A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal

Mueller, Scott W.; MacLaren, Robert

doi:10.1016/j.alcohol.2014.11.006

Cited by 11 publications

(7 citation statements)

References 25 publications

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“…Several studies reported no difference in baseline serum BDNF levels between alcoholic patients and controls (Geoffroy and Noble ), whereas other authors observed a modest increase in BDNF levels in early alcohol withdrawal (Reynolds et al . ) or a decrease in 2‐week alcohol withdrawal patients (Köhler et al . ).…”

Section: Discussionmentioning

confidence: 99%

Alcohol‐induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats

et al. 2018

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Chronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticity and connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cognitive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitive impairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulating levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent subjects with alcohol use disorders (AUDs, N = 58, average of 17.9 years of problematic use and 4.3 months of abstinence) compared with healthy control subjects (N = 22). This association was also explored in a pre-clinical model of adolescent rats chronically exposed to alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5-10-20 percent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairment associated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentration showed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasma levels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampal Bdnf mRNA levels and recognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neurotrophic (Bdnf and Ntf-3) and neurogenic (Mki67, Sox2, Dcx, Ncam1 and Calb1) factors, associated to a deactivation of the neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a relevant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and suggest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.

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Section: Discussionmentioning

confidence: 99%

Alcohol‐induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats

et al. 2018

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“…For example, we find H3K27me3 peaks following treatment in Glial cell line-derived neurotrophic factor ( Gdnf ) and Anaplastic lymphoma kinase ( Alk ) genes, and increased H3K4me3 peaks in the ethanol samples at the Glutamate Receptor, Ionotropic, AMPA 1 ( Gria1 ) gene. These genes have been reported to be dysregulated by ethanol exposure (Carnicella et al, 2009; Heberlein et al, 2010; Lasek et al, 2011; Wolen et al, 2012; Reynolds et al, 2015; Dutton et al, 2017). With regard to H3K4me3 analysis, there is 0.004% chance of observing this level of overlap with the literature findings by chance using a hypergeometric test, suggesting a high level of correlation between H3K4me3 and gene expression.…”

Section: Discussionmentioning

confidence: 99%

Stable Histone Methylation Changes at Proteoglycan Network Genes Following Ethanol Exposure

et al. 2018

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Alcohol use disorder (AUD) is a chronic mental illness in which patients often achieve protracted periods of abstinence prior to relapse. Epigenetic mechanisms may provide an explanation for the persisting gene expression changes that can be observed even after long periods of abstinence and may contribute to relapse. In this study, we examined two histone modifications, histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3), in the prefrontal cortex of Withdrawal Seizure Resistant (WSR) mice 21 days after 72 h of ethanol vapor exposure. These histone modifications were selected because they are associated with active promoters (H3K4me3) and repressed gene expression in a euchromatic environment (H3K27me3). We performed a genome-wide analysis to identify differences in H3K4me3 and H3K27me3 levels in post-ethanol exposure vs. control mice by ChIP-seq. We detected a global reduction in H3K4me3 peaks and increase in H3K27me3 peaks in post-ethanol exposure mice compared to controls, these changes are consistent with persistent reductions in gene expression. Pathway analysis of genes displaying changes in H3K4me3 and H3K27me3 revealed enrichment for genes involved in proteoglycan and calcium signaling pathways, respectively. Microarray analysis of 7,683 genes and qPCR analysis identified eight genes displaying concordant regulation of gene expression and H3K4me3/H3K27me3. We also compared changes in H3K4me3 and/or H3K27me3 from our study with changes in gene expression in response to ethanol from published literature and we found that the expression of 52% of the genes with altered H3K4me3 binding and 40% of genes with H3K27me3 differences are altered by ethanol exposure. The chromatin changes associated with the 21-day post-exposure period suggest that this period is a unique state in the addiction cycle that differs from ethanol intoxication and acute withdrawal. These results provide insights into the enduring effects of ethanol on proteoglycan and calcium signaling genes in the brain.

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“…However, the increase in these markers of plasticity eventually subsides. Alcoholic patients going through withdrawal show an acute transient increase in plasma concentrations of BDNF levels, but not NGF levels [ 83 , 84 ]. Furthermore, the intensity of acute alcohol withdrawal symptoms have been correlated with an increase in BDNF serum levels [ 46 ], which was taken as evidence that BDNF may be involved in neuroadaptation during the early alcohol withdrawal period.…”

Section: Discussionmentioning

confidence: 99%

Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure

2016

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Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and beta-nerve growth factor (β-NGF) in the prefrontal cortex and hippocampus were also assessed at different time-points: during CET, following acute abstinence (48-hrs), and after protracted abstinence (6–8 wks). Our results revealed that an adolescent onset of CET leads to increased EtOH consumption that persisted into adulthood. In both adult and adolescent onset CET groups, there were significant long-term reductions in prefrontal cortical mBDNF and β-NGF levels. However, only adult onset CET rats displayed decreased hippocampal BDNF levels. Spatial memory, assessed by spontaneous alternation and delayed alternation, was not significantly affected by CET as a function of age of drinking onset, but higher blood–EtOH levels were correlated with lower spontaneous alternation scores. Regardless of the age of onset, EtOH exposed rats were impaired on non-spatial discrimination learning and displayed inflexible behavioral patterns upon reversal learning. Our results indicate that adolescent EtOH exposure changes long-term consumption patterns producing behavioral and neural dysfunctions that persist across the lifespan.

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A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal

Cited by 11 publications

References 25 publications

Alcohol‐induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats

Alcohol‐induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats

Stable Histone Methylation Changes at Proteoglycan Network Genes Following Ethanol Exposure

Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure

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