The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients

Siniscalco, Dario; Sapone, Anna; Giordano, C; Cirillo, Alessandra; Novellis, Vito de; Magistris, Laura de; Rossi, Francesco; Fasano, Alessio; Maione, Sabatino; Antonucci, Nicola

doi:10.1007/s10803-011-1373-z

Cited by 64 publications

(47 citation statements)

References 56 publications

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“…Indeed, accumulating evidence suggests that dysregulated apoptotic processes might play a crucial role in the ASD pathogenesis [60]. In ASD, decreased levels of the antiapoptotic signalling pathway in brain have been described and enhanced expression of several caspases in peripheral blood mononuclear cells have been reported [61][62][63]. Considering this fact, it is tempting to speculate that altered homeostasis between neurotrophins and their receptors would cause pathological activation of apoptotic death pathways that lead to alterations of the precise neurodevelopmental process and possibly to developmental disabilities found in ASD pathology [60].…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

et al. 2014

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Autism spectrum disorders (ASD) comprise neurodevelopmental disorders with clinical onset during the first years of life. The identification of peripheral biomarkers could significantly impact diagnosis and an individualized, early treatment. Although the aetiology of ASD remains poorly understood, there is increasing evidence that neurotrophins and their receptors represent a group of candidate genes for ASD pathophysiology and biomarker research. Total messenger RNA (mRNA) from whole blood was obtained from adolescents and adults diagnosed as ASD (n = 21) according to DSM-IV criteria and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) algorithms, as well as healthy controls (n = 10). The mRNA expression of neurotrophins (BDNF, NT3 and NT4) and their receptors (TrkA, TrkB and p75 (NTR) ) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, social cognition abilities of ASD patients and controls were determined according to three Theory of Mind (ToM) tests (Reading the Mind in the Eyes, Faux pas, and Happé stories). The NT3 and NT4 mRNA expression in the whole blood was significantly lower in ASD compared to healthy controls, while p75(NTR) was higher (P < 0.005). In addition, lower scores in three of the ToM tests were observed in ASD subjects compared to controls. A significant (P < 0.005) ToM impairment in Happé stories test was demonstrated in ASD. Nevertheless, no correlations were observed between neurotrophins and their receptors expressions and measures of ToM. Given their potential as peripheral blood-based biomarkers, NT3, NT4 and p75 (NTR) mRNA expression patterns may be useful tools for a more personalized diagnostics and therapy in ASD. Further investigations with larger numbers of samples are needed to verify these results.

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Section: Discussionmentioning

confidence: 99%

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

et al. 2014

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“…Extracellular glutamate activates NMDA receptors (N-methyl-D-Aspartate) which then trigger the build up of excessive Ca 2+ in the cell . High amount of intracellular Ca 2+ leads to increased permeability of the mitochondrial membrane, followed by opening of its pores and activates caspase cascade resulted in apoptosis (Siniscalco, et al, 2012). Apoptosis in brain is associated with ASD as reported in post-mortem studies in which an increase of p53 transcription factor and drastic reduction of Bcl-2 anti-apoptotic protein were detected in the frontal cortex and cerebellum areas (Fatemi et al, 2001).…”

Section: Introductionmentioning

confidence: 95%

Monosodium Glutamate Exposure at Early Developmental Stage Increases Apoptosis and Stereotypic Behavior Risks on Zebrafish (Danio Rerio) Larvae

Kurnianingsih

2016

Indonesian J. Pharm.

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Excessive glutamate may give neurotoxic effects and contribute to Autism spectrum disorder(ASD). In this study, we investigated prolonged exposure effects of 10 µg/mL Monosodium Glutamate (MSG) on intracellular calcium level, bax, bcl-2, ratio of bax/bcl-2 genes expression, caspase-3, apoptosis of brain cells and stereotypic behavior of Zebrafish (Danio rerio) larvae at early developmental stages. Genes expression were determined by real time PCR, caspase-3 using ELISA, intracellular Ca 2+ and apoptotic cells of brain using confocal microscopy, locomotor activity by using crossing lines assay whereas stereotypic behavior by circle swimming. The results indicated that MSG exposure increased brain bax and bcl-2; and caspase-3; intracellular Ca 2+ ; and apoptosis; stereotypic behavior; and decreased locomotor activity. Termination of MSG treatments resulted in recovery of bax, bcl-2, caspase-3 basal levels and stereotypic behavior. In conclusion, MSG exposure at early embryonic stage increased brain cell damage and risk of behavior changes.

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“…This strong paracrine activity of MSCs seems to be the most plausible and reasonable mechanism for the functional benefit derived from MSC transplantation. Furthermore, transplanted MSCs can induce the host tissue to upregulate the production of anti-inflammatory molecules, such as IL-10, in this way restoring the pro-inflammatory processes noted in ASDs [39,40] .…”

Section: Mesenchymal Stem Cells In Treating Autism: the Rationalementioning

confidence: 99%

Mesenchymal stem cells in treating autism: Novel insights

Siniscalco

Bradstreet

Sych

et al. 2014

WJSC

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Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, abnormal to absent verbal communication, restricted interests, and repetitive stereotypic verbal and non-verbal behaviors, influencing the ability to relate to and communicate. The core symptoms of ASDs concern the cognitive, emotional, and neurobehavioural domains. The prevalence of autism appears to be increasing at an alarming rate, yet there is a lack of effective and definitive pharmacological options. This has created an increased sense of urgency, and the need to identify novel therapies. Given the growing awareness of immune dysregulation in a significant portion of the autistic population, cell therapies have been proposed and applied to ASDs. In particular, mesenchymal stem cells (MSCs) possess the immunological properties which make them promising candidates in regenerative medicine. MSC therapy may be applicable to several diseases associated with inflammation and tissue damage, where subsequent regeneration and repair is necessary. MSCs could exert a positive effect in ASDs through the following mechanisms: stimulation of repair in the damaged tissue, e.g. , inflammatory bowel disease; synthesizing and releasing anti-inflammatory cytokines and survival-promoting growth factors; integrating into existing neural and synaptic network, and restoring plasticity. The paracrine mechanisms of MSCs show interesting potential in ASD treatment. Promising and impressive results have been reported from the few clinical studies published to date, although the exact mechanisms of action of MSCs in ASDs to restore functions are still largely unknown. The potential role of MSCs in mediating ASD recovery is discussed in light of the newest findings from recent clinical studies.

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The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients

Cited by 64 publications

References 56 publications

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

Monosodium Glutamate Exposure at Early Developmental Stage Increases Apoptosis and Stereotypic Behavior Risks on Zebrafish (Danio Rerio) Larvae

Mesenchymal stem cells in treating autism: Novel insights

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