The role of apitoxin in alleviating propionic acid-induced neurobehavioral impairments in rat pups: The expression pattern of Reelin gene

Daghestani, Maha H.; Selim, Mohammed; Abd‐Elhakim, Yasmina M.; Said, Enas N.; El-Hameed, Noura E. Abd; Khalil, Samah R.; El-Tawil, Osama S.

doi:10.1016/j.biopha.2017.06.034

Cited by 32 publications

(9 citation statements)

References 70 publications

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“…These results indicate long-lasting (>4 weeks) effects of the initial 3-day treatment of PPA. This is in parallel with other studies using PPA treatment, which also report social impairment measured more than four weeks after the initial PPA treatment [22,[49][50][51]. PPA animals also exhibited an increased immobility time compared to the control animals (Figure 2C), which might indicate an increased anxiety-like behavior, which is a behavioral feature of ASD models [27,49].…”

Section: Discussionsupporting

confidence: 88%

Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism

et al. 2021

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Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut–brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.

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Section: Discussionsupporting

confidence: 88%

Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism

et al. 2021

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“…El-Ansary et al [1] designed a rodent model of autism by inducing persistent biochemical autistic features by oral administration of PPA in rat pups, including oxidative stress, neuro-inflammation, altered neurochemistry, and impaired energy and lipid metabolism. Recently, the same model with identical dose and mode of administration of PPA was effective in inducing several behavioral abnormalities, such as social interaction impairment, hyperactivity, and repetitive behaviors, together with histopathological changes such as neuronal loss and astrogliosis [2, 3]. This finding supports the use of PPA in animal models of autism.…”

Section: Introductionmentioning

confidence: 64%

Comparative study on the independent and combined effects of omega-3 and vitamin B12 on phospholipids and phospholipase A2 as phospholipid hydrolyzing enzymes in PPA-treated rats as a model for autistic traits

et al. 2018

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BackgroundAbnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism.MethodsThe present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies. Five groups of rats were selected: Group 1 was the control. Group 2 was the rodent model of autism treated with a neurotoxic dose of PPA. Group 3 was given vitamin B12 cobalamin (16.7 mg/kg/day) for 30 days after PPA treatment. Group 4 was given pharmaceutical grade Omega-3 (200 mg cholesterol free-DHA/kg body weight/day), a product of Madre lab, Germany, for 30 days after PPA treatment for 3 days. Group 5 was given a combined dose of ω-3 + Vitamin B12 for the same duration post-PPA treatment. Phospholipid levels and Phospholipase A2 were measured in the brain homogenates of all the groups. ELISA and western blotting were used to detect the cPLA2 protein level.ResultsA significant decrease in phospholipid levels and a significant increase in cPLA2 were found in brain tissue of PPA-treated rats; however, both ω-3 and vitamin B12 were efficient in ameliorating the neurotoxic effect of PPA.ConclusionBoth ω-3 and vitamin B12 may play a role in ameliorating impaired phospholipid metabolism in autism; however, proper clinical trials are needed.

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“…In contrast, female offspring of rats prenatally exposed to PPA were significantly more active than vehicle-treated females (Foley et al, 2014). PPA-provoked hyperlocomotion was also described in a number of recent studies performed on young rats (Daghestani et al, 2017;Mirza & Sharma, 2018). Such contradictory results need further evaluation but may relate to the different behaviour paradigms, leading to increased anxiety-like behaviours via increased swimming, in the MWM, or decreased motor activity in the MBM and OF.…”

Section: Discussionmentioning

confidence: 91%

Behavioural and brain ultrastructural changes following the systemic administration of propionic acid in adolescent male rats. Further development of a rodent model of autism

Lobzhanidze

Japaridze²,

Lordkipanidze

et al. 2020

Intl J of Devlp Neuroscience

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Short chain fatty acids, produced as gut microbiome metabolites but also present in the diet, exert broad effects in host physiology. Propionic acid (PPA), along with butyrate and acetate, plays a growing role in health, but also in neurological conditions. Increased PPA exposure in humans, animal models and cell lines elicit diverse behavioural and biochemical changes consistent with organic acidurias, mitochondrial disorders and autism spectrum disorders (ASD). ASD is considered a disorder of synaptic dysfunction and cell signalling, but also neuroinflammatory and neurometabolic components. We examined behaviour (Morris water and radial arm mazes) and the ultrastructure of the hippocampus and medial prefrontal cortex (electron microscopy) following a single intraperitoneal (i.p.) injection of PPA (175 mg/kg) in male adolescent rats. PPA treatment showed altered social and locomotor behaviour without changes in learning and memory. Both transient and enduring ultrastructural alterations in synapses, astro‐ and microglia were detected in the CA1 hippocampal area. Electron microscopic analysis showed the PPA treatment significantly decreased the total number of synaptic vesicles, presynaptic mitochondria and synapses with a symmetric active zone. Thus, brief systemic administration of this dietary and enteric short chain fatty acid produced behavioural and dynamic brain ultrastructural changes, providing further validation of the PPA model of ASD.

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The role of apitoxin in alleviating propionic acid-induced neurobehavioral impairments in rat pups: The expression pattern of Reelin gene

Cited by 32 publications

References 70 publications

Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism

Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism

Comparative study on the independent and combined effects of omega-3 and vitamin B12 on phospholipids and phospholipase A2 as phospholipid hydrolyzing enzymes in PPA-treated rats as a model for autistic traits

Behavioural and brain ultrastructural changes following the systemic administration of propionic acid in adolescent male rats. Further development of a rodent model of autism

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