Demonstration of ameliorating effect of vardenafil through its anti-inflammatory and neuroprotective properties in autism spectrum disorder induced by propionic acid on rat model

Özkul, Bahattin; Urfalı, Furkan Ertürk; Sever, İbrahim Halil; Bozkurt, Mehmet Fatih; Söğüt, İbrahim; Elgörmüş, Çağrı Serdar; Erdoğan, Mümin Alper; Erbaş, Oytun

doi:10.1080/00207454.2022.2079507

Cited by 7 publications

(3 citation statements)

References 91 publications

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“…The pathophysiology of the disease is not yet fully understood, which causes difficulties in the treatment process. In addition, late diagnosis of the disease and the minor changes formed in the early period of the nervous system makes the treatment more difficult (Dogan et al, 2023;Özkul et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Although studies in recent years include environmental causes, autoimmune conditions, genetic causes, and inflammation in the central nervous system among the causes of autism, the leading cause has still not been fully discovered (Wei et al, 2011). Propionic acid (PPA) is one of the environmental agents that act by changing behavior and neuroinflammation (Dogan et al, 2023;Özkul et al, 2022). PPA is a volatile fatty acid and one of the crucial products of acidogenesis that is in the gastrointestinal system.…”

Section: Introductionmentioning

confidence: 99%

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The Therapeutic Effect of Bismuth Subsalicylate in a Propionic Acid-Induced Autism Model

Koenhemsi

Güneş

Eroğlu

et al. 2023

Preprint

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Backround and Aim: Autism is a clinically well-defined disorder that has no treatment yet. Other than behavior modification studies, medical treatments are still investigating. Rat is among the most frequently used experimental animals in such studies. Although various drugs cause autism in this animal species, propionic acid (PPA) was used in this study. Bismuth subsalicylate is frequently used in the treatment of gastrointestinal diseases in clinics and has anti-inflammatory and antacid effects. In our study, we examined the effects of bismuth in rats with autism using PPA. Materials and Methods: Thirty male rats were used in this study and 20 of them were given PPA intraperitoneally at 250 mg/kg/day for five days. Rats were randomly divided into three groups: Group 1 (no procedure was applied, n=10), Group 2 (intraperitoneal PPA+1 ml/kg/day % 0.9 salines given orally, n=10), and Group 3 (intraperitoneal PPA+60 mg/kg/day bismuth subsalicylate given orally, n = 10). After 15 days of treatment; behavioral tests, blood tests, and histopathology samples were taken. Results: A significant improvement was observed in autism-like behaviors in rats treated with bismuth. Tumor necrosis factor-alpha (TNF-α), Interleukin-17 (IL-17), IL-6, prostaglandin E2 (PGE2), and malondialdehyde (MDA) levels decreased, and brain-derived neurotrophic factor (BDNF) levels increased in the bismuth group. Conclusion: This study showed that bismuth can be used in addition to other treatments for autism. However, further studies on the subject are needed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Therapeutic Effect of Bismuth Subsalicylate in a Propionic Acid-Induced Autism Model

Koenhemsi

Güneş

Eroğlu

et al. 2023

Preprint

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“…Propionic acid (PPA) is widely used to model mitochondrial dysfunction in neurons and has been shown to disrupt mitochondrial membrane potential, biogenesis, and respiration in vitro [31][32][33][34][35]. PPA is known to impair neuronal metabolism and alter behavior in vivo and is an established animal model to study neurodevelopmental mechanisms involved in autism spectrum disorder (ASD) [36][37][38][39][40][41][42][43][44]. However, the effect of PPA on mitochondrial morphology and dynamics remains understudied.…”

Section: Introductionmentioning

confidence: 99%

Transmission Electron Microscopy Reveals Propionic Acid-induced Alterations to Mitochondrial Morphology in SH-SY5Y Cells

Buchanan¹,

Mahony²,

Bam³

et al. 2022

Preprint

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Mitochondrial dysregulation is implicated in numerous neurological disorders. Mitochondrial dynamics, including biogenesis, fusion and fission, are essential components of mitostasis which is modulated by complex regulatory mechanisms. Although expression studies are often used to investigate mitochondrial dynamics, these studies may be limited by the interdependent and temporal nature of mitostasis. Transmission electron microscopy (TEM) and cryogenic preparation methods provide a direct approach to examine mitochondrial ultrastructure in neurons. We investigated the utility of TEM to visualize mitochondrial morphological changes in SH-SY5Y cells treated with propionic acid (PPA). We examined whether morphological alterations were associated with differences in membrane potential or expression of biogenesis, fusion and fission genes. PPA induced a significant decrease in mitochondrial area (p<0.01 5mM), Feret's diameter and perimeter (p<0.05 5mM), and in area2 (p<0.05 3mM, p<0.01 5mM) – consistent with a shift towards fission. Morphological changes were not associated with significant differences in mitochondrial membrane potential. However, we observed decreased gene expression of NRF1 (p<0.01), TFAM (p<0.05), and STOML2 (p<0.0001). These data support a disruption of the balance in dynamics to preserve function under stress. This demonstrates the utility of TEM to provide insight into mitochondrial dynamics and function which can inform targeted mechanistic investigations into neuropathology.

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Amelioration of propionic acid‐induced autism‐like behaviors in rats by fenofibrate: A focus on reduction of brain galectin‐3 levels

Erdogan,

Akbulut,

Altuntaş

et al. 2024

Intl J of Devlp Neuroscience

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IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. This study examines the effects of fenofibrate on a propionic acid (PPA)‐induced rat model of ASD, focusing on behavioral changes, inflammatory markers, and histological findings.Materials and MethodsThirty male Wistar rats were divided into three groups: a control group, a group receiving PPA and saline, and a group treated with PPA and fenofibrate for 15 days. Behavioral assessments, including the three‐chamber sociability test, open‐field test, and passive avoidance learning, were conducted. Biochemical analyses measured TNF‐α, NGF, IL‐17, IL‐2, and galectin‐3 levels in brain tissues. Histological evaluations focused on Purkinje neuron counts in the cerebellum and neuronal changes in the CA1 and CA3 regions of the hippocampus, along with glial fibrillary acidic protein (GFAP) levels.ResultsFenofibrate treatment significantly improved behavioral outcomes, reducing autism‐like behaviors compared to the PPA/saline group. Biochemically, the PPA/saline group showed elevated levels of malondialdehyde, TNF‐α, IL‐2, IL‐17, and galectin‐3, which were reduced following fenofibrate treatment. Histologically, the PPA/saline group exhibited fewer, dysmorphic Purkinje neurons and increased glial activity in the CA1 region, both of which were ameliorated by fenofibrate treatment.ConclusionFenofibrate shows promise in mitigating autism‐like behaviors in a rat model of ASD, likely due to its antioxidative and neuroprotective properties, which contribute to preserving neuronal integrity and reducing inflammation.

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Demonstration of ameliorating effect of vardenafil through its anti-inflammatory and neuroprotective properties in autism spectrum disorder induced by propionic acid on rat model

Cited by 7 publications

References 91 publications

The Therapeutic Effect of Bismuth Subsalicylate in a Propionic Acid-Induced Autism Model

The Therapeutic Effect of Bismuth Subsalicylate in a Propionic Acid-Induced Autism Model

Transmission Electron Microscopy Reveals Propionic Acid-induced Alterations to Mitochondrial Morphology in SH-SY5Y Cells

Amelioration of propionic acid‐induced autism‐like behaviors in rats by fenofibrate: A focus on reduction of brain galectin‐3 levels

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