Running for REST: Physical activity attenuates neuroinflammation in the hippocampus of aged mice

Dallagnol, Karine Mathilde Campestrini; Remor, Aline Pertile; Silva, Rodrigo A. da; Prediger, Rui Daniel; Latini, Alexandra

doi:10.1016/j.bbi.2016.07.159

Cited by 34 publications

(28 citation statements)

References 25 publications

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“…Consistent with our findings, several previous studies identified an interaction of the APOE gene with the APP [25,26], PICALM [24], PSEN1 [27], and PSEN2 [26] genes by stratifying APOE ε4 carrier status. Moreover, evidence has been reported for an association of the REST gene with slow hippocampal loss, brain aging, AD pathology, and protection from oxidative stress and amyloid β-protein toxicity [3,4,5,6]. Furthermore, the REST gene may act not only as a primary repressor for normal neurogenesis but also as an essential protector against neurodegeneration [3,4,5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, evidence has been reported for an association of the REST gene with slow hippocampal loss, brain aging, AD pathology, and protection from oxidative stress and amyloid β-protein toxicity [3,4,5,6]. Furthermore, the REST gene may act not only as a primary repressor for normal neurogenesis but also as an essential protector against neurodegeneration [3,4,5,6]. Additionally, it should be noted that the A allele frequency of REST rs1277306 varies considerably between different ethnic populations, ranging from 42% in the present Taiwanese population to 75.8% in European subjects, 44.7% in Japanese subjects, 85.3% in African American subjects, and 46.1% in Han Chinese subjects as shown in the public data from the 1000 Genomes Project (http://www.1000genomes.org).…”

Section: Discussionmentioning

confidence: 99%

“…The protein encoded by the REST gene has been implicated in the regulation of neuronal differentiation, axonal growth, vesicular transport, ion channels, and synaptic plasticity [2,3]. The REST gene has previously been associated with mild cognitive impairment and Alzheimer disease (AD) [4,5,6]. Lu et al [4] showed that the REST protein was almost undetectable in the nucleus of cortical and hippocampal neurons in aging individuals with mild cognitive impairment or AD.…”

Section: Introductionmentioning

confidence: 99%

“…Lu et al [4] showed that the REST protein was almost undetectable in the nucleus of cortical and hippocampal neurons in aging individuals with mild cognitive impairment or AD. Additionally, the REST protein plays a beneficial role in the aged brain and appears to activate genes involved in AD pathology as well as protect neurons from oxidative stress and amyloid β-protein toxicity, which are linked with cognitive aging and AD [4,6]. In an animal study, a conditional deletion of the REST gene can also progressively cause age-related neurodegeneration in the mouse brain [4].…”

Section: Introductionmentioning

confidence: 99%

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The rs1277306 Variant of the REST Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population

Lin

Tsai

Kuo

et al. 2017

Dement Geriatr Cogn Disord

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Background/Aims: There is growing evidence that the RE1-silencing transcription factor (REST) gene may contribute to cognitive aging and Alzheimer diseases. In this replication study, we reassessed whether single nucleotide polymorphisms (SNPs) within the REST gene are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. Methods: A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to weigh cognitive functions. Results: Our data showed that the REST rs1277306 SNP was significantly associated with cognitive aging among all subjects (p = 0.0052). Furthermore, the association remained significant for individuals without APOE ε4 allele (p = 0.0092), but not for individuals with at least 1 APOE ε4 allele. This association remained significant after Bonferroni correction. Additionally, we found the interactions between the rs1713985 and rs1277306 SNPs on cognitive aging (p = 0.016). However, the 3-marker haplotype derived from the rs1713985, rs3796529, and rs7680734 SNPs in the REST gene demonstrated no association with cognitive aging. Conclusion: Our study indicates that the REST gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP and APOE-REST interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The rs1277306 Variant of the REST Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population

Lin

Tsai

Kuo

et al. 2017

Dement Geriatr Cogn Disord

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“…In rodents, exercise increases neurogenesis, synaptic plasticity and dendritic spine density (23). Exercise suppresses neuroinflammation, which has been implicated in the pathogenesis of schizophrenia (24,25). Thus, animal models support both neurotrophic and neuroprotective effects of exercise on the brain, although these have yet to been directly demonstrated in the central nervous system of individuals with schizophrenia.…”

Section: Physical Activity and Exercise Interventionsmentioning

confidence: 99%

Emerging behavioral and psychotherapeutic interventions for schizophrenia

O’Donnell¹,

Martin²

2016

Dusunen Adam

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Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats

et al. 2020

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In the brain, REST (Repressor Element-1 Silencing Transcription factor) is a key regulator of neuron cell-specific gene expression. Nuclear translocation of neuronal REST has been shown to be neuroprotective in a healthy ageing context. In contrast, inability to upregulate nuclear REST is thought to leave ageing neurons vulnerable to neurodegenerative stimuli, such as Alzheimer's disease (AD) pathology. Hippocampal and cortical neurons are known to be particularly susceptible to AD-associated neurodegeneration. However, REST expression has not been extensively characterised in the healthy ageing brain. Here, we examined the spatiotemporal immunolocalisation of REST in the brains of healthy ageing wild-type Fischer-344 and transgenic Alzheimer's disease rats (TgF344-AD). Nuclear expression of REST increased from 6 months to 18 months of age in the hippocampus, frontal cortex and subiculum of wild-type rats, but not in TgF344-AD rats. No changes in REST were measured in more posterior cortical regions or in the thalamus. Interestingly, levels of the presynaptic marker synaptophysin, a known gene target of REST, were lower in CA1 hippocampal neurons of 18-month TgF344-AD rats compared to 18-month wild-types, suggesting that elevated nuclear REST may protect against synapse loss in the CA1 of 18-month wild-type rats. High REST expression in ageing wild-type rats did not, however, protect against axonal loss nor against astroglial reactivity in the hippocampus. Taken together, our data confirm that changes in nuclear REST expression are context-, age-and brain region-specific. Moreover, key

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Running for REST: Physical activity attenuates neuroinflammation in the hippocampus of aged mice

Cited by 34 publications

References 25 publications

The rs1277306 Variant of the <b><i>REST</i></b> Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population

The rs1277306 Variant of the <b><i>REST</i></b> Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population

Emerging behavioral and psychotherapeutic interventions for schizophrenia

Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats

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