Chronic acetyl-L-carnitine treatment alleviates behavioral deficits and neuroinflammation through enhancing microbiota derived-SCFA in valproate model of autism

Zahedi, Elham; Sadr, Seyed Shahabeddin; Sanaeierad, Ashkan; Roghani, Mehrdad

doi:10.1016/j.biopha.2023.114848

Cited by 17 publications

(5 citation statements)

References 51 publications

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“…Megamonas, a genus of bene cial bacteria belonging to the Firmicutes phylum [49], is involved in the metabolism of the organism through the fermentation of carbohydrates to produce short-chain fatty acids (SCFA) [50]. These SCFAs, such as acetate, propionate, and butyrate, are essential for maintaining intestinal homeostasis [51,52]and have been shown to have signi cant anti-in ammatory effects in various in ammatory diseases [53][54][55]. Jing et al demonstrated that supplementation with short-chain fatty acids (SCFA) led to the down-regulation of the NF-κB signaling pathway, resulting in decreased in ammation and improved neural tissue function [56].…”

Section: Discussionmentioning

confidence: 99%

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

He,

Luo,

et al. 2024

Preprint

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Background: Numerous studies have indicated a correlation between the gut microbiota (GM) and acute pancreatitis (AP), yet the precise causal relationship between them remains ambiguous. Methods: A two-sample Mendelian randomization (MR) study was conducted utilizing aggregated data from genome-wide association studies (GWASs) of 471 taxa (11 phyla, 19 orders, 24 orders, 62 families, 146 genera, and 209 species) and AP patients. Various methods, including inverse variance weighting (IVW), MR‒Egger, weighted medians, simple mode, and weighted mode, were employed to assess the causal association between the GM and AP. Sensitivity analyses were conducted utilizing Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO, followed by reverse MR analysis to evaluate the potential reverse causality between AP and GM. Results: Three gut microbial taxa were found to have significant associations with acute pancreatitis (AP). The inverse variance weighted (IVW) results revealed that Coprobacillus (OR 1.19, 95% CI 1.01 to 1.40, p=0.035) and Holdemania sp900120005 (OR 1.18, 95% CI 1.02 to 1.35, p=0.023) were identified as risk factors for the development of AP, while Megamonas (OR: 0.87, 95% CI: 0.77 to 0.98, p=0.023) was found to be a protective factor against the occurrence of AP. A thorough sensitivity analysis confirmed the reliability of our findings. Reverse Mendelian randomization (MR) analysis did not indicate any causal relationship between AP and the gut microbiota (GM). Conclusions: This study revealed a complex causal relationship between 3 GM taxa and AP, providing new evidence for the development of AP from a genetic perspective.

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Section: Discussionmentioning

confidence: 99%

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

He,

Luo,

et al. 2024

Preprint

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“…Following successful mating (Fig. 8 a), female rats were randomly divided into two groups: one group received vehicle, while the other group received an intraperitoneal injection of 600 mg/kg of VPA (Darou Pakhsh Co., Tehran, Iran) at 12.5 days after successful mating 50 . One of the side effects of VPA on 100% of rat offspring is a twisted tail observed at one or several locations, as shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles

Afshari,

Gharibzadeh,

Pouretemad

et al. 2024

Sci Rep

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Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.

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“…In a valproate-induced animal model autism, the researchers found that the content of SCFAs in ASD animals was decreased and intestinal tissue disintegration was observed, accompanied by increased levels of the pro-inflammatory factor TNF-α, while the abundance of microglia was increased. At the same time, the experimental results indicate that acetyl-L-carnitine can increase the content of acetic acid and butyric acid in animals and achieve the effect of ameliorating behavioral disorders [ 174 ]. According to research, more than 25% of children with ASD have elevated levels of serotonin in their blood, suggesting a link between serotonin and ASD[ 175 ].…”

Section: The Role and Influence Of Gut Metabolites In Neuroinflammati...mentioning

confidence: 99%

Gut Metabolites Acting on the Gut-Brain Axis: Regulating the Functional State of Microglia

Deng¹,

Yi²,

Xiong³

et al. 2024

Aging and disease

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The gut-brain axis is a communication channel that mediates a complex interplay of intestinal flora with the neural, endocrine, and immune systems, linking gut and brain functions. Gut metabolites, a group of small molecules produced or consumed by biochemical processes in the gut, are involved in central nervous system regulation via the highly interconnected gut-brain axis affecting microglia indirectly by influencing the structure of the gut-brain axis or directly affecting microglia function and activity. Accordingly, pathological changes in the central nervous system are connected with changes in intestinal metabolite levels as well as altered microglia function and activity, which may contribute to the pathological process of each neuroinflammatory condition. Here, we discuss the mechanisms by which gut metabolites, for instance, the bile acids, short-chain fatty acids, and tryptophan metabolites, regulate the structure of each component of the gut-brain axis, and explore the important roles of gut metabolites in the central nervous system from the perspective of microglia. At the same time, we highlight the roles of gut metabolites affecting microglia in the pathogenesis of neurodegenerative diseases and neurodevelopmental disorders. Understanding the relationship between microglia, gut microbiota, neuroinflammation, and neurodevelopmental disorders will help us identify new strategies for treating neuropsychiatric disorders.

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Chronic acetyl-L-carnitine treatment alleviates behavioral deficits and neuroinflammation through enhancing microbiota derived-SCFA in valproate model of autism

Cited by 17 publications

References 51 publications

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

A bidirectional two-sample Mendelian randomization using the gut microbiota to reveal potential therapeutic targets for acute pancreatitis

Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles

Gut Metabolites Acting on the Gut-Brain Axis: Regulating the Functional State of Microglia

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