Selective modulator of peroxisome proliferator-activated receptor-α protects propionic acid induced autism-like phenotypes in rats

Mirza, Roohi; Sharma, Bhupesh

doi:10.1016/j.lfs.2018.10.045

Cited by 44 publications

(50 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 92%

“…Interesting EM observation was the increased number of peroxisomes and endosomes in the CA1 area of the PPA‐treated brain. Such an ultrastructural feature usually indicates to the increased endocytic activity and the activation of reactive oxygen species detoxification system (Mirza & Sharma, ; Patak, Zhang‐James, & Faraone, ; Von Bartheld & Altick, ). The data are reminiscent with our previous biochemical results, according which chronic ICV administration of PPA provokes the aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction, coupling capacity and neuroinflammation, all of which may be associated with ASD pathogenesis (MacFabe et al, ; Thomas et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The data are reminiscent with our previous biochemical results, according which chronic ICV administration of PPA provokes the aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction, coupling capacity and neuroinflammation, all of which may be associated with ASD pathogenesis (MacFabe et al, ; Thomas et al, ). Of note, a recent study found a selective modulator of peroxisome proliferator‐activated receptor protects PPA‐induced autism‐like phenotype in rats (Mirza & Sharma, ). Interestingly, peroxisomes and endosomes were rare in the amygdala of rats treated with PPA treated in the same manner to this present study (Lobzhanidze et al, ).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…The social interaction was investigated using three‐chamber social interaction testing apparatus (57 cm x 36 cm x 30 cm) as previously described (Mirza and Sharma, 2018). Briefly, the testing method was consisted three sessions.…”

Section: Methodsmentioning

confidence: 99%

“…The series of rat entries in three different arms in succession were noted as an alteration to calculate the number of spontaneous alternations. The reduction in the percentage of spontaneous alterations of rat was index of the repetitive behavior the duration of test was 8 min (Markram et al, 2008; Mirza and Sharma, 2018).…”

Section: Methodsmentioning

confidence: 99%

Beneficial effects of pioglitazone, a selective peroxisome proliferator‐activated receptor‐γ agonist in prenatal valproic acid‐induced behavioral and biochemical autistic like features in Wistar rats

Mirza

Sharma

2019

Intl J of Devlp Neuroscience

Self Cite

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosis by two main behavioral phenotypes i.e. social‐communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. Valproic acid (VPA), a teratogen is known to induce characteristic features related to ASD in rodents. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR‐γ, pioglitazone in prenatal VPA induced experimental ASD symptomatology in Wistar rats. The prenatal administration of VPA has induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, prenatal VPA‐treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species, and decreased in reduced glutathione level) and inflammation (increased in interleukin‐6, tumor necrosis factor‐alpha and decreased in interleukin‐10) in the cerebellum, brainstem and prefrontal cortex. Treatment with pioglitazone significantly attenuated the prenatal VPA‐induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the prenatal VPA‐induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, it may be concluded that pioglitazone may provide neurobehavioral and biochemical benefits in prenatal VPA‐induced autistic phenotypes in rats.

show abstract

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress

Luhach

Kulkarni²,

Singh

et al. 2021

Autism Research

Self Cite

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal-valproic acid (pre-VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-α) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre-VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre-VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB/CREB, IL-10, and GSH along with significant decrease in TNF-α, IL-6, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre-VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD. Lay SummaryASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens-up a new line of enquiry for ASD treatment.

show abstract

Selective modulator of peroxisome proliferator-activated receptor-α protects propionic acid induced autism-like phenotypes in rats

Cited by 44 publications

References 58 publications

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

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

Beneficial effects of pioglitazone, a selective peroxisome proliferator‐activated receptor‐γ agonist in prenatal valproic acid‐induced behavioral and biochemical autistic like features in Wistar rats

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress

Contact Info

Product

Resources

About