Effects ofω-3 Polyunsaturated Fatty Acids on Plasma Proteome in Rett Syndrome

The mechanism of action of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) is only partially known. Prior reports suggest a partial rescue of clinical symptoms and oxidative stress (OS) alterations followingω-3 PUFAs supplementation in patients with Rett syndrome (RTT), a devastating neurodevelopmental disorder with transient autistic features, affecting almost exclusively females and mainly caused by sporadic mutations in the gene encoding the methyl CpG binding protein 2 (MeCP2) protein. Here, we tested the hypothesis thatω-3 PUFAs may modify the plasma proteome profile in typical RTT patients withMECP2mutations and classic phenotype. A total of 24 RTT girls at different clinical stages were supplemented withω-3 PUFAs as fish oil for 12 months and compared to matched healthy controls. The expression of 16 proteins, mainly related to acute phase response (APR), was changed at the baseline in the untreated patients. Followingω-3 PUFAs supplementation, the detected APR was partially rescued, with the expression of 10 out of 16 (62%) proteins being normalized.ω-3 PUFAs have a major impact on the modulation of the APR in RTT, thus providing new insights into the role of inflammation in autistic disorders and paving the way for novel therapeutic strategies.

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Whole brain delivery of an instability-prone Mecp2 transgene improves behavioral and molecular pathological defects in mouse models of Rett syndrome

eLife ◽

10.7554/elife.52629 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Mirko Luoni ◽

Serena Giannelli ◽

Marzia Tina Indrigo ◽

Antonio Niro ◽

Luca Massimino ◽

...

Keyword(s):

Rett Syndrome ◽

Neurodevelopmental Disorder ◽

Protein Translation ◽

Mutant Mice ◽

Gene Encoding ◽

Strong Immune Response ◽

Intravenous Injections ◽

Protein Levels ◽

Mecp2 Protein ◽

The Brain

Rett syndrome is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy for this disease presents inherent hurdles since MECP2 is expressed throughout the brain and its duplication leads to severe neurological conditions as well. Herein, we use the AAV-PHP.eB to deliver an instability-prone Mecp2 (iMecp2) transgene cassette which, increasing RNA destabilization and inefficient protein translation of the viral Mecp2 transgene, limits supraphysiological Mecp2 protein levels. Intravenous injections of the PHP.eB-iMecp2 virus in symptomatic Mecp2 mutant mice significantly improved locomotor activity, lifespan and gene expression normalization. Remarkably, PHP.eB-iMecp2 administration was well tolerated in female Mecp2 mutant or in wild-type animals. In contrast, we observed a strong immune response to the transgene in treated male Mecp2 mutant mice that was overcome by immunosuppression. Overall, PHP.eB-mediated delivery of iMecp2 provided widespread and efficient gene transfer maintaining physiological Mecp2 protein levels in the brain.

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Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review

Medicina ◽

10.3390/medicina57090893 ◽

2021 ◽

Vol 57 (9) ◽

pp. 893

Author(s):

Aleksandra Veselinović ◽

Snježana Petrović ◽

Vladica Žikić ◽

Miško Subotić ◽

Vladimir Jakovljević ◽

...

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Added Value ◽

Omega 3 ◽

Behavioral Deficits ◽

Pufa Supplementation ◽

Children With Asd ◽

Patterns Of Behavior

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child’s brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut–brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits.

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A Plasma Proteomic Approach in Rett Syndrome: Classical versus Preserved Speech Variant

Mediators of Inflammation ◽

10.1155/2013/438653 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Alessio Cortelazzo ◽

Roberto Guerranti ◽

Claudio De Felice ◽

Cinzia Signorini ◽

Silvia Leoncini ◽

...

Keyword(s):

Rett Syndrome ◽

Neurodevelopmental Disorder ◽

Phenotypic Expression ◽

Complement C3 ◽

Plasma Proteome ◽

Gene Encoding ◽

Expression Variability ◽

Proteomic Approach ◽

Clinical Presentations ◽

Alpha 1 Antitrypsin

Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Although over 200 mutations types have been identified so far, nine of which the most frequent ones. A wide phenotypical heterogeneity is a well-known feature of the disease, with different clinical presentations, including the classical form and the preserved speech variant (PSV). Aim of the study was to unveil possible relationships between plasma proteome and phenotypic expression in two cases of familial RTT represented by two pairs of sisters, harbor the sameMECP2gene mutation while being dramatically discrepant in phenotype, that is, classical RTT versus PSV. Plasma proteome was analysed by 2-DE/MALDI-TOF MS. A significant overexpression of six proteins in the classical sisters was detected as compared to the PSV siblings. A total of five out of six (i.e., 83.3%) of the overexpressed proteins were well-known acute phase response (APR) proteins, including alpha-1-microglobulin, haptoglobin, fibrinogen beta chain, alpha-1-antitrypsin, and complement C3. Therefore, the examined RTT siblings pairs proved to be an important benchmark model to test the molecular basis of phenotypical expression variability and to identify potential therapeutic targets of the disease.

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Effects of Omega-3 Polyunsaturated Fatty Acids to The Serum Level of Interleukin-8, Percentage of Forced Expiratory Volume in 1 Second (%FEV1), and COPD Assesment Test Scores in Stable COPD Patients

Jurnal Respirologi Indonesia ◽

10.36497/jri.v37i4.80 ◽

2017 ◽

Vol 37 (4) ◽

pp. 265-277

Author(s):

Nisfi Angriani ◽

Suradi Suradi ◽

Yusup Subagio

Keyword(s):

Fatty Acids ◽

Treatment Group ◽

Polyunsaturated Fatty Acids ◽

Clinical Symptoms ◽

Smoke Inhalation ◽

Control Group ◽

Omega 3 ◽

Copd Patients ◽

Significant Difference ◽

And Control

Backgorund: Cigarette smoke inhalation and the other exposure can cause of airway inflammatory and it was the most cause of chronic obstruction pulmonary desease (COPD) pathogenesis. The airway inflammatory will release cytokines proinflammation, one of them was interleukin (IL)-8. Omega-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effect and its can decrease cytokines production in COPD pathogenesis. Methods: This study aimed to analyze effects of omega 3 PUFAs on serum IL-8, %FEV1, and CAT score in stable COPD patients. Clinical trials of experimental with pretest and posttest designs were conducted of 32 stable COPD patients came to clinic in Dr. Moewardi Hospital Surakarta from December 2016 until February 2017. Samples were taken by consecutive sampling. Subjects were divided into two groups include the treatment group (n=16) received standard COPD therapy omega 3 PUFA 600mg/day and the control group (n=16) received only standard COPD therapy for 28 days. Results: There were significant difference (P=0.0001) towards decreased of serum IL-8 between treatment group (-3.56+5.32pg/ml) and control group (8.90+9.98pg/ml), increase difference were no significantly of %VEP1 value (P=0.473) between treatment group (7.02+7.17pg/ml) and control group (5.32+5.97pg/ml), decrease difference of CAT scores significantly (P=0.0001) between treatment group (-16.13+3.03pg/ml) and control group (-4.75+4.17pg/ml). Conclusions: Omega-3 PUFA may decrease airway inflammation with decrease serum IL-8 level significantly, increase of %FEV1 no significantly and improve the clinical symptoms of stable COPD by decreased CAT scores significantly in stable COPD patients. (J Respir Indo. 2017; 37(4): 265-77)

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Omega‐3 polyunsaturated fatty acids supplementation improve clinical symptoms in patients with Covid‐19: A randomised clinical trial

International Journal of Clinical Practice ◽

10.1111/ijcp.14854 ◽

2021 ◽

Author(s):

Mohsen Sedighiyan ◽

Hamed Abdollahi ◽

Elmira Karimi ◽

Mostafa Badeli ◽

Reza Erfanian ◽

...

Keyword(s):

Clinical Trial ◽

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Clinical Symptoms ◽

Randomised Clinical Trial ◽

Omega 3

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A randomized, double-blind, placebo-controlled study of polyunsaturated fatty acids efficacy in adolescents with anorexia nervosa

Pharmacotherapy in Psychiatry and Neurology ◽

10.33450/fpn.2020.06.001 ◽

2020 ◽

Vol 36 (2) ◽

pp. 95-106

Author(s):

Agnieszka M. Piróg-Balcerzak ◽

Anna K. Bażyńska ◽

Katarzyna Biernacka ◽

Joanna Brągoszewska ◽

Lidia Popek ◽

...

Keyword(s):

Fatty Acids ◽

Anorexia Nervosa ◽

Polyunsaturated Fatty Acids ◽

Small Sample Size ◽

Small Sample ◽

Female Adolescent ◽

Eating Attitude ◽

Controlled Study ◽

Omega 3 ◽

Eat 26

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.

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