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1.
Crit Rev Food Sci Nutr ; 56(12): 2021-35, 2016 Sep 09.
Article in English | MEDLINE | ID: mdl-26068122

ABSTRACT

The two basic questions in food intake study are what we eat, and how much do we eat. Most research is directed toward the control of how much is eaten. This is likely the result of the increased number of individuals with eating disorders in the Western world. Feeding behavior is highly complex, and is controlled by many psychological, physiological, biochemical, and immunological factors. The aim of this review is to clarify the involvement of fatty acids in eating disorders such as anorexia and binge eating disorder. The review will describe the modified fatty acid profile observed in individuals with anorexia or binge eating disorder, and discuss on what factors fatty acids can exert beneficial effects. In addition, the differences and similarities between anorexia and binge eating disorder will be discussed. We suggest that beneficial effects of essential fatty acids on both anorexia and binge eating disorder can be explained by the stabilizing effect of those fatty acids on the neuronal membrane fluidity index.


Subject(s)
Anorexia Nervosa , Fatty Acids, Essential/physiology , Obesity , Animals , Anorexia Nervosa/physiopathology , Binge-Eating Disorder/physiopathology , Blood-Brain Barrier , Brain , Diet , Feeding Behavior , Feeding and Eating Disorders/physiopathology , Humans , Membrane Fluidity , Myelin Sheath , Neurons/physiology , Neurotransmitter Agents , Obesity/physiopathology
2.
J Neural Transm (Vienna) ; 122(5): 629-41, 2015 May.
Article in English | MEDLINE | ID: mdl-25292362

ABSTRACT

Our previous study demonstrated that an olfactory bulbectomy in rats induced short-term, multifaceted, devastating Alzheimer's-like effects, which included cognitive impairment, hyperactivity, hyperthermia, and increased levels of homocysteine and pro-inflammatory cytokines, including IL-17A. In addition, the rats exhibited an increase in the hyperphosphorylation of brain Tau proteins and in the number of neurofibrillary tangles. Here, we examined the long-term effects of the surgery and found that olfactory bulbectomy also rendered the rats to become anemic with brain iron overload. Additionally, a significant reduction in the membrane fluidity index in frontal cortex synaptosomes was found. Treatment with a mixture of n - 3/n - 6 of fatty acids restored the unwanted effect. The beneficial effects of fatty acids are mediated via the effects of fatty acids on the neuronal membrane structure and fluidity. These findings are similar to Alzheimer's symptoms, which suggest this model can be used as an animal model for Alzheimer's disease. We recommend using this model to scan potential new anti-Alzheimer's drugs.


Subject(s)
Brain/drug effects , Fatty Acids/administration & dosage , Neurodegenerative Diseases/drug therapy , Neurons/drug effects , Neuroprotective Agents/administration & dosage , Olfactory Bulb/physiopathology , Alzheimer Disease , Animals , Avoidance Learning/drug effects , Avoidance Learning/physiology , Body Temperature Regulation/drug effects , Body Temperature Regulation/physiology , Brain/metabolism , Cholesterol/metabolism , Cytokines/blood , Disease Models, Animal , Eating/drug effects , Eating/physiology , Homocysteine/metabolism , Iron/metabolism , Male , Maze Learning/drug effects , Maze Learning/physiology , Motor Activity/drug effects , Motor Activity/physiology , Neurodegenerative Diseases/physiopathology , Neurodegenerative Diseases/psychology , Neurons/metabolism , Rats, Long-Evans , Synaptosomes/drug effects , Synaptosomes/metabolism
3.
Brain Pathol ; 22(3): 280-94, 2012 May.
Article in English | MEDLINE | ID: mdl-21929559

ABSTRACT

α-Synuclein (α-Syn) is a neuronal protein that accumulates progressively in Parkinson's disease (PD) and related synucleinopathies. Attempting to identify cellular factors that affect α-Syn neuropathology, we previously reported that polyunsaturated fatty acids (PUFAs) promote α-Syn oligomerization and aggregation in cultured cells. We now report that docosahexaenoic acid (DHA), a 22:6 PUFA, affects α-Syn oligomerization by activating retinoic X receptor (RXR) and peroxisome proliferator-activated receptor γ2 (PPARγ2). In addition, we show that dietary changes in brain DHA levels affect α-Syn cytopathology in mice transgenic for the PD-causing A53T mutation in human α-Syn. A diet enriched in DHA, an activating ligand of RXR, increased the accumulation of soluble and insoluble neuronal α-Syn, neuritic injury and astrocytosis. Conversely, abnormal accumulations of α-Syn and its deleterious effects were significantly attenuated by low dietary DHA levels. Our results suggest a role for activated RXR/PPARγ 2, obtained by elevated brain PUFA levels, in α-Syn neuropathology.


Subject(s)
Brain/metabolism , Docosahexaenoic Acids/metabolism , Parkinson Disease/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , alpha-Synuclein/metabolism , Animals , Brain/pathology , Disease Models, Animal , Mice , Mice, Transgenic , Neurons/metabolism , Neurons/pathology , Parkinson Disease/genetics , Parkinson Disease/pathology , Receptors, Cytoplasmic and Nuclear/genetics , alpha-Synuclein/genetics
4.
J Interferon Cytokine Res ; 29(7): 393-8, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19450150

ABSTRACT

Sleep deprivation is a major health problem in modern society. Deprivation of rapid eye movement (REM) sleep is particularly damaging to cognition and to spatial memory; however, the mechanisms that mediate these deteriorations in function are not known. We explored the possibility that REM sleep deprivation may provoke major changes in the immune system by inducing inflammation. Rats were subjected to 72 h of REM sleep deprivation, and the plasma levels of proinflammatory cytokines (IL-1, IL-1beta, IL-6, IL-17A, and TNF-alpha), an anti-inflammatory cytokine (IL-10), the inflammatory markers homocysteine, corticosterone, and hyperthermia were measured immediately after the deprivation period, and 7 days later. The results indicate that REM sleep deprivation induced an inflammatory response. The levels of the proinflammatory cytokines and markers were significantly elevated in sleep-deprived rats as compared to control rats. After 7 days of recovery, the levels of some markers, including hyperthermia, remained higher in sleep-deprived rats versus the control animals. IL-17A appears to play a pivotal role in coordinating the inflammation. These data shed new light on the mechanism of sleep deprivation-induced inflammation.


Subject(s)
Inflammation , Interleukin-17/blood , Sleep Deprivation/immunology , Animals , Biomarkers/blood , Corticosterone/blood , Fever , Homocysteine/blood , Interleukin-17/classification , Male , Rats , Rats, Long-Evans , Up-Regulation
5.
J Child Adolesc Psychopharmacol ; 19(2): 167-77, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19364294

ABSTRACT

Essential fatty acids (EFA) are needed for normal sensory, cognitive, and motor function. The EFA blood profile seems to be different in children with attention-deficit/hyperactivity disorder (ADHD) as compared to matched controls. Previous open EFA supplementation trials were successful in demonstrating significant therapeutic effects in this population, whereas most of the randomized controlled trials failed to show any benefit over placebo. The current randomized, double-blind, placebo-controlled trial tested the influence of short-chain EFA supplementation on ADHD children, using parent and teacher questionnaires and a computerized continuous performance test. A total of 73 unmedicated children aged 7-13 years with a diagnosis of ADHD participated in the study; 63 children completed the study. The EFA supplement contained 480 mg of linoleic acid and 120 mg of alpha-linolenic acid, and the placebo contained 1000 mg of vitamin C (daily amounts); both were given for a 7-week supplementation period. Analysis of variance for repeated measures revealed that both treatments ameliorated some of the symptoms, but no significant differences were found between the groups in any of the treatment effects.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Fatty Acids, Essential/adverse effects , Fatty Acids, Essential/therapeutic use , Psychological Tests , Adolescent , Child , Dose-Response Relationship, Drug , Double-Blind Method , Drug Combinations , Fatty Acids, Essential/administration & dosage , Female , Humans , Linoleic Acid/administration & dosage , Linoleic Acid/adverse effects , Linoleic Acid/therapeutic use , Male , Psychomotor Performance/drug effects , Surveys and Questionnaires , alpha-Linolenic Acid/administration & dosage , alpha-Linolenic Acid/adverse effects , alpha-Linolenic Acid/therapeutic use
6.
Nutr Neurosci ; 11(4): 167-71, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18681985

ABSTRACT

Despite some successful interventions and the large research efforts on this topic, iron deficiency and anemia remain the most common nutritional disorders in the world today. Recently, several researchers indicated that early, induced, iron deficiency produced a long-lasting effect even if the hemoglobin and iron levels returned to normal values. Recent human studies showed that 10-12-year-old children, who were iron deficient at age 1 year, showed lower IQ scores. In this study, we tried to imitate this condition by inducing iron deficiency in rats at age 21 days, for 28 days, and then tested the rats on day 120. The former iron-deficient rats had normal hematological and motor activity values, and normal thermoregulatory response, but they were very slow learners compared to the control rats. Treatment with a mixture of essential fatty acids improved their learning capacity.


Subject(s)
Anemia, Iron-Deficiency/complications , Cognition , Fatty Acids, Essential/therapeutic use , Anemia, Iron-Deficiency/drug therapy , Anemia, Iron-Deficiency/physiopathology , Animals , Hemoglobins/analysis , Iron/blood , Iron, Dietary/administration & dosage , Learning Disabilities/drug therapy , Learning Disabilities/etiology , Male , Maze Learning , Motor Activity , Rats , Rats, Long-Evans
7.
Nutr Neurosci ; 10(5-6): 269-71, 2007.
Article in English | MEDLINE | ID: mdl-18284035

ABSTRACT

Rapid eye movements (REM) deprivation induces complex deteriorating effects, which include brain morphological changes such as reduced neurogenesis processes, brain neurochemical and hormonal modifications, and cognitive decline. One of the major effects of REM deprivation is an increased anxiety level. The aim of this study was to examine the effects ofpretreatment with a specific mixture of essential fatty acids on the increased level of anxiety on the behavioral level (elevated plus maze), on the hormonal level (corticosterone level) and on the physiological level (thermoregulation). The results showed that pretreatment with a mixture of essential fatty acids protect the rats from the anxiolytic effects of REM deprivation. The effects of essential fatty acids on sleep mechanisms, on the one hand, and on anxiety levels, on the other hand, may explain the beneficial effects of the pretreatment.


Subject(s)
Anxiety/etiology , Anxiety/prevention & control , Fatty Acids, Essential/administration & dosage , Sleep Deprivation/complications , Animals , Body Temperature Regulation/drug effects , Body Temperature Regulation/physiology , Corticosterone/blood , Male , Rats , Rats, Sprague-Dawley
8.
Nutr Neurosci ; 8(4): 265-7, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16491653

ABSTRACT

Test anxiety is an incapacitating academic syndrome. This study shows that administration of a polyunsaturated fatty acid mixture of omega-3 and -6 can improve the behavioral variables associated with this type of anxiety, i.e. appetite, mood, mental concentration, fatigue, academic organization and poor sleep, as well as lowering elevated cortisol level, with a corresponding reduction of anxiety.


Subject(s)
Anxiety/prevention & control , Educational Measurement , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-6/administration & dosage , Affect , Appetite , Humans , Hydrocortisone/blood , Linoleic Acid/administration & dosage , Male , Placebos , Test Anxiety Scale , alpha-Linolenic Acid/administration & dosage
9.
J Perinatol ; 24(12): 757-62, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15318248

ABSTRACT

OBJECTIVE: This study was conducted to examine the relation between iron status and neurobehavioral development in premature infants. STUDY DESIGN: Infants born before 34 weeks postmenstrual age and who were medically stable were studied. Anemia was defined as hemoglobin < or =10 g/Dl and low iron stores as a serum ferritin concentration < or =75 microg/l. The infants were classified as anemic with low ferritin (Group 1; n=18), anemic with normal ferritin (Group 2; n=14), and nonanemic with normal ferritin (Group 3; n=21). A total of 18 reflexes were behaviorally evaluated at 37 weeks postmenstrual age and "reflex scores" were compared between the groups. Higher scores reflect a greater percentage of abnormal reflexes. RESULTS: Infants in group 1 (anemia/low ferritin) had a significantly higher reflex score (51.45+/-18.32%) than infants in Group 3 (38.32+/-17.75%). Group 2 had an intermediate score (45.40+/-21.70%), but not different from the other two groups. CONCLUSION: These data indicate that low iron status, both measured by anemia and ferritin levels, is related to poorer neurobehavioral status in premature infants.


Subject(s)
Child Development/physiology , Hemoglobins/metabolism , Infant Behavior/physiology , Infant, Premature/physiology , Infant, Premature/psychology , Reflex/physiology , Birth Weight , Female , Ferritins/blood , Gestational Age , Humans , Infant, Newborn , Male
10.
Nutr Neurosci ; 7(2): 85-90, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15279494

ABSTRACT

Iron deficiency (ID) is among the most common nutritional diseases, causing deleterious effects that include decreases in cognitive function and weight loss. The ID also induces a reduction in the number and affinity of dopaminergic D2 receptors. The new finding that ID induces an increase in the pancreas cells, leads to the hypothesis that cholecystokinin-8 (CCK-8) is involved in the ID effects. The level of CCK-8 was higher among ID rats, compared with normal rats. The ID rats in our study were anorectic and performed poorly in learning tests (Morris water maze and passive avoidance learning). Essential fatty acids (EFA) mediate dopamine activity and have been found to rehabilitate learning deficits. Treatment with a fatty acid compound blocked both the learning deficits and the anorexia, while a CCK-8 antagonist was successful only against the anorectic effects.


Subject(s)
Avoidance Learning/physiology , Cholecystokinin/antagonists & inhibitors , Iron Deficiencies , Linoleic Acid/pharmacology , Peptide Fragments/antagonists & inhibitors , Proglumide/analogs & derivatives , Proglumide/pharmacology , Animal Feed , Animals , Avoidance Learning/drug effects , Cholecystokinin/blood , Energy Intake , Hormone Antagonists/pharmacology , Islets of Langerhans/anatomy & histology , Islets of Langerhans/drug effects , Male , Motor Activity/drug effects , Peptide Fragments/blood , Rats , Rats, Long-Evans , Swimming , Weight Gain
11.
Psychoneuroendocrinology ; 29(2): 113-24, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14604595

ABSTRACT

The role of fatty acids (FA) and their impact on nervous system activity and immune function has attracted much attention. The interest extends beyond a basic understanding of the potential role exerted by FA on the neuronal membrane and its properties, to the implications and clinical significance for many neurological disorders. This is especially true for epilepsy, where many conventional anticonvulsant preparations carry undesired side effects, and a significant number of patients remain refractory to the drug treatment. We report on a comparative examination in rats of carbamazepine (CBZ) and SR-3 (a fatty acid compound) with respect to seizure control efficiency, as well as protective features against cognitive impairment and cortisol level elevation. With pentylenetetrazol (PTZ) induced seizures pre-treated by CBZ, or SR-3, both CBZ and SR-3 were equally effective in providing seizure control and both were superior to the saline control. However SR-3 provided greater protection in Morris Water Maze performance and control of cortisol level elevation.


Subject(s)
Anticonvulsants/pharmacology , Carbamazepine/pharmacology , Epilepsy/drug therapy , Hydrocortisone/blood , Linolenic Acids/pharmacology , Analysis of Variance , Animals , Disease Models, Animal , Epilepsy/blood , Escape Reaction/drug effects , Male , Maze Learning/drug effects , Neuroprotective Agents/pharmacology , Pentylenetetrazole , Rats , Rats, Long-Evans , Seizures/chemically induced , Seizures/prevention & control , alpha-Linolenic Acid/pharmacology
13.
Neurobiol Aging ; 23(5): 843-53, 2002.
Article in English | MEDLINE | ID: mdl-12392789

ABSTRACT

In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects.


Subject(s)
Aging/metabolism , Fatty Acids, Unsaturated/metabolism , Neurons/metabolism , Aged , Cell Membrane/metabolism , Humans
14.
Pharmacol Biochem Behav ; 72(1-2): 7-11, 2002 May.
Article in English | MEDLINE | ID: mdl-11900763

ABSTRACT

Tyrosine is unable to cross the blood-brain barrier and is therefore unable to improve the status of brain dopamine (DA) and to provide relief for patients with Parkinson's disease (PD) or other DA-insufficient disorders. We report the creation of an amide bond molecule [N-(alpha-linolenoyl)tyrosine (NLT)] that combines tyrosine with a fatty acid mixture. NLT significantly improves the rotational behavior of rats [following unilateral striatal lesions (as a model for Parkinson's)] and overcomes the exaggerated eye-blinking induced by a potent DA-depleting agent (as a model for essential blepharospasm). These results are supported by the finding that NLT's mode of action, in striatum, is the same as the mode of action of D-amphetamine. They both induce an increase in the DA level, DA turnover and release.


Subject(s)
Antiparkinson Agents/pharmacology , Linolenic Acids/chemical synthesis , Linolenic Acids/pharmacology , Linolenic Acids/therapeutic use , Tyrosine/chemical synthesis , Tyrosine/pharmacology , Tyrosine/therapeutic use , alpha-Linolenic Acid/pharmacology , Animals , Antiparkinson Agents/chemical synthesis , Antiparkinson Agents/therapeutic use , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine/metabolism , Drug Evaluation, Preclinical/methods , Male , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/metabolism , Rats , Rats, Sprague-Dawley , Tyrosine/analogs & derivatives , alpha-Linolenic Acid/chemical synthesis , alpha-Linolenic Acid/therapeutic use
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