Research Article
Volume 8 Issue 3 - 2020
Pomegranate and Folate Ameliorate Isolation-Induced Autistic Like Behavior in Experimental Rat Model: Impact on Oxidative, Inflammatory, and Apoptotic Machineries
Azza A Ali1*, Wedad A Hassan2 and Amina K Elansary3
1Professor of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo and Vice Dean of Faculty of Pharmacy, Sinai University, Kantara Branch, Egypt
2Assistant Professor of Physiology, Pharmacology Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt
3Q.C. Specialist, Pharmacology Department, National Organization for Drug Control and Research, Egypt
*Corresponding Author: Azza A Ali, Professor of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo and Vice Dean of Faculty of Pharmacy, Sinai University, Kantara Branch, Egypt.
Received: January 13, 2020; Published: February 14, 2020




Abstract

Recently more infants are prone to early separation from their mothers. Meanwhile, early life experience affects neurodevelopment and stress susceptibility. Maternal separation negatively impacts development causing different psychiatric and neurodevelopmental disorders like autism. In this study, maternal separation was done through separation of pups from their dams for [1.5 hr/day - 11 days]. Seeking protection, pomegranate (500 mg/Kg) and/or folic acid (50 mg/Kg) were ingested by dams during the lactation period (20 days). Maternal separation delayed pups’ eye opening, impaired motor coordination decreased body weight and social activity in an open field arena as well as increased repetitive behavior in neonatal t-maze. Brain monoamine and reduced glutathione were decreased while nitric oxide, interleukin-1beta and caspase-3 were increased. Meanwhile intake of pomegranate and/or folic acid reversed maternal separation induced behavioral and biochemical changes. The combination protected against development of autistic-like symptoms in rats through modification of cells redox state and inflammation.

Keywords: Autism; Maternal Separation; Pomegranate; Folic Acid; Apoptosis

References

  1. Ebihara K., et al. "Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD". Behavioural Brain Research 334 (2017): 6-15.
  2. Fombonne E. "Epidemiology of Pervasive Developmental Disorders". Pediatric Research 65.6 (2009): 591-598.
  3. Coffman MC., et al. "Sex differences in social perception in children with ASD". Journal of Autism and Developmental Disorders 45.2 (2015): 589-599.
  4. Kikusui T., et al. "Maternal deprivation by early weaning increases corticosterone and decreases hippocampal BDNF and neurogenesis in mice". Psychoneuroendocrinology 34.5 (2009): 762-772.
  5. Lehmann J and J Feldon. "Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing?". Reviews in the Neurosciences 11.4 (2000): 383-408.
  6. Chauhan A., et al. “Autism: oxidative stress, inflammation, and immune abnormalities” (2009).
  7. McDougle CJ., et al. "Toward an immune-mediated subtype of autism spectrum disorder". Brain Research 1617 (2015): 72-92.
  8. Heber D., et al. "Safety and antioxidant activity of a pomegranate ellagitannin-enriched polyphenol dietary supplement in overweight individuals with increased waist size". Journal of Agricultural and Food Chemistry 55.24 (2007): 10050-10054.
  9. Ahmed MA., et al. "Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats". Life Sciences 110.2 (2014): 61-69.
  10. Ornoy A., et al. "Prenatal factors associated with autism spectrum disorder (ASD)". Reproductive Toxicology 56 (2015): 155-169.
  11. Perry SW., et al. "Antioxidants are required during the early critical period, but not later, for neuronal survival". Journal of Neuroscience Research 78.4 (2004): 485-192.
  12. Ullegaddi R., et al. "B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke". Clinical Science 107.5 (2004): 477-484.
  13. Desai A., et al. "The metabolic basis for developmental disorders due to defective folate transport". Biochimie 126 (2016): 31-42.
  14. Bahi A. "Sustained lentiviral-mediated overexpression of microRNA124a in the dentate gyrus exacerbates anxiety- and autism-like behaviors associated with neonatal isolation in rats". Behavioural Brain Research 311 (2016): 298-308.
  15. Schneider T and R Przewlocki. "Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism". Neuropsychopharmacology 30.1 (2005): 80-89.
  16. Thomas J., et al. "Augmentation of effect of venlafaxine by folic acid in behavioral paradigms of depression in mice: Evidence of serotonergic and pro-inflammatory cytokine pathways". Pharmacological Reports 68.2 (2016): 396-403.
  17. Zbinden G. "Experimental methods in behavioral teratology". Archives of Toxicology 48.2-3 (1981): 69-88.
  18. Vorhees CV. "Fetal anticonvulsant syndrome in rats: dose- and period-response relationships of prenatal diphenylhydantoin, trimethadione and phenobarbital exposure on the structural and functional development of the offspring". Journal of Pharmacology and Experimental Therapeutics 227.2 (1983): 274-287.
  19. Ramirez RL and LP Spear. "Ontogeny of ethanol-induced motor impairment following acute ethanol: assessment via the negative geotaxis reflex in adolescent and adult rats". Pharmacology Biochemistry and Behavior 95.2 (2010): 242-248.
  20. Chang YC., et al. "Behavioral Phenotyping for Autism Spectrum Disorders in Mice". Current Protocols in Toxicology 72 (2017): 1-21.
  21. Calzavara MB., et al. "Effects of antipsychotics and amphetamine on social behaviors in spontaneously hypertensive rats". Behavioural Brain Research 225.1 (2011): 15-22.
  22. Cunha JM and J Masur. "Evaluation of psychotropic drugs with a modified open field test". Pharmacology 16.5 (1978): 259-267.
  23. Vorhees CV. "Some behavioral effects of maternal hypervitaminosis A in rats". Teratology 10.3 (1974): 269-273.
  24. Ciarlone AE. "Further modification of a fluorometric method for analyzing brain amines". Microchemical Journal 23.1 (1978): 9-12.
  25. Montgomery HAC and JF Dymock. "The determination of nitrite in water". Analyst 86 (1961): 414-416.
  26. Beutler E., et al. "Improved method for the determination of blood glutathione". Journal of Laboratory and Clinical Medicine 61 (1963): 882-888.
  27. Sandhya T., et al. "Bacopa monniera (L.) Wettst ameliorates behavioral alterations and oxidative markers in sodium valproate induced autism in rats". Neurochemical Research 37.5 (2012): 1121-1131.
  28. P A., et al. "Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome". Brain, Behavior, and Immunity 25 (2011): 40-45.
  29. Sheikh AM., et al. "BDNF-Akt-Bcl2 antiapoptotic signaling pathway is compromised in the brain of autistic subjects". Journal of Neuroscience Research 88.12 (2010): 2641-2647.
  30. Shetty RA and M Sadananda. "Brief Social Isolation in the Adolescent Wistar-Kyoto Rat Model of Endogenous Depression Alters Corticosterone and Regional Monoamine Concentrations". Neurochemical Research 42.5 (2017): 1470-1477.
  31. Guo YP and KG Commons. "Serotonin neuron abnormalities in the BTBR mouse model of autism". Autism Research 10.1 (2017): 66-77.
  32. Mosienko V., et al. "Life without brain serotonin: reevaluation of serotonin function with mice deficient in brain serotonin synthesis". Behavioural Brain Research 277 (2015): 78-88.
  33. Bahmani Z., et al. "Prefrontal Contributions to Attention and Working Memory". Current Topics in Behavioral Neurosciences (2019).
  34. Kim H., et al. "Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder". Behavioral and Brain Functions 12.1 (2016): 3.
  35. Sara SJ and S Bouret "Orienting and reorienting: the locus coeruleus mediates cognition through arousal". Neuron 76.1 (2012): 130-141.
  36. Du J., et al. "The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors". Critical Reviews in Food Science and Nutrition 56.15 (2016): 2560-2578.
  37. Tee AR., et al. "The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex". Seminars in Cell and Developmental Biology 52 (2016): 12-20.
  38. Franco R and JA Cidlowski. "Apoptosis and glutathione: beyond an antioxidant". Cell Death & Differentiation 16.10 (2009): 1303-1314.
  39. Hegazy HG., et al. "Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model". Cytokine 71.2 (2015): 173-180.
  40. Yirmiya R and I Goshen. "Immune modulation of learning, memory, neural plasticity and neurogenesis". Brain, Behavior, and Immunity 25.2 (2011): 181-213.
  41. Deep SN., et al. "Neuroprotective Role of L-NG-Nitroarginine Methyl Ester (L-NAME) against Chronic Hypobaric Hypoxia with Crowding Stress (CHC) Induced Depression-Like Behaviour". PLoS One 11.4 (2016): e0153371.
  42. Loren DJ., et al. "Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury". Pediatric Research 57.6 (2005): 858-864.
  43. Naveen S., et al. "Anti-depressive effect of polyphenols and omega-3 fatty acid from pomegranate peel and flax seed in mice exposed to chronic mild stress". Psychiatry and Clinical Neurosciences 67.7 (2013): 501-508.
  44. Braidy N., et al. "Neuroprotective effects of a variety of pomegranate juice extracts against MPTP-induced cytotoxicity and oxidative stress in human primary neurons". Oxidative Medicine and Cellular Longevity (2013): 685909.
  45. Al-Farsi YM., et al. "Low folate and vitamin B12 nourishment is common in Omani children with newly diagnosed autism". Nutrition 29.3 (2013): 537-541.
  46. Jin C., et al. "Methyl donors dietary supplementation to gestating sows diet improves the growth rate of offspring and is associating with changes in expression and DNA methylation of insulin-like growth factor-1 gene". Journal of Animal Physiology and Animal Nutrition 102.5 (2018): 1340-1350.
  47. Canever L., et al. "Changes in behavioural parameters, oxidative stress and neurotrophins in the brain of adult offspring induced to an animal model of schizophrenia: The effects of FA deficient or FA supplemented diet during the neurodevelopmental phase". Progress in Neuro-Psychopharmacology and Biological Psychiatry 86 (2018): 52-64.
  48. McCarty MF., et al. "High-dose folate and dietary purines promote scavenging of peroxynitrite-derived radicals--clinical potential in inflammatory disorders". Medical Hypotheses 73.5 (2009): 824-834.
  49. Miller MW. “Brain development: normal processes and the effects of alcohol and nicotine”. Brain Development (2006).
  50. Yu HL., et al. "Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35". British Journal of Nutrition 102.5 (2009): 655-662.
Citation: Azza A Ali., et al. “Pomegranate and Folate Ameliorate Isolation-Induced Autistic Like Behavior in Experimental Rat Model: Impact on Oxidative, Inflammatory, and Apoptotic Machineries”. EC Pharmacology and Toxicology 8.3 (2020): 01-13.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


August Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the August issue of respective journals and can be viewed in the current issue pages.

Submission Deadline for September Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the September issue of respective journals. Submissions are accepted on/before August 26, 2020.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to editor@ecronicon.uk