Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats

Kumar, Hariom; Sharma, Bhupesh

doi:10.1016/j.brainres.2015.10.052

Cited by 86 publications

(61 citation statements)

References 57 publications

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“…The potential role of the microbiome in ASD also gains strong support from several animal studies that have modulated social behaviors through dysbiosis, and ameliorated those symptoms with restoration of gut microbes [Buffington et al, ; Kumar & Sharma, ]. Parallel findings have even been reported in humans with ASD.…”

Section: Introductionmentioning

confidence: 82%

“…In the context of recent studies highlighting the genetic contributions to ASD [Sandin et al, ], it is unlikely that microbial shifts represent the sole driver of autistic behavior. However, alterations in the microbiome have been linked with atypical social, communicative, and repetitive behavior in animal models [Buffington et al, ; Kumar & Sharma, ]. One mechanism for this link may be metabolomic disruptions [De Angelis et al, ].…”

Section: Discussionmentioning

confidence: 99%

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Oral microbiome activity in children with autism spectrum disorder

Hicks

Uhlig²,

Afshari

et al. 2018

Autism Research

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Autism spectrum disorder (ASD) is associated with several oropharyngeal abnormalities, including buccal sensory sensitivity, taste and texture aversions, speech apraxia, and salivary transcriptome alterations. Furthermore, the oropharynx represents the sole entry point to the gastrointestinal (GI) tract. GI disturbances and alterations in the GI microbiome are established features of ASD, and may impact behavior through the "microbial-gut-brain axis." Most studies of the ASD microbiome have used fecal samples. Here, we identified changes in the salivary microbiome of children aged 2-6 years across three developmental profiles: ASD (n = 180), nonautistic developmental delay (DD; n = 60), and typically developing (TD; n = 106) children. After RNA extraction and shotgun sequencing, actively transcribing taxa were quantified and tested for differences between groups and within ASD endophenotypes. A total of 12 taxa were altered between the developmental groups and 28 taxa were identified that distinguished ASD patients with and without GI disturbance, providing further evidence for the role of the gut-brain axis in ASD. Group classification accuracy was visualized with receiver operating characteristic curves and validated using a 50/50 hold-out procedure. Five microbial ratios distinguished ASD from TD participants (79.5% accuracy), three distinguished ASD from DD (76.5%), and three distinguished ASD children with/without GI disturbance (85.7%). Taxonomic pathways were assessed using the Kyoto Encyclopedia of Genes and Genomes microbial database and compared with one-way analysis of variance, revealing significant differences within energy metabolism and lysine degradation. Together, these results indicate that GI microbiome disruption in ASD extends to the oropharynx, and suggests oral microbiome profiling as a potential tool to evaluate ASD status. Autism Res 2018, 11: 1286-1299. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Previous research suggests that the bacteria living in the human gut may influence autistic behavior. This study examined genetic activity of microbes living in the mouth of over 300 children. The microbes with differences in children with autism were involved in energy processing and showed potential for identifying autism status.

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Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Oral microbiome activity in children with autism spectrum disorder

Hicks

Uhlig²,

Afshari

et al. 2018

Autism Research

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“…Particular case studies also link antibiotic treatment to improvements in ASD behaviors and co-morbid conditions (51). In addition, the antibiotics d-cycloserine and minocycline are promising in light of their ability to treat behavioral symptoms of ASD in clinical trials and animal models (52–54). While both antibiotics are used to treat infections, their neuroprotective effects are commonly attributed to their roles as partial NMDA receptor agonist and microglial activation inhibitor, respectively.…”

Section: Potential Roles For the Microbiome In Asdmentioning

confidence: 99%

Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder

Vuong

Hsiao

2017

Biological Psychiatry

467

330

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Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that affects one in 45 children in the United States, with a similarly striking prevalence in countries around the world. However, mechanisms underlying its etiology and manifestations remain poorly understood. While ASD is diagnosed based on the presence and severity of impaired social communication and repetitive behavior, immune dysregulation and gastrointestinal issues are common co-morbidities. The microbiome is an integral part of human physiology; recent studies show that changes in the gut microbiota can modulate gastrointestinal physiology, immune function and even behavior. Links between particular bacteria from the indigenous gut microbiota and phenotypes relevant to ASD raise the important question of whether microbial dysbiosis plays a role in the development or presentation of ASD symptoms. Here we review reports of microbial dysbiosis in ASD. We further discuss potential effects of the microbiota on ASD-associated symptoms, drawing upon signaling mechanisms for reciprocal interactions between the microbiota, immunity, gut function and behavior. In addition, we discuss recent findings supporting a role for the microbiome as an interface between environmental and genetic risk factors that are associated with ASD. These studies highlight the integration of pathways across multiple body systems that together can impact brain and behavior and suggest that changes in the microbiome may contribute to symptoms of neurodevelopmental disease.

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“…showed that prenatal treatment with minocycline led to recovery of microglial activation markers as well as improved anxiety behaviors. In VPA-induced rat ASD model, minocycline was also shown to improve autistic behaviors 11). Minocycline has also been shown promising in few yet accumulating human trials.…”

Section: Immunomodulatory Treatmentmentioning

confidence: 99%

Microglia and Autism Spectrum Disorder: Overview of Current Evidence and Novel Immunomodulatory Treatment Options

Kim

Hong

Bae

2018

Clin Psychopharmacol Neurosci

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Autism spectrum disorder is a rapidly increasing heterogeneous neurodevelopmental syndrome, remarked by persistent deficit in social communication, and restricted, repetitive patterns of behavior and interest. Lately, maternal immune activation and micgroglial dysfunction in the developing brain have been gaining mounting evidence and leading to studies of various novel agents as potential treatment options. A few immunomodulatory treatment options—luteolin, minocycline, suramin, vitamin D, gut microbiota—are discussed in the current article, regarding the current understanding of their mechanisms and evidence for potential clinical use. More studies are warranted to understand their exact mechanisms of action and to verify efficacy and safety in human subjects.

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Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats

Cited by 86 publications

References 57 publications

Oral microbiome activity in children with autism spectrum disorder

Oral microbiome activity in children with autism spectrum disorder

Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder

Microglia and Autism Spectrum Disorder: Overview of Current Evidence and Novel Immunomodulatory Treatment Options

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