Abstract：
:The CHRNA7 gene encoding the α7 nicotinic acetylcholine receptor (nAChR) has repeatedly been linked with schizophrenia and the P50 sensory gating deficit. The α7 nAChR is considered a promising drug target for treatment of cognitive dysfunction in schizophrenia and improves memory and executive functions in patients and healthy individuals. However, clinical trials with pro-cognitive drugs are challenged by large inter-individual response variations and these have been linked to genotypic variations reducing CHRNA7 expression and α7 nAChR function. Genetic variants as well as environmental conditions may cause epigenetic dysregulation and it has previously been found that DNA methylation of a region surrounding the transcription start site of CHRNA7 is important for tissue specific regulation and gene silencing. In the present study we identify two additional regions involved in epigenetic regulation of the CHRNA7 promoter. In human temporal cortex we find large variations in expression of CHRNA7 and establish evidence for a significant correlation with DNA methylation levels of one region. We then establish evidence that genotypic variations can influence methylation levels of the CHRNA7 promoter. Epigenetic dysregulation can be reversed by pharmacological intervention and in HeLa cells. Valproate, a commonly used mood stabiliser, caused demethylation and increased CHRNA7 expression in HeLA cells. Similar demethylation effect and increased CHRNA7 expression was obtained in SH-SY5Y cells stimulated concomitantly with valproate and nicotine. In summary, both genetic and epigenetic information could be useful to predict treatment outcomes in patients and epigenetic modulation may serve as a mechanism for potentiating the effects of α7 nAChR agonists.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Dyrvig M,Mikkelsen JD,Lichota Jdoi
10.1016/j.neulet.2019.04.015subject
Has Abstractpub_date
2019-06-21 00:00:00pages
145-152eissn
0304-3940issn
1872-7972pii
S0304-3940(19)30249-6journal_volume
704pub_type
杂志文章abstract：:The expression of aquaporin-1 (AQP1) protein, a water channel, in the choroid plexus epithelium was examined in the rat to determine the role of AQP1 in the pathophysiology of systemic hyponatremia. Systemic hyponatremia was produced by coadministration of 30 ml hypotonic dextrose solution (140 mM) intraperitoneally a...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2005.10.060
更新日期：2006-02-27 00:00:00
abstract：:The study investigated the effects of metabolic syndrome on urinary bladder nerve-growth factor (NGF) and p75(NTR) expression in fructose-fed obese rats. Age-matched male Wistar rats were divided into four groups; group I: normal control rats; group II: 6-week fructose-fed rats (FR); group III: 9-week FR; and group IV...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2008.06.008
更新日期：2008-08-15 00:00:00
abstract：:Microglia are resident immune cells of brain and activated by peripheral tissue injury. In the present study, we investigated the possible induction of several microglial surface immunomolecules in the spinal cord, including leukocyte common antigen (LCA/CD45), MHC class I antigen, MHC class II antigen, Fc receptor, a...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2008.11.009
更新日期：2009-01-16 00:00:00
abstract：:We have previously shown that 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, inhibits proliferation of neuroblastoma cells in culture. We have now tested whether the effect of H7 is mediated by MAP kinase and Raf. It is shown that, in Neuro 2a cells, activation of protein kinase...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(96)12867-6
更新日期：1996-08-16 00:00:00
abstract：:Sex differences are often reported in spatial abilities. However, some studies show conflicting results, which can be ascribed to the complexity of the variables involved in the visuo-spatial domain. Until a few years ago, it was widely accepted that men outperformed women on almost all spatial tasks. However, recentl...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2007.12.044
更新日期：2008-02-20 00:00:00
abstract：:In this study, we investigated the role of nitric oxide (NO) in neuronal cell death in the lipopolysaccharide (LPS)-treated rat hippocampal slice culture. Neuronal cell death was induced after a LPS treatment in a rat hippocampal slice. The region and time course of the cell death caused by LPS were different from tho...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(03)00697-9
更新日期：2003-09-25 00:00:00
abstract：:Cerebellar granule neurons can be maintained in culture in a medium containing high serum and depolarising levels of KCl. When serum is removed and the KCl levels lowered from 25 to 5 mM, the cells undergo apoptosis. Apoptosis can be prevented by inhibitors of transcription or translation, suggesting a need for macrom...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(01)01687-1
更新日期：2001-04-20 00:00:00
abstract：:Fetal intrauterine growth restriction generates chronic hypoxia due to placental insufficiency. Despite the hemodynamic process of blood flow, redistributions are taking place in key organs such as the fetal brain during intrauterine growth restriction, in order to maintain oxygen and nutrients supply. The risk of sho...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2014.09.051
更新日期：2015-01-01 00:00:00
abstract：:The morphology and function of sciatic nerve were investigated in spontaneously hypertensive rats (SHR), either control or hydralazine-treated, and in normotensive Wistar Kyoto rats of 6 months of age. In control SHR decreased percentages of class I fibers (20-15 microm in diameter), of axonal NFP-H 200 kDa neurofilam...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2004.03.014
更新日期：2004-05-20 00:00:00
abstract：:Within the normal inner ear, there are elements that belong to the immune system. Different inner ear disorders can be explained by autoimmune mechanisms, affecting both humoral and cellular immunity. Melatonin, the principal hormone of the pineal gland, modulates the immune system and extensively participates in the ...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(97)00844-6
更新日期：1997-11-28 00:00:00
abstract：:We compared the modulation of GABA (gamma-aminobutyric acid)-activated currents by benzodiazepines in recombinant GABAA receptors containing either one of two alpha subunits, alpha 1 or alpha 6. Lüddens et al. (Nature, 346 (1990) 648-651) have previously demonstrated that the alpha 6 subunit is part of a cerebellar re...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(91)90389-b
更新日期：1991-09-16 00:00:00
abstract：:The influence of chronic arthritic pain upon the levels of mRNA encoding prodynorphin (mRNADYN) in the spinal cord of rats was evaluated by use of the RNA blot technique. Rats were rendered arthritic by inoculation of the tail-base with a suspension of Mycobacterium butyricum. Three weeks post inoculation, levels of m...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(87)90037-1
更新日期：1987-01-02 00:00:00
abstract：:Nerve ligation injury in rats may represent a useful model of some clinical neuropathic pains. Activation of N-methyl-D-aspartate (NMDA) receptors may maintain central sensitivity and contribute to neuropathic pain. Here, nerve injury was produced by unilateral ligation of the L5 and L6 spinal roots of the sciatic ner...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(95)12022-v
更新日期：1995-10-20 00:00:00
abstract：:Cocaethylene is an active cocaine metabolite that targets mammalian neural reward pathways and thus contributes to the reinforcing and addictive properties of ethanol and cocaine. Using gas chromatography-mass spectrometry, we find that fruit flies (Drosophila melanogaster) possess a cellular mechanism through which c...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(99)00156-1
更新日期：1999-03-26 00:00:00
abstract：:Basal serotonin (5-HT) release, measured in the presence of imipramine, was significantly reduced in slices of hippocampus, n. accumbens and frontal cortex from rats subjected to forced swim test and chronic isolation. Only in the hippocampus, in the two animal models of depression, K-stimulated release was increased....
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(93)90584-8
更新日期：1993-11-12 00:00:00
abstract：:Light microscopic immunohistochemistry was used to investigate the presence and distribution of chromogranin A-like immunoreactivity in the human anal canal. In the anal transitional zone (ATZ), anal duct and anal gland epithelium, a varied number of mostly elongated cells strongly stained for CGA, using an antibody d...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(91)90394-9
更新日期：1991-09-16 00:00:00
abstract：:Activation of central neuropeptide Y (NPY) receptors is known to produce several behavioral effects, including feeding, modulation of memory and antagonism of behavioral effects of stress. In addition, experiments in knock-out and transgenic mice have suggested a possible role of NPY regulation of voluntary ethanol in...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(02)00904-7
更新日期：2002-10-25 00:00:00
abstract：:This review attempts to explain the symptoms experienced by patients with inflammatory neuropathies by pathophysiological events. The emphasis is not on the primary events that may cause a particular illness but on downstream events taking place in peripheral nerves or muscles. Symptoms that will be discussed include ...
journal_title：Neuroscience letters
pub_type： 杂志文章,评审
doi：10.1016/j.neulet.2014.12.009
更新日期：2015-06-02 00:00:00
abstract：:The expression of class I and class II histocompatibility antigens by myelin basic protein (MBP)-positive oligodendrocytes, in response to exogenous cytokines, has been investigated in vitro. It has been found that interferon-gamma (IFN-gamma), although capable of class I induction, does not induce class II on oligode...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(91)90154-l
更新日期：1991-02-11 00:00:00
abstract：:Dysregulated brain glucose metabolism and lactate accumulation are seen following traumatic brain injury (TBI). The underlying molecular mechanism is poorly understood. Pyruvate dehydrogenase (PDH), the rate-limiting enzyme coupling cytosolic glycolysis to mitochondrial citric acid cycle, plays a critical role in main...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2009.01.047
更新日期：2009-04-17 00:00:00
abstract：:A random sample of 60 late-onset Alzheimer's disease (AD) cases from a population-based study were apolipoprotein E (apoE) genotyped and clinically examined with a 3-year interval. The epsilon 4 allele carriers had a significantly lower age of disease onset compared to non-epsilon 4 carriers. However, no significant d...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(94)11107-t
更新日期：1995-01-02 00:00:00
abstract：:Peripheral nerve damage causes a dramatic alteration to the gene expression in primary sensory neurons, changes within the neuronal cell body giving rise to an altered phenotype, adapted for axonal regeneration. Such changes suggest an alteration in activity, or levels, of cellular transcription factors. The POU famil...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(96)12514-3
更新日期：1996-04-05 00:00:00
abstract：:Excitotoxin lesion of nucleus basalis with kainate or ibotenate results in degeneration of cholinergic neurones and a subsequent cholinergic deficit in cerebral cortex ipsilateral to the lesion. This lesion is accompanied by a massive increase in ornithine decarboxylase (ODC) activity in ipsilateral cortex, which was ...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(90)90364-f
更新日期：1990-03-26 00:00:00
abstract：:We investigated a possible involvement of the prion protein in ventilatory control in four groups of mice, those deficient for the prion protein (PrP(c)), those overexpressing the prion protein, and two groups of genetically and age-matched controls. Ventilatory patterns of unrestrained mice were measured in a whole-b...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(01)02536-8
更新日期：2002-04-26 00:00:00
abstract：:Actions of the polyamines spermine and spermidine on NMDA-induced currents were examined in cultured hippocampal neurons from embryonic rat. In whole-cell patch experiments using voltage-clamp, spermine (300 microM) produced about a two-fold potentiation of responses to NMDA (at -70 mV in the presence of saturating gl...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(93)90495-7
更新日期：1993-04-02 00:00:00
abstract：:The mechanisms underlying aggregate formation in age-related neurodegenerative diseases remain not well understood. Here we investigated whether dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) is involved in the formation of regulator of calcineurin 1 (RCAN1) aggregates. We show that RCAN1 s...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/j.neulet.2013.08.066
更新日期：2013-10-25 00:00:00
abstract：:We investigated the effects of aging on the neuroanatomical sex dimorphisms of the rat hypothalamic ventromedial nucleus (VMN). Stereological methods were used to estimate the volume of the VMN and the total number and size of its neurons, including their dendritic trees, in males and females aged 6 and 24 months. No ...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/s0304-3940(01)02294-7
更新日期：2001-11-13 00:00:00
abstract：:The phenylquinoline, PK 8165 (5-25 mg/kg), produced dose-related reductions in locomotor activity, rearing and exploratory head-dipping in a holeboard. Neither Ro 15-1788 (1, 10 or 20 mg/kg) nor CGS 8216 (1 or 10 mg/kg) was able to reverse the reductions in locomotor activity or rearing. This suggests that at least so...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(84)90486-5
更新日期：1984-09-07 00:00:00
abstract：:Ibotenate and trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) are rigid analogues of glutamate. Ibotenate has been shown to activate phosphoinositide hydrolysis in rat brain slices. We now report that trans-ACPD also stimulates phosphoinositide hydrolysis but with much higher potency and efficacy than...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(90)90555-n
更新日期：1990-02-05 00:00:00
abstract：:In order to study the influence of curare and atropine on the gamma-aminobutyric acid (GABA)-evoked chloride current, we have investigated cultures of hippocampal and septal region neurons from embryonic rats (E18). The neurons were cultured under the trophic influence of spatially separated astrocytes in serum-free m...
journal_title：Neuroscience letters
pub_type： 杂志文章
doi：10.1016/0304-3940(88)90085-7
更新日期：1988-11-11 00:00:00
