Atorvastatin Improves the Propionic Acid-Induced Autism in Rats: The Roles of Sphingosine-1-Phosphate and Anti-inflammatory Action

Durankuş, Ferit; Budak, Korkut; Albayrak, Yakup; Sever, İbrahim Halil; Özkul, Bahattin; Uyanıkgil, Yiğit; Albayrak, Neslihan; Erbaş, Oytun

doi:10.7759/cureus.36870

Cited by 3 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, lovastatin is known to inhibit ERK and downstream mTOR1 (77), and recently administration of atorvastatin to an animal model of ASD has decreased inflammation and oxidative stress reflected in brain levels of IL-2, IL-17, TNF-α, lactate and malondialdehyde, as well as increased levels of sphingosine-1-phosphate, nerve growth factor (NGF) and number of neurons in hippocampus and cerebellum (78).…”

Section: Discussionmentioning

confidence: 99%

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Stancioiu¹,

Bogdan²,

Dumitrescu³

2023

Preprint

View full text Add to dashboard Cite

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1-2% in most countries. Its complex causality – a combination of genetic, immune, metabolic and environmental factors - is translated into pleiomorphic developmental disorders of various severity, which have in common two main aspects: repetitive, restrictive behaviors, and difficulties in social interaction varying from awkward habits and verbalization to complete lack of interest from the ASD child for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator – a disease biomarker and medication – and currently there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy.It is known that inflammation is present in a majority of ASD children, and blood inflammatory markers, together with metabolic, electrophysiological markers and imagistics are useful for ASD diagnostic validation and treatment; however, they tend to leave out a sizeable proportion of ASD kids who do not have such modifications. Genetic testing – whole exome sequencing or targeted profiling on about 500 ASD-linked genes- may also provide good insight into pathophysiology, however many times its results are more restrictive rather than offering additional therapeutic options.Here we describe a new biomarker for ASD - the neuron-specific enolase (NSE) - which was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation and therapeutic intervention for ASD kids.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Stancioiu¹,

Bogdan²,

Dumitrescu³

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Also, astrocytes control membrane integrity (including synaptic vesicles) by clearing peroxides produced from lipid degradation of membranes, and they are involved in synaptic formation and transmission [ 82 ]. In this context, lovastatin is known to inhibit ERK and downstream mTOR1 [ 83 ], and recently, administration of atorvastatin to an animal model of ASD has decreased inflammation and oxidative stress reflected in the brain levels of IL-2, IL-17, TNF-α, lactate, and malondialdehyde, as well as the increased levels of the sphingosine-1-phosphate, the nerve growth factor (NGF), and the number of neurons in the hippocampus and cerebellum [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Stancioiu¹,

Bogdan

Dumitrescu

2023

Life

View full text Add to dashboard Cite

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1–2% in most countries. Its complex causality—a combination of genetic, immune, metabolic, and environmental factors—is translated into pleiomorphic developmental disorders of various severity, which have two main aspects in common: repetitive, restrictive behaviors and difficulties in social interaction varying from awkward habits and verbalization to a complete lack of interest for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator—a disease biomarker and medication—and currently, there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy. In the CORDUS clinical study, we have administered autologous cord blood to ASD kids who had little or no improvement after other treatments and searched for a biomarker which could help predict the degree of improvement in each patient. We have found that the neuron-specific enolase (NSE) was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation, and therapeutic intervention for ASD kids.

show abstract

Adverse neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with statins

Al-Shalchi,

Mohammad

2024

Vet World

View full text Add to dashboard Cite

Background and Aim: Pleiotropic effects of hypolipidemic statins with behavioral outcomes have been suggested in humans and laboratory animals. There is limited information on the neurobehavioral effects of statins in mice. The aim of the present study was to examine changes in neurobehavioral performance and cholinesterase (ChE) activity in mice after high doses of three commonly used statins (atorvastatin, simvastatin, and rosuvastatin). Materials and Methods: Two hours after vehicle (control) or statin dosing at 250, 500, 750, or 1000 mg/kg orally, each mouse was subjected to 5 min open-field activity, negative geotaxis at an angle of 45°/60 s, 5 min head pocking, and forced swimming endurance. Plasma, erythrocyte, and brain ChE activities were determined spectrophotometrically 2 and 24 h after oral dosing of statins at 500 and 1000 mg/kg. Results: The statins variably, but dose-dependently and significantly (p < 0.05) delayed the latency to move in the open-field arena, decreased locomotion and rearing, reduced head pocking, and delayed negative geotaxis performance. However, statins significantly increased the duration of forced swimming and decreased the duration of immobility in the swimming tank. Statins significantly and dose-dependently decreased plasma, erythrocyte, and brain ChE activity 2 and 24 h after dosing. Plasma and brain ChE activities recovered by 5%–32.9% and 5.7%–14.4% 24 h later from the 2 h ChE values, respectively. Conclusion: High doses of statins differentially modulate neurobehavioral outcomes in mice in association with reduced plasma, erythrocyte, and brain ChE activity. Plasma or erythrocyte ChE may be used for biomonitoring of the adverse/ therapeutic effects of statins. Keywords: atorvastatin, head pocking, negative geotaxis, open-field activity, rosuvastatin, simvastatin, swimming endurance.

show abstract

Atorvastatin Improves the Propionic Acid-Induced Autism in Rats: The Roles of Sphingosine-1-Phosphate and Anti-inflammatory Action

Cited by 3 publications

References 30 publications

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Adverse neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with statins

Contact Info

Product

Resources

About