Resveratrol Treatment of Autism Spectrum Disorder—A Pilot Study

Marchezan, Josemar; Deckmann, Iohanna; Fonseca, Guilherme Cordenonsi da; Margis, Rogério; Riesgo, Rudimar dos Santos; Gottfried, Carmem

doi:10.1097/wnf.0000000000000516

Cited by 6 publications

(4 citation statements)

References 43 publications

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“…Considered together, our results confirm that a lack of Nrf2 signaling in adult BTBR mice after exposure to methylmercury during the juvenile stage might be responsible for the worsening of autism-like behavior. Several Nrf2 activators such as resveratrol, sulforaphane, curcumin, and naringenin showed improvements in autistic behavior both in human ASD subjects and mice models of autism which suggests that Nrf2 signaling plays a key role in the amplification of the antioxidant defenses required to protect against oxidant-stress induced by various toxicants/pollutants [ 27 , 53 , 54 , 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Exposure to Methylmercury at Juvenile Stage Worsens Autism-like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain

Algahtani

Ahmad

Al-Kharashi

et al. 2023

Toxics

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Autism spectrum disorder (ASD) is a multifaceted developmental condition that first appears in infancy. The condition is characterized by recurrent patterns in behavior and impairments in social and vocalization abilities. Methylmercury is a toxic environmental pollutant, and its derivatives are the major source of organic mercury to human beings. Inorganic mercury, which is released from a variety of pollutants into oceans, rivers, and streams, is transformed into methylmercury by bacteria and plankton in the water, which later builds up in fish and shellfish, and then enters humans through the consumption of fish and shellfish and increases the risk of developing ASD by disturbing the oxidant–antioxidant balance. However, there has been no prior research to determine the effect of juvenile exposure of methylmercury chloride on adult BTBR mice. Therefore, the current study evaluated the effect of methylmercury chloride administered during the juvenile stage on autism-like behavior (three-chambered sociability, marble burying, self-grooming tests) and oxidant–antioxidant balance (specifically Nrf2, HO-1, SOD-1, NF-kB, iNOS, MPO, and 3-nitrotyrosine) in the peripheral neutrophils and cortex of adult BTBR and C57BL/6 (B6) mice. Our results show that exposure to methylmercury chloride at a juvenile stage results in autism-like symptoms in adult BTBR mice which are related to a lack of upregulation of the Nrf2 signaling pathway as demonstrated by no significant changes in the expression of Nrf2, HO-1, and SOD-1 in the periphery and cortex. On the other hand, methylmercury chloride administration at a juvenile stage increased oxidative inflammation as depicted by a significant increase in the levels of NF-kB, iNOS, MPO, and 3-nitrotyrosine in the periphery and cortex of adult BTBR mice. This study suggests that juvenile exposure to methylmercury chloride contributes to the worsening of autism-like behavior in adult BTBR mice through the disruption of the oxidant–antioxidant balance in the peripheral compartment and CNS. Strategies that elevate Nrf2 signaling may be useful to counteract toxicant-mediated worsening of ASD and may improve quality of life.

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Section: Discussionmentioning

confidence: 99%

Exposure to Methylmercury at Juvenile Stage Worsens Autism-like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain

Algahtani

Ahmad

Al-Kharashi

et al. 2023

Toxics

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“…RSV has been investigated in adults of all ages including elderly populations over 70 years, as illustrated by the frequency distribution of mean age per group for individuals that received RSV in each trial (Figure 5B). Furthermore, four separate trials have been conducted in children, assessing the ability of RSV to affect symptoms associated with attention-deficit/hyperactivity disorder [106], autism spectrum disorder [105,149], and fast breathing pneumonia [138].…”

Section: Clinical Indication and Trial Participantsmentioning

confidence: 99%

Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities

Brown,

Theofanous,

Britton

et al. 2024

IJMS

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Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current ‘state-of-play’ and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol’s potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.

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“…Glioprotective strategies may attenuate these abnormalities, particularly because mood disorders are glial disorders resveratrol, a well-tested glioprotective molecule, presents efficacy, tolerability, and safety, as well as anti-inflammatory, antioxidant, and neuroprotective properties, emerging as a promising therapeutic strategy for large-scale studies in autism spectrum disorder, as well as in schizophrenia. 118 Resveratrol can also protect neurons in brain-implantable electrodes, such as those used in deep brain stimulation. 119 In this regard, glioprotective molecules can result in an overall improvement in CNS functioning, including during glial damage associated with long-term use of antipsychotics in neuropsychiatric disorders.…”

Section: Could Glioprotective Molecules Attenuate Neuropsychiatric Di...mentioning

confidence: 99%

Section: Could Glioprotective Molecules Attenuate Neuropsychiatric Di...mentioning

confidence: 99%

The Janus face of antipsychotics in glial cells: Focus on glioprotection

Schmitz,

da Silva,

Bobermin

et al. 2023

Exp Biol Med (Maywood)

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Antipsychotics are commonly prescribed to treat several neuropsychiatric disorders, including schizophrenia, mania in bipolar disorder, autism spectrum disorder, delirium, and organic or secondary psychosis, for example, in dementias such as Alzheimer’s disease. There is evidence that typical antipsychotics such as haloperidol are more effective in reducing positive symptoms than negative symptoms and/or cognitive deficits. In contrast, atypical antipsychotic agents have gained popularity over typical antipsychotics, due to fewer extrapyramidal side effects and their theoretical efficacy in controlling both positive and negative symptoms. Although these therapies focus on neuron-based therapeutic schemes, glial cells have been recognized as important regulators of the pathophysiology of neuropsychiatric disorders, as well as targets to improve the efficacy of these drugs. Glial cells (astrocytes, oligodendrocytes, and microglia) are critical for the central nervous system in both physiological and pathological conditions. Astrocytes are the most abundant glial cells and play important roles in brain homeostasis, regulating neurotransmitter systems and gliotransmission, since they express a wide variety of functional receptors for different neurotransmitters. In addition, converging lines of evidence indicate that psychiatric disorders are commonly associated with the triad neuroinflammation, oxidative stress, and excitotoxicity, and that glial cells may contribute to the gliotoxicity process. Conversely, glioprotective molecules attenuate glial damage by generating specific responses that can protect glial cells themselves and/or neurons, resulting in improved central nervous system (CNS) functioning. In this regard, resveratrol is well-recognized as a glioprotective molecule, including in clinical studies of schizophrenia and autism. This review will provide a summary of the dual role of antipsychotics on neurochemical parameters associated with glial functions and will highlight the potential activity of glioprotective molecules to improve the action of antipsychotics.

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Resveratrol Treatment of Autism Spectrum Disorder—A Pilot Study

Cited by 6 publications

References 43 publications

Exposure to Methylmercury at Juvenile Stage Worsens Autism-like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain

Exposure to Methylmercury at Juvenile Stage Worsens Autism-like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain

Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities

The Janus face of antipsychotics in glial cells: Focus on glioprotection

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