Photobiomodulation Attenuated Cognitive Dysfunction and Neuroinflammation in a Prenatal Valproic Acid-Induced Autism Spectrum Disorder Mouse Model

Kim, Ui-Jin; Hong, Namgue; Ahn, Jin‐Chul

doi:10.3390/ijms232416099

Cited by 12 publications

(5 citation statements)

References 65 publications

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“…This is in line with a previous study showing that GOS decreased elevated CD68 mRNA levels in the hippocampus after abdominal surgery, which resulted in an improvement of cognitive dysfunction and neuroinflammation [73]. In contrast, no differences were observed in microglial activation in the mPFC, consistent with other studies using the VPA mouse model [27,74], suggesting a brain region dependency. Overall, the GOS/FOS diet demonstrated an immunomodulatory effect in the brain in the presence of neuroinflammation, mitigating the detrimental effects of in utero VPA exposure on social behavior and spatial memory.…”

Section: Discussionsupporting

confidence: 93%

Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder

Prince,

Peralta Marzal,

Markidi

et al. 2024

Acta Pharmacol Sin

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Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.

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Section: Discussionsupporting

confidence: 93%

Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder

Prince,

Peralta Marzal,

Markidi

et al. 2024

Acta Pharmacol Sin

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“…Our study did not reveal any statistical disparities between VPA-exposed rats and the control group in terms of spatial learning and memory, aligning with the findings of certain researchers ( Markram et al, 2008 ; Bambini-Junior et al, 2011 ). However, contrasting studies have reported impaired spatial learning and memory in VPA-exposed rats ( Hou et al, 2018 ; Rajizadeh et al, 2019 ; Kim et al, 2022 ).…”

Section: Discussionmentioning

confidence: 90%

Effects of hyperbaric oxygen therapy on autistic behaviors and GRIN2B gene expression in valproic acid-exposed rats

Mohtaj Khorassani,

Moghimi,

Khakzad

et al. 2024

Front. Neurosci.

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IntroductionAutism is a complex neurodevelopmental condition characterized by deficits in social interaction, communication, and restricted repetitive behaviors. Hyperbaric oxygen therapy (HBOT) has emerged as a potential treatment for autism, although its effects on behavior and gene expression are not well understood. The GRIN2B gene, known for its involvement in encoding a glutamate receptor subunit crucial for neuron communication and associated with autism, was a focus of this study.MethodsUsing a rat model induced by prenatal exposure to valproic acid, we examined the impact of HBOT on autism-like behaviors and GRIN2B gene expression. Male Wistar rats were categorized into four groups: control, VPA (valproic acid-exposed), VPA+HBOT [2 atmosphere absolute (ATA)], and VPA+HBOT (2.5 ATA). The rats underwent several behavioral tests to assess social behavior, anxiety, stereotype and exploratory behaviors, and learning. Following the behavioral tests, the HBOT groups received 15 sessions of HBOT at pressures of 2 and 2.5 (ATA), and their behaviors were re-evaluated. Subsequently, real-time PCR was employed to measure GRIN2B gene expression in the frontal lobe.ResultsOur results indicated that HBOT significantly increased social interaction and exploratory behaviors in VPA-exposed rats, alongside elevated GRIN2B gene expression in their frontal lobe.DiscussionOur findings imply that HBOT might have a potential role in ameliorating autism-related behaviors in the VPA rat model of autism through potential modulation of GRIN2B gene expression. However, additional research is essential to fully comprehend the underlying mechanisms and refine the HBOT protocol for optimizing its effectiveness in improving autism-related symptoms.

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“…Also, subcutaneous injection of sodium valproate (200 mg/kg on gestational days 12-17) showed a delayed appearance of surface righting as well as negative geotaxis in mice (Wagner et al, 2006). And single intraperitoneal injection of 600 mg/kg VPA in mice revealed a significant delay in negative geotaxis and surface righting reflexes (Kim et al, 2022). Moreover, we found that pups of VPAtreated mothers did not show any delay in physical milestones acquirement including eye opening and pinnae detachment indicating that prenatally VPA exposure did not affect physical milestones maturation.…”

Section: Discussionmentioning

confidence: 96%

Effect of Antiandrogens on Valproic Acid-Induced Neurodevelopmental Changes in Rats

Farghaly

Bakr

Sayed

et al. 2023

Assiut Veterinary Medical Journal

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Autism spectrum disorders are a neurodevelopmental condition characterized by disturbances in social interaction and communication, as well as repetitive and restricted behaviors. No efficient treatment plans have been found so far. The neurodevelopmental effects of antiandrogens on developmental milestones were examined in rats following a single intraperitoneal injection of adult pregnant female rats with valproic acid (VPA) (600 mg/kg) on gestation day 12.5. Control females were injected with physiological saline at the same time. The offspring of set 1 (which received physiological saline) was divided into 2 groups (groups 1&2) and the offspring of set 2 (which received VPA) were divided into 5 groups (groups 3-7). Thus, the seven groups were organized as follows: Group 1, the control group in which pups did not receive any treatment. Group 2, pups were given sesame oil vehicle. Group 3 pups did not receive any further treatment. Group 4 in which the pups were given sesame oil. Group 5 in which the pups received 1 mg/day testosterone propionate subcutaneously. Group 6 in which the pups received flutamide 1 mg/kg subcutaneously. Group 7 in which the pups received finasteride 50 mg/kg subcutaneously. Our results demonstrated that VPA-induced retardation in sensorimotor reflexes, but did not affect physical landmarks while antiandrogens improved developmental milestones. In conclusion, our finding confirms that androgen contributes partially towards VPA-induced neurodevelopmental insults.

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Photobiomodulation Attenuated Cognitive Dysfunction and Neuroinflammation in a Prenatal Valproic Acid-Induced Autism Spectrum Disorder Mouse Model

Cited by 12 publications

References 65 publications

Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder

Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder

Effects of hyperbaric oxygen therapy on autistic behaviors and GRIN2B gene expression in valproic acid-exposed rats

Effect of Antiandrogens on Valproic Acid-Induced Neurodevelopmental Changes in Rats

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