Resveratrol, a SIRT1 Activator, Ameliorates MK-801-Induced Cognitive and Motor Impairments in a Neonatal Rat Model of Schizophrenia

Niu, Juan; Cao, Yuquan; Ji, Yong-juan

doi:10.3389/fpsyt.2020.00716

Cited by 29 publications

(13 citation statements)

References 47 publications

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“…Female animals were included in the MAM model along with the males as there are very few reports on MAM models of schizophrenia using female animals [45,46]. Although the doses of 0.5 mg/Kg and 1.0 mg/Kg of MK-801 were used previously in separate studies, our study involves detailed comparative analysis of behaviour upon administration of these doses [29][30][31][32][47][48][49]. In our treatment regime, the washout period of 5 days ensures that the drug per se won't interfere with the behavior and hence the observed behavioral changes could be arising from the drug-induced changes in the brain tissue (Figure 4 and 5).…”

Section: Discussionmentioning

confidence: 99%

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Novel microRNAs targeting NMDA receptor subunits in animal models of schizophrenia

Gunasekaran

Jacob

Omkumar

2021

Preprint

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N-methyl-D-aspartate receptors (NMDAR) are downregulated in schizophrenia possibly through microRNAs (miRNAs) that are differentially expressed in this condition. We screened the miRNAs that are altered in schizophrenia against the targets, Grin2A and Grin2B subunits of NMDAR using bioinformatic tools. Among the predicted miRNAs some interacted with the 3`UTR sequences of Grin2A (miR-296, miR-148b, miR-129-2, miR-137) and Grin2B (miR-296, miR-148b, miR-129-2, miR-223) in dual luciferase assays. This was supported by downregulation of the GluN2B protein in primary hippocampal neurons upon overexpressing Grin2B targeting miRNAs. In two models of schizophrenia- pharmacological MK-801 model and neurodevelopmental methylazoxymethanol acetate (MAM) model which showed cognitive deficits - protein levels of GluN2A and GluN2B were downregulated but their transcript levels were upregulated. MiR-296-3p, miR-148b-5p and miR-137 levels showed upregulation in both models which could have interacted with Grin2A/Grin2B transcripts resulting in translational arrest. In MAM model, reciprocal changes in the expression of the 3p and 5p forms of miR-148b and miR-137 were observed. Expression of neuregulin 1 (NRG1), BDNF and CaMKIIα, genes implicated in schizophrenia, were also altered in these models. This is the first report of downregulation of GluN2A and GluN2B by miR-296, miR-148b and miR-129-2. Mining miRNAs regulating NMDA receptors might give insights into the pathophysiology of this disorder, providing avenues in therapeutics.

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Section: Discussionmentioning

confidence: 99%

“…MK-801 is a non-competitive NMDAR channel blocker. It was intraperitoneally administered in two different doses -0.5 mg/Kg and 1.0 mg/Kg for five days based on previous reports [30][31][32][33]. The resulting blockage of NMDAR is expected to cause alterations in the brain similar to schizophrenia.…”

Section: 41treatment Regimes For the Animal Modelsmentioning

confidence: 99%

Novel microRNAs targeting NMDA receptor subunits in animal models of schizophrenia

Gunasekaran

Jacob

Omkumar

2021

Preprint

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“…PLSs may also have other accompanying symptoms, such as cognition impairment and emotional disorder (e.g., mania and depression) ( 7 , 8 ). Schizophrenia can occur at different stages of life course, while the risk varies across different age groups ( 9 ). Reports have shown that the prevalence of schizophrenia changes with age in an inverted U-shape, with the highest value at around 40 years of age.…”

Section: Introductionmentioning

confidence: 99%

Associations of Caregiving Knowledge and Skills With Caregiver Burden, Psychological Well-Being, and Coping Styles Among Primary Family Caregivers of People Living With Schizophrenia in China

Zhou

Wang

Feng³

et al. 2021

Front. Psychiatry

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Background: There is a lack of clarity regarding the correlation of caregiving knowledge and skills with caregiving experiences of people living with schizophrenia (PLSs). To address this gap, this comprehensive study examines the relationships of caregiving knowledge and skills to the primary family caregiver's experiences of burden, psychological well-being (stress, anxiety, depression, caregiving rewarding feelings), and coping styles in China.Methods: A total of 395 primary family caregivers of PLSs were enrolled in a cross-sectional study between May 2019 and September 2019. Each family caregiver was independently assessed on caregiving knowledge and skills, caregiver burden, and psychological well-being, as well as coping styles.Results: A higher level of caregiving knowledge and skills was positively correlated with less stress (b = −0.48, P < 0.001), anxiety (b = −0.23, P = 0.029), depression (b = −0.29, P = 0.013), and more caregiving rewarding feelings (b = 0.54, P < 0.001). Also, caregivers with more knowledge and skills were more inclined to adopt positive coping strategies (b = 0.44, P < 0.001). Despite these differences, caregivers with different levels of caregiving knowledge and skills reported comparable caregiver burden (b = 0.11, P = 0.705) and the use of a passive coping style (b = 0.10, P = 0.169).Conclusion: Caregiving knowledge and skills are a reliable predictor of psychological well-being and active coping among the primary family caregivers of PLSs. These findings inform the development of psychoeducational interventions to support family caregivers of PLSs.

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“…Each mouse was tested for three trials with an interval of 30 min. The time spent on the rotating rod was used for evaluation of the motor coordination and balance 59 .…”

Section: Methodsmentioning

confidence: 99%

A novel lncRNA Discn fine-tunes replication protein A (RPA) availability to promote genomic stability

Wang

Zhou

et al. 2021

Nat Commun

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RPA is a master regulator of DNA metabolism and RPA availability acts as a rate-limiting factor. While numerous studies focused on the post-translational regulations of RPA for its functions, little is known regarding how RPA availability is controlled. Here we identify a novel lncRNA Discn as the guardian of RPA availability in stem cells. Discn is induced upon genotoxic stress and binds to neucleolin (NCL) in the nucleolus. This prevents NCL from translocation into nucleoplasm and avoids undesirable NCL-mediated RPA sequestration. Thus, Discn-NCL-RPA pathway preserves a sufficient RPA pool for DNA replication stress response and repair. Discn loss causes massive genome instability in mouse embryonic stem cells and neural stem/progenigor cells. Mice depleted of Discn display newborn death and brain dysfunctions due to DNA damage accumulation and associated inflammatory reactions. Our findings uncover a key regulator of DNA metabolism and provide new clue to understand the chemoresistance in cancer treatment.

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Resveratrol, a SIRT1 Activator, Ameliorates MK-801-Induced Cognitive and Motor Impairments in a Neonatal Rat Model of Schizophrenia

Cited by 29 publications

References 47 publications

Novel microRNAs targeting NMDA receptor subunits in animal models of schizophrenia

Novel microRNAs targeting NMDA receptor subunits in animal models of schizophrenia

Associations of Caregiving Knowledge and Skills With Caregiver Burden, Psychological Well-Being, and Coping Styles Among Primary Family Caregivers of People Living With Schizophrenia in China

A novel lncRNA Discn fine-tunes replication protein A (RPA) availability to promote genomic stability

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