Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex

Sui, Li; Wang, Yan; Ju, Liu; Chen, Meng

doi:10.1016/j.nlm.2012.03.007

Cited by 91 publications

(88 citation statements)

References 76 publications

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“…Moreover, Seripa and colleagues identified additional SNPs in the Reelin locus that were significantly associated with AD pathogenesis in women (Seripa et al, 2008), in agreement with the study showing that women have a higher risk for AD than men primarily related to the higher density of NFTs (Barnes et al, 2005). Since the identified SNPs are located mainly in CpG islands within the Reelin promoter (Chen et al, 2002), shown to undergo epigenetic modifications as a part of regulatory mechanism of LTP (Levenson et al, 2008, Sui et al, 2012, it would be of highest relevance to further confirm (Kramer et al, 2011) and to check if these SNPs (Seripa et al, 2008) are correlated with a significant increase or decrease of Reelin levels, respectively. In line with Reelin's role in suppressing NFT formation, it is important to mention that elderly people with high AD pathology but no dementia, the so-called high pathology controls (Kramer et al, 2011, Krstic andKnuesel, 2013) differ from AD patients in the amount of NFT load in the frontal cortex (Maarouf et al, 2011).…”

Section: And Promotessupporting

confidence: 61%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD. AbstractAlzheimer`s disease (AD) is one of the largest unmet medical needs of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles (NFTs), the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiology characteristic of late-onset AD.3

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Section: And Promotessupporting

confidence: 61%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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“…Since the only mechanism described for these drugs is DNMT inhibition, albeit through different mechanims (for review see 61), it is possible to speculate that both effects could result from inhibiting DNMT activity. In agreement with that possibility, the infusion of 5-azacytidine (5-AzaC) attenuated the DNA demethylation induced by the intense stimulation of PFC slices (62). Even thought DNMTs are commonly known for their ability to catalyse DNA methylation, they may also act as DNA demethylases (for review see 61).…”

Section: Discussionmentioning

confidence: 93%

Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels

Sales

Joca

2015

Acta Neuropsychiatr.

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Sales AJ, Joca SRL. Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels.Objective: Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressantlike effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated. Methods: Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants). Results: Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/ kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT. Conclusion: These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression. Significant outcomesThe results as given below further support a possible antidepressant-like profile for drugs that inhibit DNA methyltransferases.• Systemic administration of different classes of DNA methyltransferase inhibitors induces antidepressantlike effects.• The association of subeffective doses of DNA methyltransferase inhibitors with subeffective doses of conventional antidepressant drugs induces antidepressant-like effects.

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“…54 In mammals, global levels of histone 3 and 4 acetylation in the amygdala are increased within hours of auditory fear conditioning, 55 and in vitro neuronal stimulation results in increased acetylation at specific IEG promoters in the hippocampus and prefrontal cortex. 48,56 Furthermore, these increases appear to be important for the development of long-term synaptic plasticity. Mice that lack the HAT activity of CBP have impaired long-term memories formation, 57 and bath application of the HDAC inhibitor TSA enhances the formation of LTP in hippocampal slices.…”

Section: Activity-dependent Chromatin Opening Via Histone Modificationmentioning

confidence: 99%

A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

Nagy

Vaillancourt

Turecki

2018

Genes Brain and Behavior

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Chronic stressors, during developmental sensitive periods and beyond, contribute to the risk of developing psychiatric conditions, including major depressive disorder (MDD). Epigenetic mechanisms including DNA methylation and histone modifications, at key stress response and neurotrophin genes, are increasingly implicated in mediating this risk. Although the exact mechanisms through which stressful environmental stimuli alter the epigenome are still unclear, research from the learning and memory fields indicates that epigenomic marks can be altered, at least in part, through calcium-dependent signaling cascades in direct response to neuronal activity. In this review, we highlight key findings from the stress, MDD, and learning and memory fields to propose a model where stress regulates downstream cellular functioning through activity-dependent epigenetic changes. Furthermore, we suggest that both typical and novel antidepressant treatments may exert positive influence through similar, activity-dependent pathways.

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Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex

Cited by 91 publications

References 76 publications

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels

A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

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