Erythropoietin shows gender dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide induced rat model of autism

Solmaz, Volkan; Erdoğan, Mehmet; Alnak, Alper; Meral, Ayfer; Erbaş, Oytun

doi:10.1016/j.npep.2020.102073

Cited by 13 publications

(11 citation statements)

References 42 publications

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“…Lipopolysaccharide (LPS), a complex of lipids and polysaccharides, is the main component of the cell walls of gram-negative bacteria. LPS injection in pregnant rats can cause ASD symptoms in offspring and is thus currently a commonly used method to induce an immune ASD model in rats ( 72 ). However, LPS can induce the expression of iNOS in glial cells ( 73 ), thereby causing the production of large amounts of NO.…”

Section: The No Signaling Pathway and Asdmentioning

confidence: 99%

A Probable Way Vitamin D Affects Autism Spectrum Disorder: The Nitric Oxide Signaling Pathway

Wang

Dong

et al. 2022

Front. Psychiatry

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Vitamin D (VD) deficiency during pregnancy and early brain development is an important environmental risk factor for autism spectrum disorder (ASD). Its specific mechanism of action is still unclear. However, one study on the correlation between metabolomics and VD levels in children with ASD has found that the whole-blood arginine (Arg) levels of children with ASD are significantly negatively correlated with serum VD levels, suggesting that the effect of VD on ASD may be related to the signaling pathway involving Arg. Arg is a precursor of nitric oxide (NO), and changes in its levels most directly affect NO levels and signal transduction pathways. NO, a biologically active free radical, is both a neurotransmitter and a neuromodulator in the central nervous system and is related to the pathogeneses of various neurological diseases. The NO signaling pathway is not only affected by VD levels but also closely related to ASD through a series of mechanisms, such as neurotransmitter imbalance, immune disorders, and oxidative stress. Therefore, the effect of VD on ASD may be achieved via regulation of the NO signaling pathway. The current review discusses the relationship among VD, NO, and ASD as suggested by a large body of evidence in the literature in an effort to provide clues for researchers on the pathogenesis of ASD and the mechanism of VD's impact on ASD.

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Section: The No Signaling Pathway and Asdmentioning

confidence: 99%

A Probable Way Vitamin D Affects Autism Spectrum Disorder: The Nitric Oxide Signaling Pathway

Wang

Dong

et al. 2022

Front. Psychiatry

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“…The beneficial effects of EPO on the social behaviors and learning/memory deficits in the lipopolysaccharide (LPS)-induced adult rat model of autism have been shown by Solmaz et al (2020) They indicated that a systemic and long-term (45 days) administration of EPO in adult rats improves autistic-like behaviors (Solmaz et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

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

Ranjbar

Darvishzadeh-Mahani

et al. 2022

Developmental Psychobiology

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In this study, based on the excitatory/inhibitory imbalance theory of autism, the time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in adjustment GABA switch, and brain permeability to erythropoietin (EPO), the effects of postnatal -EPO and-nano-erythropoietin (NEPO) have been evaluated in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism at gestational day (GD) 12.5 (600 mg/kg). Male offsprings were injected with EPO and NEPO in a clinically proper postnatal dosing regimen on postnatal days (PND) 1-5, and autistic-like behaviors were tested at the end of the first month. Then animals were sacrificed, and neuron morphology and KCC2 expression were examined by Nissl staining and Western blot. According to our findings, high-dose NEPO improved autism-associated phenotypes. Neuroprotective effects of EPO and NEPO have been shown in the hippocampus. Postnatal NEPO treatment reversed KCC2 expression abnormalities induced by prenatal VPA. Our results might support the role of KCC2 in ASD and the excitatory/inhibitory imbalance hypothesis. We suggested Nano-erythropoietin and other KCC2 interventions as a new approach to the early treatment and prevention of autism.

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“…An imaging system (Image-Pro Express 1.4.5, Media Cybernetics, Inc. USA) was used for the assessments. 8 , 33 …”

Section: Methodsmentioning

confidence: 99%

“…A microplate reader was used for the measurement of the Absorbances (MultiscanGo, Thermo Fisher Scientific Laboratory Equipment, NH, USA). 33 …”

Section: Methodsmentioning

confidence: 99%

Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study

Doğan¹,

Albayrak²,

Erbas³

2023

ALPHA PSYCHIATRY

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Objective: Autism spectrum disorder is a neurodevelopmental disease in which impaired social behaviors, impaired sociality, and restricted and repetitive behaviors are seen. Bumetanide is a loop diuretic that inhibits Na + –K + –2Cl − cotransporter 1 and it is currently used in clinical phase studies in patients with autism spectrum disorder. In present research, it is purposed to demonstrate the beneficial effects of torasemide which is another Na + –K + –2Cl − cotransporter 1 inhibitor on an experimental autism model induced with propionic acid by providing imaging and brain tissue investigations. Methods: Male Wistar rats were used in the present study (n = 30). Propionic acid of 250 mg/kg/day was administrated intraperitoneally in rats to induce autism for 5 days. Three groups were created for present study as follows: group 1, normal control (n = 10); group 2, propionic acid and saline given group (n = 10); group 3, propionic acid + tora-semide-administrated group (n = 10). Results: Torasemide group scored higher on behavioral tests compared to saline group. The brain levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-2, interleukin-17, and Nuclear Factor kappa B (NF-κB), Glial fibrillary acidic protein (GFAP) were remarkably higher in propionic acid + saline group. In histopathology assessments, torasemide group had higher neuronal count of Cornu Ammonis 1, neuronal count of Cornu Ammonis 2 in hippocampus, and Purkinje cells in cerebellum. GFAP immunostaining index (Cornu Ammonis 1) and cerebellum were lower in torasemide group. Magnetic resonance spectroscopy revealed that mean lactate value was higher in propionic acid + saline group compared to torasemide group. Conclusion: Our experimental results showed that torasemide might enhance gamma-aminobutyric acid activity. Torasemide can be considered another promising Na + –K + –2Cl − cotransporter 1 inhibitor in the treatment of autism with a longer half-life and less side effects after further studies.

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Erythropoietin shows gender dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide induced rat model of autism

Cited by 13 publications

References 42 publications

A Probable Way Vitamin D Affects Autism Spectrum Disorder: The Nitric Oxide Signaling Pathway

A Probable Way Vitamin D Affects Autism Spectrum Disorder: The Nitric Oxide Signaling Pathway

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

Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study

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