans fat favors the development of orofacial dyskinesia and anxiety-like symptoms in older rats.

Polyunsaturated fatty acids (FAs) are cell membrane components involved in brain functions. We hypothesized that long-term trans fat consumption is able to modify the membrane FAs composition impairing behavioral parameters related to aging. In this study, a comparison of behavioral parameters at 10 and 15 months of trans fat consumption by male Wistar rats was made. Animals were fed for 10 and 15 months from weaning with diets containing either 20% w/w soybean oil (SO), rich in n-6 PUFA, hydrogenated vegetable fat (HVF), rich in trans FAs, or a standard diet (control - C). At both evaluation times, HVF-fed rats showed progressively increased parameters of orofacial dyskinesia, fear and anxiety-like symptoms. The HVF diet reduced locomotor and exploratory activities progressively over 10 and 15 months of supplementation, while the standard and SO diets did not. In this study, we showed that chronic trans FAs consumption from weaning is able to favor the development of neuromotor and neuropsychiatric diseases, whose intensity was time dependent.

Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment.

We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.

Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract.

Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal.