SIRT1 Regulates Dendritic Development in Hippocampal Neurons

Codocedo, Juan Francisco; Allard, Claudio; Godoy, Juan A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.

doi:10.1371/journal.pone.0047073

Cited by 66 publications

(45 citation statements)

References 50 publications

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“…Codocedo et al later proved that SIRT1 overexpression was sufficient to change dendritic morphogenesis in the hippocampi and offer certain resistance against the cytotoxic damage induced by Aβ and avoid neuritic dystrophy [37]. Hence, the causal relationship between miR-34c and changes in dendritic spines in our study can be verified.…”

Section: Discussionsupporting

confidence: 71%

miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline

Kao

Wang

Tsai

2018

IJMS

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Microribonucleic acids (miRNAs) play a pivotal role in numerous aspects of the nervous system and are increasingly recognized as key regulators in neurodegenerative diseases. This study hypothesized that miR-34c, a miRNA expressed in mammalian hippocampi whose expression level can alter the hippocampal dendritic spine density, could induce memory impairment akin to that of patients with Alzheimer’s disease (AD) in mice. In this study, we showed that miR-34c overexpression in hippocampal neurons negatively regulated dendritic length and spine density. Hippocampal neurons transfected with miR-34c had shorter dendrites on average and fewer filopodia and spines than those not transfected with miR-34c (control mice). Because dendrites and synapses are key sites for signal transduction and fundamental structures for memory formation and storage, disrupted dendrites can contribute to AD. Therefore, we supposed that miR-34c, through its effects on dendritic spine density, influences synaptic plasticity and plays a key role in AD pathogenesis.

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Section: Discussionsupporting

confidence: 71%

miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline

Kao

Wang

Tsai

2018

IJMS

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“…Recent reports indicated that SIRT1 protein level and deacetylase activity decreased with age [36]. Upregulation of SIRT1 promoted dendritic development and neurogenesis [37], enhanced hippocampal neuronal synaptic plasticity, facilitated learning and memory and inhibited neurodegeneration [38]. However, SIRT1 expression varied in different regions of the brain and might be regulated by resveratrol in a tissue- and region-specific way [39].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

Wang

Yang

et al. 2018

Behavioural Brain Research

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Mesenchymal stem cell transplantation is a promising therapeutic approach for Alzheimer’s disease (AD). However, poor engraftment and limited survival rates are major obstacles for its clinical application. Resveratrol, an activator of silent information regulator 2, homolog 1 (SIRT1), regulates cell destiny and is beneficial for neurodegenerative disorders. The present study is designed to explore whether resveratrol regulates the fate of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and whether hUC-MSCs combined with resveratrol would be efficacious in the treatment of neurodegeneration in a mouse model of AD through SIRT1 signaling. Herein, we report that resveratrol facilitates hUC-MSCs engraftment in the hippocampus of AD mice and resveratrol enhances the therapeutic effects of hUC-MSCs in this model as demonstrated by improved learning and memory in the Morris water maze, enhanced neurogenesis and alleviated neural apoptosis in the hippocampus of the AD mice. Moreover, hUC-MSCs and resveratrol jointly regulate expression of hippocampal SIRT1, PCNA, p53, ac-p53, p21, and p16. These data strongly suggests that hUC-MSCs transplantation combined with resveratrol may be an effective therapy for AD.

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“…Secondly, there are reports on the role of SIRTs in an altered HPA axis activity [40] . The HPA stress response may be related to the risk of SB in BD [41,42] , with studies showing elevated levels of corticotropin-releasing factor and corticotropin-releasing hormone in the cerebrospinal fluid of suicidal individuals [43] , reduced plasma adrenocorticotropin and cortisol responsiveness and fewer binding sites for corticotropin-releasing hormone in the frontal cortex [44] .…”

Section: Discussionmentioning

confidence: 99%

Association between Sirtuin 1 Gene rs10997870 Polymorphism and Suicide Behaviors in Bipolar Disorder

et al. 2016

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Background/Aims: Suicidal behavior (SB) in bipolar disorder (BD) is a complex multifactorial event resulting from an interaction of genetic, neurobiological and psychosocial factors. Recent studies identified new possible mechanisms, suggesting a role for sirtuins (SIRTs 1-7), a family of nicotinamide adenine dinucleotide-dependent enzymes with a multifaceted role in the central nervous system. The aims of the present study were: (1) to investigate the effects of the rs10997870 SIRT1 gene variant on SB in BD; (2) to explore the effects of the same gene variant on specific depressive symptoms at the severest episode. Methods: One hundred and eighty DSM-IV bipolar outpatients were enrolled in a naturalistic cohort study. The rs10997870 polymorphism within the SIRT1 gene was analyzed. Results: An association between the GG genotype and SB was detected (lifetime: p = 0.015). Compared to other genotypes, GG carriers presented more frequently psychomotor agitation (p = 0.009) and a higher Hamilton Depression Rating Scale total score (p = 0.014) at the severest depressive episode. SB and psychomotor agitation were found to be associated with GG carriers and G allele in a multivariate analysis as well. Conclusion: Our findings suggest a role of the rs10997870 SIRT1 gene variant in SB amongst BD patients and its association with specific depressive symptoms. Despite a number of limitations of this exploratory study, our results may provide new insight into the mechanisms underlying SB in BD.

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SIRT1 Regulates Dendritic Development in Hippocampal Neurons

Cited by 66 publications

References 50 publications

miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline

miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

Association between Sirtuin 1 Gene rs10997870 Polymorphism and Suicide Behaviors in Bipolar Disorder

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