scholarly journals Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1346
Author(s):  
Marco Colizzi ◽  
Riccardo Bortoletto ◽  
Rosalia Costa ◽  
Leonardo Zoccante
Keyword(s):  
Autism Spectrum Disorder ◽  
Animal Studies ◽  
Cannabinoid Receptor ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Glutamate Toxicity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Altered Expression ◽  
Social Exposure

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.

Altered expression of lncRNAs in autism spectrum disorder

2021 ◽  
Author(s):  
Kasra Honarmand Tamizkar ◽  
Soudeh Ghafouri-Fard ◽  
Mir Davood Omrani ◽  
Farkhondeh Pouresmaeili ◽  
Shahram Arsang-Jang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Altered Expression

scholarly journals Vasopressin in the Amelioration of Social Functioning in Autism Spectrum Disorder

2019 ◽  
Vol 8 (7) ◽  
pp. 1061 ◽  
Author(s):  
Mohamed A. Hendaus ◽  
Fatima A. Jomha ◽  
Ahmed H. Alhammadi
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Functioning ◽  
Social Communication ◽  
Animal Studies ◽  
Mammalian Species ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Pharmacological Agents ◽  
Patterns Of Behavior

Autism spectrum disorder (ASD) is a developmental disability described by diagnostic criteria that comprise deficits in social communication and the existence of repetitive, restricted patterns of behavior, interests, or activities that can last throughout life. Many preclinical studies show the importance of arginine vasopressin (AVP) physiology in social functioning in several mammalian species. Currently, there is a trend to investigate more specific pharmacological agents to improve social functioning in patients with ASD. Neurobiological systems that are crucial for social functioning are the most encouraging conceivable signaling pathways for ASD therapeutic discovery. The AVP signaling pathway is one of the most promising. The purpose of this commentary is to detail the evidence on the use of AVP as an agent that can improve social functioning. The pharmacologic aspects of the drug as well as its potential to ameliorate social functioning characteristics in human and animal studies are described in this manuscript. AVP, especially in its inhaled form, seems to be safe and beneficial in improving social functioning including in children with autism. Larger randomized studies are required to implement a long awaited safe and feasible treatment in people with a deficiency in social functioning.

scholarly journals DNA methylation of PGC-1α is associated with elevated mtDNA copy number and altered urinary metabolites in Autism Spectrum Disorder

2021 ◽  
Author(s):  
Sophia Bam ◽  
Erin Buchanan ◽  
Caitlyn Mahony ◽  
Colleen O’Ryan
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Peroxisome Proliferator ◽  
Mtdna Copy Number ◽  
Cpg Sites ◽  
Mtdna Deletions

AbstractBackgroundAutism Spectrum Disorder (ASD) is a complex disorder that is underpinned by numerous dysregulated biological pathways, including canonical mitochondrial pathways. Epigenetic mechanisms contribute to this dysregulation and DNA methylation is an important factor in the aetiology of ASD. We examined the relationship between DNA methylation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), an essential transcriptional regulator of mitochondrial homeostasis, and mitochondrial dysfunction in an ASD cohort of South African children.ResultsUsing targeted Next Generation bisulfite sequencing, we found 12 highly variable CpG sites in PGC-1α that were significantly differentially methylated (p<0.05) between ASD (n = 55) and controls (n = 44). In ASD, eight CpG sites were hypermethylated in the PGC-1α promotor with a putative binding site for CAMP response binding element 1 (CREB1) spanning one of these CpG sites (p = 1 × 10−6). Mitochondrial DNA (mtDNA) copy number, a marker of mitochondrial function, was elevated (p = 0.002) in ASD compared to controls and correlated significantly with DNA methylation at the PGC-1α promoter. There was a positive correlation between methylation at PGC-1α at CpG#1 and mtDNA copy number (Spearman’s r = 0.2, n = 49, p = 0.04) in ASD, but a negative correlation between methylation at PGC-1α at CpG#4 promoter and mtDNA copy number in controls (Spearman’s r = −0.4, n = 42, p = 0.045). While there was no relationship between mtDNA deletions and PGC-1α methylation in ASD, mtDNA deletions correlated negatively with methylation at PGC-1α at CpG#4 (Spearman’s r = −0.4, n = 42, p = 0.032) in controls. Furthermore, levels of urinary organic acids associated with mitochondrial dysfunction correlated significantly (p<0.05) with DNA methylation at PGC-1α CpG#1 and mtDNA copy number in ASD (n= 20) and controls (n= 13) with many of these metabolites involved in altered redox homeostasis and neuroendocrinology.ConclusionsThese data show an association between PGC-1α promoter methylation, elevated mtDNA copy number and metabolomic evidence of mitochondrial dysfunction in ASD. This highlights an unexplored link between DNA methylation and mitochondrial dysfunction in ASD.

Neurobiology of Autism Spectrum Disorder and Intellectual Disability

2017 ◽  
Author(s):  
Jesse Costales ◽  
Silvia De Rubeis ◽  
Jennifer Foss-Feig ◽  
Patrick R. Hof ◽  
Joseph D. Buxbaum ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
Animal Studies ◽  
Adaptive Functioning ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
The Mean ◽  
Emerging Themes ◽  
Integrate Data

Autism spectrum disorder (ASD) is defined by impairments in social communication, along with the presence of restricted and repetitive behaviors. Approximately half of affected children also suffer from intellectual disability (ID), which is defined by cognitive and adaptive functioning at least two standard deviations below the mean (e.g., standard scores <70). It is now well established that genetic factors are major contributors to both ASD and ID. The following chapter will outline emerging themes and integrate data from human and animal studies using genetic, imaging, and histopathological methods. Emerging findings from studies of the immune system and the microbiome will also be briefly reviewed.

scholarly journals Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder

2019 ◽  
Vol 20 (8) ◽  
pp. 1878 ◽  
Author(s):  
Rita Barone ◽  
Renata Rizzo ◽  
Giovanni Tabbì ◽  
Michele Malaguarnera ◽  
Richard E. Frye ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Peroxisome Proliferator Activated Receptors

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.

Altered expression of CCAT1 and CCAT2 lncRNAs in autism spectrum disorder

Gene Reports ◽  
2021 ◽  
pp. 101172
Author(s):  
Mohammad Taheri ◽  
Zahra Younesi ◽  
Sahar Moradi ◽  
Kasra Honarmand Tamizkar ◽  
Katayoon Razjouyan ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Altered Expression

scholarly journals A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Ala Seif ◽  
Carly Shea ◽  
Susanne Schmid ◽  
Ryan A. Stevenson
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Sensory Processing ◽  
Animal Studies ◽  
Neurodevelopmental Disorder ◽  
Sensorimotor Gating ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Functional Implications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review is to compile histological, behavioral, neuroimaging, and electrophysiological evidence from human and animal studies about brainstem contributions and their functional implications in autism. Moreover, due to the developmental nature of autism, the review pays attention to the atypical brainstem development and compares findings based on age. Overall, there is evidence of an important role of brainstem disruptions in ASD, but there is still the need to examine the brainstem across the life span, from infancy to adulthood which could lead the way for early diagnosis and possibly treatment of ASD.

Ketogenic diet as possible therapy of autism spectrum disorder — review and implication

2019 ◽  
Vol 87 (4) ◽  
pp. 218-224
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna
Keyword(s):  
Autism Spectrum Disorder ◽  
Ketogenic Diet ◽  
Animal Studies ◽  
Neurodevelopmental Disorder ◽  
Treatment Strategies ◽  
Medium Chain Triglyceride ◽  
Autism Spectrum ◽  
Human Studies ◽  
Spectrum Disorder ◽  
Therapeutic Effects

Autism spectrum disorder (ASD) has become widespread neurodevelopmental disorder, which currently can be treated with only few therapeutic options. Furthermore, their effectiveness is limited therefore novel treatment strategies for ASD are needed. This review seeks to address this need by discussing a ketogenic diet (KD) in the context of ASD therapy. KD effects have been examined in animal and human studies. They indicate effectiveness of KD by improving autistic features. Moreover, animal studies have revealed clinically useful information about caloric restriction component of KD, which is not necessary to achieve therapeutic effects. Significantly administration of KD but not β-hydroxybutyrate or acetone has a therapeutic effect on social interactions. Human studies are scarce, however previous researches imply KD as an effective treatment at least in certain types of autism. KD in an altered form as: modified Atkins diet (MAD), ketogenic gluten-free diet with supplemental medium-chain triglyceride (MCT), and John Radcliffe ketogenic diet is an alternative to classic KD. These variants provide better quality of nutrition and are less strict, thus less difficult to maintain. KD is described as safe with limited, easily manageable adverse effects. Taken together human and animal studies would seem to suggest that KD will become part of ASD treatment. However, in order to determine accurate recommendations for all ASD patients, further studies are required.

scholarly journals Altered expression of histamine signaling genes in autism spectrum disorder

2017 ◽  
Vol 7 (5) ◽  
pp. e1126-e1126 ◽  
Author(s):  
C Wright ◽  
J H Shin ◽  
A Rajpurohit ◽  
A Deep-Soboslay ◽  
L Collado-Torres ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Altered Expression
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