Anethole via increase in the gene expression of PI3K/AKT/mTOR mitigates the autistic-like behaviors induced by maternal separation stress in mice

Yadollahi-Farsani, Yasaman; Vanani, Vahid Reisi; Lorigooini, Zahra; Farahzad, Anahita; Amini-Khoei, Hossein

doi:10.1016/j.ibneur.2023.11.009

Cited by 6 publications

(3 citation statements)

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“…injections. The doses of drug administrations were chosen based on a pilot and previous studies 18 , 24 , 25 .…”

Section: Methodsmentioning

confidence: 99%

Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance

Rostami-Faradonbeh,

Amini-Khoei,

Zarean

et al. 2024

Sci Rep

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The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus.

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“…injections. The doses of drug administrations were chosen based on a pilot and previous studies 18 , 24 , 25 .…”

Section: Methodsmentioning

confidence: 99%

Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance

Rostami-Faradonbeh,

Amini-Khoei,

Zarean

et al. 2024

Sci Rep

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“…Ample evidence has been demonstrated that MS could lead to neurotransmission, neuroendocrine, and neurostructural alterations in the central nervous system (CNS) ( Gildawie et al, 2021 ). It has been well-determined that MS via neurotransmission and neurostructural modifications in the brain provoked autistic-like behaviors in rodents, indicating that the MS paradigm could be considered as an experimental model of Autism in rodents ( Mansouri et al, 2021 ; Farzan et al, 2023 ; Khaledi et al, 2023 ; Moghaddam et al, 2023 ; Yadollahi-Farsani et al, 2023 ). MS, with its abovementioned changes in the hippocampus, causes mood-behavioral disorders ( Arabi et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Umbelliprenin via increase in the MECP2 and attenuation of oxidative stress mitigates the autistic-like behaviors in mouse model of maternal separation stress

Karimi,

Ghahfarroki,

Lorigooini

et al. 2024

Front. Pharmacol.

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Introduction: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition. Maternal separation (MS) stress is an early-life stress factor associated with behaviors resembling Autism. Both MECP2 and oxidative stress are implicated in the pathophysiology of Autism. Umbelliprenin (UMB) is a coumarin compound with various pharmacological properties. Our study aimed to investigate the potential effects of UMB in mitigating autistic-like behaviors in a mouse model subjected to MS stress, focusing on probable alterations in MECP2 gene expression in the hippocampus.Methods: MS paradigm was performed, and mice were treated with saline or UMB. Behavioral tests consisting of the three-chamber test (evaluating social interaction), shuttle box (assessing passive avoidance memory), elevated plus-maze (measuring anxiety-like behaviors), and marble-burying test (evaluating repetitive behaviors) were conducted. Gene expression of MECP2 and measurements of total antioxidant capacity (TAC), nitrite level, and malondialdehyde (MDA) level were assessed in the hippocampus.Results: The findings demonstrated that MS-induced behaviors resembling Autism, accompanied by decreased MECP2 gene expression, elevated nitrite, MDA levels, and reduced TAC in the hippocampus. UMB mitigated these autistic-like behaviors induced by MS and attenuated the adverse effects of MS on oxidative stress and MECP2 gene expression in the hippocampus.Conclusion: In conclusion, UMB likely attenuated autistic-like behaviors caused by MS stress, probably, through the reduction of oxidative stress and an increase in MECP2 gene expression.

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“…Studies have shown that early life stresses (ELS) such as maternal separation (MS) play an important role in the development of neuropsychiatric disorders (Kambali et al, 2019; Rao et al, 2010). There is growing evidence that MS is associated with the development of ASD (Farzan et al, 2023; Khaledi et al, 2023; Makris et al, 2023; Reisi‐Vanani et al, 2023; Yadollahi‐Farsani et al, 2024). It has been demonstrated that MS is associated with disturbance in the gut–brain axis (Amini‐Khoei et al, 2019; O'Mahony et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Gut—brain barrier dysfunction bridge autistic‐like behavior in mouse model of maternal separation stress: A behavioral, histopathological, and molecular study

Rowshan,

Anjomshoa,

Farahzad

et al. 2024

Intl J of Devlp Neuroscience

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Autism spectrum disorder (ASD) is a fast‐growing neurodevelopmental disorder throughout the world. Experiencing early life stresses (ELS) like maternal separation (MS) is associated with autistic‐like behaviors. It has been proposed that disturbance in the gut–brain axis‐mediated psychiatric disorders following MS. The role of disruption in the integrity of gut–brain barrier in ASD remains unclear. Addressing this knowledge gap, in this study we aimed to investigate role of the gut–brain barrier integrity in mediating autistic‐like behaviors in mouse models of MS stress. To do this, mice neonates are separated daily from their mothers from postnatal day (PND) 2 to PND 14 for 3 hours. During PND58–60, behavioral tests related to autistic‐like behaviors including three‐chamber sociability, shuttle box, and resident‐intruder tests were performed. Then, prefrontal cortex (PFC), hippocampus, and colon samples were dissected out for histopathological and molecular evaluations. Results showed that MS is associated with impaired sociability and social preference indexes, aggressive behaviors, and impaired passive avoidance memory. The gene expression of CLDN1 decreased in the colon, and the gene expression of CLDN5, CLDN12, and MMP9 increased in the PFC of the MS mice. MS is associated with decrease in the diameter of CA1 and CA3 areas of the hippocampus. In addition, MS led to histopathological changes in the colon. We concluded that, probably, disturbance in the gut–brain barrier integrities mediated the autistic‐like behavior in MS stress in mice.

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Anethole via increase in the gene expression of PI3K/AKT/mTOR mitigates the autistic-like behaviors induced by maternal separation stress in mice

Cited by 6 publications

References 64 publications

Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance

Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance

Umbelliprenin via increase in the MECP2 and attenuation of oxidative stress mitigates the autistic-like behaviors in mouse model of maternal separation stress

Gut—brain barrier dysfunction bridge autistic‐like behavior in mouse model of maternal separation stress: A behavioral, histopathological, and molecular study

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