A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

MacFabe, Derrick F.; Rodríguez-Capote, Karina; Hoffman, Jennifer; Franklin, Andrew E.; Mohammad-Asef, Yalda; Taylor, Alison R.; Boon, Francis; Cain, Donald P.; Kavaliers, Martin; Possmayer, Fred; Ossenkopp, Klaus‐Peter

doi:10.3844/ajbbsp.2008.146.166

Cited by 97 publications

(79 citation statements)

References 140 publications

(166 reference statements)

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“…Previous studies in rats by MacFabe et al have shown that intraventricular administration of propionate induces behaviors resembling autism (e.g., repetitive dystonic behaviors, retropulsion, seizures, and social avoidance) (12,13). We have also reported increased fecal propionate concentrations in ASD children compared with that in controls in the same fecal samples (25).…”

Section: Vol 77 2011 Lower Abundance Of a Muciniphila In Asd Childsupporting

confidence: 55%

Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism

Christophersen

Sorich

et al. 2011

Appl Environ Microbiol

361

264

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Gastrointestinal disturbance is frequently reported for individuals with autism. We used quantitative real-time PCR analysis to quantify fecal bacteria that could influence gastrointestinal health in children with and without autism. Lower relative abundances of Bifidobacteria species and the mucolytic bacterium Akkermansia muciniphila were found in children with autism, the latter suggesting mucus barrier changes.Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder where gastrointestinal (GI) disturbance is commonly reported (11). Evidence is emerging that the profiles of the GI microbiota (8,9,16,22) and fermentation products (2, 28) in individuals with ASD are different from those of the general population. Finegold et al. (9) have reported a relationship between regressive autism and altered GI microbiota. Indeed, the modulation of intestinal microbiota in children with ASD through the use of antibiotics (19) and probiotics such as Lactobacillus plantarum WCSF1 (17) has been shown to improve behavior and bowel health outcomes. In this study, various GI bacteria, including Clostridium spp., members of the Bacteroides fragilis group, Akkermansia muciniphila, and Prevotella species, which are emerging as important markers of GI health, were examined in children with ASD, their siblings, and community controls. We also investigated whether correlations exist between GI microbial abundances and the presence or absence of caregiver-reported functional GI disorders (FGIDs) in children with ASD.The inclusion criteria for participants were as previously described (26). Briefly, fecal samples were collected from children with ASD (n ϭ 23), recruited through Autism SA, who were diagnosed by a multidisciplinary team using the childhood autism rating scale (20) and/or the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (3). The ASD participants were diagnosed with autistic disorder (n ϭ 17) and Asperger's syndrome (n ϭ 6), and all but three participants were reported to have a regressive form of autism. Children who met the criteria for ASD but presented with a comorbid diagnosis of a chromosomal abnormality were excluded from the study. We also recruited 22 typically developing siblings (SIB) of the ASD cohort as well as 9 unrelated community controls (CON) without a family history of autism as two different control groups. The CON participants were eligible to participate if they did not have a sibling or first cousin with ASD. Participants' caregivers were required to complete a functional gastrointestinal disorder (FGID) questionnaire (21) and a questionnaire that investigated medication use.Fresh fecal specimens were collected from participants over a 48-h period to exclude day-to-day variability. Each bowel movement was collected in a separate bag and frozen immediately in a portable freezer and stored at Ϫ20°C. Specimens were transported to the laboratory in freezers and stored at Ϫ80°C until they were processed. Specimens were defrosted at room temperature, and all processing was...

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Section: Vol 77 2011 Lower Abundance Of a Muciniphila In Asd Childsupporting

confidence: 55%

Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism

Christophersen

Sorich

et al. 2011

Appl Environ Microbiol

361

264

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“…The formaldehyde produced was measured colorimetrically with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole as the chromogen. 23 Catalase activity was expressed as mg ⅐ nM Ϫ1 ⅐ min Ϫ1 protein.…”

Section: Measurement Of Malondialdehyde Superoxide Dismutase and Camentioning

confidence: 99%

“…One unit of SOD was defined as the amount of enzyme needed to exhibit 50% dismutation of the superoxide radicals. 23 SOD concentration was expressed as U/mg protein.…”

Section: Measurement Of Malondialdehyde Superoxide Dismutase and Camentioning

confidence: 99%

Neuroprotective Effect of Curcumin in an Experimental Rat Model of Subarachnoid Hemorrhage

Kuo

Wen

et al. 2011

Anesthesiology

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“…Reactive astrogliosisis is typically characterized by astrocyte proliferation and hypertrophy (MacFabe et al, 2008). Decreased or increased density of glial cells has been shown in many fundamental works on animal models that were aimed on research of irradiation consequences.…”

Section: Introductionmentioning

confidence: 99%

Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

Alexandrovna¹,

Andreevich²,

Maratovna³

et al. 2014

American Journal of Neuroscience

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Radiation-induced cognitive dysfunction is a serious complication of radiation therapy. In humans, numerous cases of radiation damage have been recorded after irradiation for therapeutic purposes. The degree of cognitive dysfunctions and its dependence on biological effective doses should be tested in animal preclinical models to minimize radiation side effects. Fractionated whole brain irradiation was performed according to the following schemes: 18 Fractions of 2 Gy each (36Gy/18), 9 fractions of 4 Gy each (36Gy/9), 6 fractions of 6 Gy each (36Gy/6), with the biological effective dose 36Gy, 50.4Gy, 64.8Gy correspondingly. Cognitive impairment was detected by a Novel object recognition test in 36Gy/18 and 36Gy/9 groups. Recognition memory impairment was increased in inverse proportion to the biological effective dose. In the 36Gy/6 group, increased anxiety and decreased research activity in Spontaneous alternation test in Y-shaped maze were observed. Reactions of astroglia and vascular reactions were evaluated using qPCR of Glial Fibrillar Acid Protein (GFAP) and Vascular Endothelial Growth Factor (VEGF) genes and immunohistochemical analyses of these proteins. Despite of various biological effective doses (and its subsequent increasing in chosen 3 fractionation schemes) a dose-depended effect in the expression of VEGF in the prefrontal cortex and GFAP in hippocampus and in cognitive impairment was not observed. Cognitive impairment after fractionated whole brain irradiation was clearly seen in our research. The described pathologic changes in healthy brain play an important role in development of radiation-induced cognitive dysfunction. Therefore, applicability of radiobiological models for evaluation of effects of fractionated whole brain irradiation on cognitive dysfunction put in question in our study. So we can suggest that it needs essential more researches about the choice an optimal fractionated scheme to minimize side effects of ionizing radiation.

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A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

Cited by 97 publications

References 140 publications

Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism

Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism

Neuroprotective Effect of Curcumin in an Experimental Rat Model of Subarachnoid Hemorrhage

Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

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