The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD

Rane, Pallavi; Shields, Jessica; Heffernan, Meghan E.; Guo, Yin; Akbarian, Schahram; King, Jean A.

doi:10.1016/j.neuropharm.2012.01.026

Cited by 64 publications

(48 citation statements)

References 29 publications

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“…Excessive deacetylation of histones may also play a pathogenic role in Parkinson's disease; in this disorder, alpha-synuclein accumulates within the nucleus and binds to histone H3, suppressing its acetylation [53,54]. Many, though not all [55], studies have found that class I/IIa HDAC inhibitors have a beneficial impact on cellular, fly, and rodent models of Parkinson's disease [56][57][58][59][60][61][62][63]. HDAC inhibitors likewise have may have promise in Huntingon's disease, and other disorders caused by polyglutamine expansion in mutant neuronal proteins [64][65][66].…”

Section: Ketones Modulate Protein Acetylationmentioning

confidence: 99%

Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1

2015

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Section: Ketones Modulate Protein Acetylationmentioning

confidence: 99%

Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1

2015

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“…Neurotoxic pesticides and paraquat were shown to increase histone acetylation in mice brains or cell culture models (Song et al, 2010, 2011), and an increasing number of studies reveal protective effects of HDACi on neurons following a neurotoxic-induced insult (Harrison and Dexter, 2013). For example, it was recently shown that trichostatin A selectively rescues mitochondrial fragmentation and cell death induced by MPP+ in human neuroblastoma cells (Zhu et al, 2014), and that sodium butyrate improves locomotor impairment and early mortality in a rotenone-induced Drosophila model of PD (St Laurent et al, 2013), alleviates cognitive deficits in a rat model of PD in the pre-motor deficit stage (Rane et al, 2012), and up-regulates DJ-1 protein expression and protects neurons in cell cultures and mouse models against MPP+ toxicity (Zhou et al, 2011). DJ-1 is involved in the protection of oxidative stress, and mutation of DJ-1 gene cause early-onset PD (Bonifati et al, 2003).…”

Section: Parkinson's Diseasementioning

confidence: 99%

The potential of epigenetic therapies in neurodegenerative diseases

Coppedè

2014

Front. Genet.

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Available treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, do not arrest disease progression but mainly help keeping patients from getting worse for a limited period of time. Increasing evidence suggests that epigenetic mechanisms such as DNA methylation and histone tail modifications are dynamically regulated in neurons and play a fundamental role in learning and memory processes. In addition, both global and gene-specific epigenetic changes and deregulated expression of the writer and eraser proteins of epigenetic marks are believed to contribute to the onset and progression of neurodegeneration. Studies in animal models of neurodegenerative diseases have highlighted the potential role of epigenetic drugs, including inhibitors of histone deacetylases and methyl donor compounds, in ameliorating the cognitive symptoms and preventing or delaying the motor symptoms of the disease, thereby opening the way for a potential application in human pathology.

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“…In one study rats received intra-striatal injections of 6-OHDA and performed an attentional set-shifting task, which involves learning successively complex discriminations within and across sensory modalities (dimensions). Simple and complex discriminations and interdimensional shifts were unaffected by the 6-OHDA lesion, but extradimensional shifting (EDS) was significantly impaired relative to sham controls and unoperated rats [25]. In another study, Bissonette et al [26] lesioned either the orbitofrontal cortex or medial prefrontal cortex (PFC) of mice using NMDA, and trained them on a set-shifting task.…”

Section: Introductionmentioning

confidence: 99%

MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function

Maiti

Gregg

McDonald

2016

Behavioural Brain Research

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In Parkinson's disease, cognitive deficits manifest as fronto-striatally-mediated executive dysfunction, with impaired attention, planning, judgment, and impulse control. We examined changes in executive function in mice lesioned with subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a 3-choice serial reaction-time (SRT) task, which included measures of sustained attention and impulse control. Each trial of the baseline SRT task comprised a pseudo-random pre-cue period ranging from 3 to 8 s, followed by a 1-s cue duration. MPTP impaired all measures of impulsive behavior acutely, but with additional training their performance normalized to saline control levels. When challenged with shorter cue durations, MPTP-lesioned mice had significantly slower reaction times than wild-type mice. When challenged with longer pre-cue times, the MPTP-lesioned mice exhibited a loss of impulse control at the longer durations. In lesioned mice, striatal dopamine was depleted by 54% and the number of tyrosine-hydroxylase-positive neurons in the substantia nigra pars compacta was reduced by 75%. Serotonin (5-HT) was unchanged in the striatum and prefrontal cortex (PFC), but the ratio of 5-hydroxyindolacetic acid (5-HIAA) to 5-HT was significantly reduced in the MPTP group in the PFC. In lesioned mice, prefrontal 5-HIAA/5-HT was significantly correlated with the executive impairments and striatal norepinephrine was associated with slower reaction times. None of the neurochemical measures was significantly associated with behavior in saline-treated controls. Taken together, these results show that prefrontal 5-HT turnover may play a pivotal role in MPTP-induced executive dysfunction.

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The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD

Cited by 64 publications

References 29 publications

Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1

Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1

The potential of epigenetic therapies in neurodegenerative diseases

MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function

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