The effects of postnatal erythropoietin and nano‐erythropoietin on behavioral alterations by mediating K‐Cl co‐transporter 2 in the valproic acid‐induced rat model of autism

Haratizadeh, Sara; Ranjbar, Mehdi; Darvishzadeh-Mahani, Fatemeh; Basiri, Mohsen; Nozari, Masoumeh

doi:10.1002/dev.22353

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…It has also been identified as a neuromodulating agent able to regulate mitochondrial function in the hippocampus and affect cognitive outcomes in an animal model, and that EP300 , a transcriptional regulator of EPO, appears on a “high-confidence” list of genes associated with neurodevelopmental disorders [ 41 – 44 ]. A recent study highlighted a potential role of erythropoietin in improving autistic-like behaviors in rats with the valproate-induced model of autism, associated with the restored expression of K-Cl cotransporter encoded by Slc12a5 [ 45 ]. Another study suggested that an association may exist between high umbilical cord serum EPO levels and an increased risk for severe neurocognitive morbidity in early childhood even after adjusting for the gestational age [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology

Shchelochkov,

Farmer,

Chlebowski

et al. 2024

Mol Psychiatry

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Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters. Twenty (61%) participants received an ID diagnosis, and 12 of the 31 (39%) who were fully evaluated received the diagnosis of ASD. A diagnosis of ID, lower full-scale IQ (sample mean = 65 ± 26), and lower adaptive behavior composite scores (sample mean = 67 ± 23) were associated with several biomarkers. Higher concentrations of plasma propionylcarnitine, plasma total 2-methylcitrate, serum erythropoietin, and mitochondrial biomarkers plasma FGF21 and GDF15 were associated with a more severe ID profile. Reduced 1-13C-propionate oxidative capacity and decreased levels of plasma and urinary glutamine were also associated with a more severe ID profile. Only two parameters, increased serum erythropoietin and decreased plasma glutamine, were associated with ASD. Plasma glycine, one of the defining features of PA, was not meaningfully associated with either ID or ASD. Thus, while both ID and ASD were commonly observed in our PA cohort, only ID was robustly associated with metabolic parameters. Our results suggest that disease severity and associated mitochondrial dysfunction may play a role in CNS complications of PA and identify potential biomarkers and candidate surrogate endpoints.

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Section: Discussionmentioning

confidence: 99%

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology

Shchelochkov,

Farmer,

Chlebowski

et al. 2024

Mol Psychiatry

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“…The SI and SPI scores were between -1 and 1; the values closer to 1 indicate that the animal is more social, while the negative scores show that the animal has no sociability or social preference. 17 …”

Section: Methodsmentioning

confidence: 99%

Effects of Nicotine Administration in an Enriched Environment on the Behavior of Male MK-801-Exposed Rats

Salmani,

Darvishzadeh Mahani,

Parvan

et al. 2023

Addict Health

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Background: Smoking is more common in patients with schizophrenia than in healthy populations. Some controversial hypotheses connect the disease with the high prevalence of smoking. Moreover, environmental factors affect the severity of the positive and negative symptoms of schizophrenia. The current study aimed to assess the effect of enriched environment (EE) and nicotine on the MK-801 animal model of schizophrenia. Methods: Male Wistar rat pups randomly received saline or MK-801 (dose:1 mg/kg) for five days from the sixth postnatal day (P) until the tenth. The pups were placed in EE or standard cages (SCs) after weaning (P21). Morris water maze (MWM) was used to assess spatial learning and memory. The rats received 0.6 mg/kg nicotine twice for three days at the end of the second month and were examined in an open-field box and three-chamber social interaction test. Findings: MK-801 rats’ behaviors were the same as those of the saline rats when they were exposed to nicotine. No positive effects of EE were observed when the animals were exposed to nicotine. Conclusion: The results suggested that nicotine decreased schizophrenia-like symptoms and covered the positive effects of EE.

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“…It appears that genetic (De Rubeis et al , 2014; Hansen et al , 2015) and environmental (Chiarotti and Venerosi, 2020) factors influence the pathogenesis of ASD. Researchers have found that the maternal use of valproic acid (VPA) during pregnancy increases the risk of autism in humans (Ornoy, 2009) and rodents (Sabzalizadeh et al 2022; Haratizadeh et al 2023).…”

Section: Introductionmentioning

confidence: 99%

Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist

Taheri

Esmaeilpour

Sepehri

et al. 2023

Behavioural Pharmacology

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Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behavior. Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R). In this study, the effects of ciproxifan (CPX) (1 and 3 mg/kg, intraperitoneally) on cognitive impairments in rat pups exposed to valproic acid (VPA) (600 mg/kg, intraperitoneally) wereexamined on postnatal day 48–50 (PND 48–50) using marble-burying task (MBT), open field, novel object recognition (NOR), and Passive avoidance tasks. Famotidine (FAM) (10, 20, and 40 mg/kg, intraperitoneally) was also used to determine whether histaminergic neurotransmission exerts its procognitive effects via H2 receptors (H2Rs). Furthermore, a histological investigation was conducted to assess the degree of degeneration of hippocampal neurons. The results revealed that repetitive behaviors increased in VPA-exposed rat offspring in the MBT. In addition, VPA-exposed rat offspring exhibited more anxiety-like behaviors in the open field than saline-treated rats. It was found that VPA-exposed rat offspring showed memory deficits in NOR and Passive avoidance tasks. Our results indicated that 3 mg/kg CPX improved cognitive impairments induced by VPA, while 20 mg/kg FAM attenuated them. We concluded that 3 mg/kg CPX improved VPA-induced cognitive impairments through H3Rs. The histological assessment showed that the number of CA1 neurons decreased in the VPA-exposed rat offspring compared to the saline-exposed rat offspring, but this decrease was not significant. The histological assessment also revealed no significant differences in CA1 neurons in VPA-exposed rat offspring compared to saline-exposed rat offspring. However, CPX3 increased the number of CA1 neurons in the VPA + CPX3 group compared to the VPA + Saline group, but this increase was not significant. This study showed that rats prenatally exposed to VPA exhibit cognitive impairments in the MBT, open field, NOR, and Passive avoidance tests, which are ameliorated by CPX treatment on PND 48–50. In addition, morphological investigations showed that VPA treatment did not lead to neuronal degeneration in the CA1 subfield of the hippocampus in rat pups.

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The effects of postnatal erythropoietin and nano‐erythropoietin on behavioral alterations by mediating K‐Cl co‐transporter 2 in the valproic acid‐induced rat model of autism

Cited by 5 publications

References 38 publications

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology

Effects of Nicotine Administration in an Enriched Environment on the Behavior of Male MK-801-Exposed Rats

Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist

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