Abstract:
:Human studies suggest that a variety of prenatal stressors are related to high risk for cognitive and behavioral abnormalities associated with psychiatric illness (Markham and Koenig, 2011). Recently, a downregulation in the expression of GABAergic genes (i.e., glutamic acid decarboxylase 67 and reelin) associated with DNA methyltransferase (DNMT) overexpression in GABAergic neurons has been regarded as a characteristic phenotypic component of the neuropathology of psychotic disorders (Guidotti et al., 2011). Here, we characterized mice exposed to prenatal restraint stress (PRS) in order to study neurochemical and behavioral abnormalities related to development of schizophrenia in the adult. Offspring born from non-stressed mothers (control mice) showed high levels of DNMT1 and 3a mRNA expression in the frontal cortex at birth, but these levels progressively decreased at post-natal days (PND) 7, 14, and 60. Offspring born from stressed mothers (PRS mice) showed increased levels of DNMTs compared to controls at all time-points studied including at birth and at PND 60. Using GAD67-GFP transgenic mice, we established that, in both control and PRS mice, high levels of DNMT1 and 3a were preferentially expressed in GABAergic neurons of frontal cortex and hippocampus. Importantly, the overexpression of DNMT in GABAergic neurons was associated with a decrease in reelin and GAD67 expression in PRS mice in early and adult life. PRS mice also showed an increased binding of DNMT1 and MeCP2, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine in specific CpG-rich regions of the reelin and GAD67 promoters. Thus, the epigenetic changes in PRS mice are similar to changes observed in the post-mortem brains of psychiatric patients. Behaviorally, adult PRS mice showed hyperactivity and deficits in social interaction, prepulse inhibition, and fear conditioning that were corrected by administration of valproic acid (a histone deacetylase inhibitor) or clozapine (an atypical antipsychotic with DNA-demethylation activity). Taken together, these data show that prenatal stress in mice induces abnormalities in the DNA methylation network and in behaviors indicative of a schizophrenia-like phenotype. Thus, PRS mice may be a valid model for the investigation of new drugs for schizophrenia treatment targeting DNA methylation. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Matrisciano F,Tueting P,Dalal I,Kadriu B,Grayson DR,Davis JM,Nicoletti F,Guidotti Adoi
10.1016/j.neuropharm.2012.04.013subject
Has Abstractpub_date
2013-05-01 00:00:00pages
184-94eissn
0028-3908issn
1873-7064pii
S0028-3908(12)00149-9journal_volume
68pub_type
杂志文章abstract::Alcohol produces many subjective and objective effects in man including pleasure, sedation, anxiolysis, plus impaired eye movements and memory. In human volunteers we have used a newly available GABA-A/benzodiazepine receptor inverse agonist that is selective for the alpha5 subtype (a5IA) to evaluate the role of this ...
journal_title:Neuropharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.neuropharm.2007.08.008
更新日期:2007-12-01 00:00:00
abstract::The selective benzodiazepine antagonist RO 15-1788, labelled with carbon 11 [11C] RO 15-1788, as a specific marker, together with positron emission tomography, allows the in vivo study of benzodiazepine receptors in primates. In addition, when coupled with recordings of electroencephalographic activity, this method of...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90171-7
更新日期:1987-10-01 00:00:00
abstract::Owing to a broad spectrum of functions performed by neuropeptides, this class of signaling molecules attracts an increasing interest. One of the key steps in the regulation of biological activity of neuropeptides is proteolytic conversion or degradation by proteinases that change or terminate biological activity of na...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2020.108137
更新日期:2020-09-15 00:00:00
abstract::Tobacco addiction is a chronic disorder that is characterized by craving for tobacco products, withdrawal upon smoking cessation, and relapse after periods of abstinence. Previous studies demonstrated that systemic administration of α2-adrenergic receptor agonists attenuates stress-induced reinstatement of drug seekin...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2010.09.013
更新日期:2011-02-01 00:00:00
abstract::Multiple administrations of methamphetamine to rats produced elevated concentrations of substance P-like immunoreactivity within the substantia nigra, an effect which is believed to be mediated by increases in dopaminergic activity induced by methamphetamine. The results reported here demonstrate that the effect of me...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90139-5
更新日期:1986-11-01 00:00:00
abstract::Opioids evoke analgesia through activation of opioid receptors (predominantly the μ opioid receptor) in the central nervous system. Opioid receptors are abundant in multiple regions of the central nervous system and the peripheral nervous system including enteric neurons. Opioid-related adverse effects such as constip...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2017.12.032
更新日期:2018-03-15 00:00:00
abstract::Regional differences are known in the serotonin-induced modulation of neuronal activity within the amygdala. This in vitro study in rats focuses on analyzing the ionic mechanism underlying serotonin-induced depolarization in the lateral amygdala. Serotonin depolarized membrane potential by 5 mV, which is underlain by ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.03.007
更新日期:2014-07-01 00:00:00
abstract::Here, we define a protophenotype as an endophenotype that has been conserved during evolution. Social feeding in Caenorhabditis elegans may be an example of a protophenotype related to asociality in schizophrenia. It is regulated by the highly conserved neuropeptide Y receptor, NPR-1, and we speculated that social fee...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.12.027
更新日期:2015-05-01 00:00:00
abstract::Protease activity correlates with depressive or suicidal behaviors, with calpain activation being especially implicated in depression-like behaviors. However, the role of calpain in depression-like behaviors is currently unknown. In this study, the lipopolysaccharide (LPS) - and chronic unpredictable mild stress (CUMS...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108175
更新日期:2020-09-01 00:00:00
abstract::5-hydroxytryptamine 1 (5-HT1) receptor blockade in combination with serotonin reuptake inhibition may provide a more rapid elevation of synaptic 5-HT compared to serotonin reuptake alone, by blocking the inhibitory effect of 5-HT1 receptor activation on serotonin release. GSK588045 is a novel compound with antagonist ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.11.017
更新日期:2015-05-01 00:00:00
abstract::Stem cell research offers enormous potential for treating many diseases of the nervous system. At present, therapeutic strategies in stem cell research segregate into two approaches: cell transplantation or endogenous cell stimulation. Realistically, future cell therapies will most likely involve a combination of thes...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2009.10.005
更新日期:2010-05-01 00:00:00
abstract::The locomotor activity of female rats was recorded during 10-min sessions in a circular open-field apparatus after the administration of vehicle or drug. Dose-response curves were obtained for seven neuroleptic drugs both alone (spontaneous activity) and in combination with 1.0 mg/kg of d-amphetamine. Haloperidol, pim...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(84)90004-2
更新日期:1984-08-01 00:00:00
abstract::Elimination of brain cholesterol occurs in the form of 24S-hydroxycholesterol (24S-HCh) that may modulate physiological processes outside the brain. Here, using microelectrode recording of postsynaptic responses (end-plate potentials, EPPs) and fluorescent marker (FM1-43) for endo-exocytosis we studied the effects of ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.03.018
更新日期:2019-05-15 00:00:00
abstract::Postsynaptic Density Protein-95 (PSD-95) is a major scaffolding protein in the excitatory synapses in the brain and a critical regulator of synaptic maturation for NMDA and AMPA receptors. PSD-95 deficiency has been linked to cognitive and learning deficits implicated in neurodevelopmental disorders such as autism and...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108277
更新日期:2020-11-15 00:00:00
abstract::Orexin contributes to the expression of the cardiovascular and behavioural response of some forms of stress, including novelty stress. Thus, Almorexant, a dual receptor antagonist that blocks the two known orexin receptors, Ox1R and Ox2R, reduces these responses. However, it is not known if the reduction results from ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.09.012
更新日期:2015-02-01 00:00:00
abstract::In this study, we analysed the implication of superoxide (O2-.) and nitric oxide (NO.) free radicals and their resulting product peroxynitrite (ONOO-) in the neuronal death induced by the activation of the glutamatergic receptor of the N-methyl-D-aspartate (NMDA) subtype using cultured cerebellar granule cells. The NO...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(93)90020-4
更新日期:1993-11-01 00:00:00
abstract::Hormones may produce long-term effects on excitability by regulating K+ channel gene expression. Previous studies demonstrated that administration of dexamethasone, a glucocorticoid receptor agonist, to adrenalectomized rats, rapidly induces Kv1.5 K+ channel expression in the ventricle of the hear. Here, RNase protect...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Calcium currents in the inferior colliculus (IC) are thought to play an important role in ethanol withdrawal hyperexcitability. Here, we report on the modulation of Ca(2+) channel currents in acutely dissociated IC neurons of rats, exhibiting higher incidence of audiogenic seizures when subjected to ethanol withdrawal...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00191-6
更新日期:2003-09-01 00:00:00
abstract::In the rat brain, gamma-hydroxybutyric-acid (GHB) increases the concentrations of 3alpha-hydroxy,5alpha-pregnan-20-one (allopregnanolone, 3alpha,5alpha-THP) and 3alpha,21-dihydroxy,5alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone/3alpha,5alphaTHDOC), two neurosteroids acting as positive allosteric modulators o...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.01.026
更新日期:2005-07-01 00:00:00
abstract::Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symp...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.11.003
更新日期:2013-04-01 00:00:00
abstract::G protein-coupled receptor 35 (GPR35) is an orphan G protein-coupled receptor (GPCR) that can be activated by kynurenic acid at high micromolar concentrations. A previously unappreciated mechanism of action of GPR35 has emerged as a Gαi/o-coupled inhibitor of synaptic transmission, a finding that has significant impli...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2015.07.035
更新日期:2017-02-01 00:00:00
abstract::N-methyl-d-aspartate receptors (NMDARs) are profound regulators of glutamate neurotransmission and behavior. To coordinate components of the limbic system, the dorsal and ventral striatum integrate cognitive and emotional information towards the execution of complex behaviors. Striatal outflow is conveyed by medium sp...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.03.026
更新日期:2017-01-01 00:00:00
abstract::The stable transcription factor ΔFosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of ΔFosB in the striatum enhances the rewarding properties of morphine and cocaine. However, the mechanistic basis for these observations is incompletely understood. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.08.046
更新日期:2011-12-01 00:00:00
abstract::Alpha2-adrenergic drugs modulate cortical arousal and EEG. However, the role of individual alpha2-adrenoceptor (alpha(2)-AR) subtypes in these functions is not clear. We investigated the role of alpha(2C)-ARs in the modulation of baseline cortical EEG activity and EEG responses to the alpha(2)-AR selective agonist, de...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00305-2
更新日期:2002-12-01 00:00:00
abstract::Administration of 0.13% lead acetate solution as drinking fluid to breeding mice was without significant effect on the numbers of live or dead births or on weight of pups at 1 day. The appearance of fur was delayed and the body weights at 21 days and 31-38 weeks were smaller than in controls. On weaning, the treated o...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90036-5
更新日期:1986-02-01 00:00:00
abstract::Cyclosporine, a calcineurin inhibitor, significantly enhances spontaneous acetylcholine release after a brief tetanus and potentiates the effect of phorbol 12,13-dibutyrate. Both actions are prevented by the protein kinase C inhibitor, bisindolylmaleimide iodide. Protein kinase C and calcineurin thus play important ro...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00178-6
更新日期:1999-01-01 00:00:00
abstract::The effects of the pure narcotic antagonists, naloxone and naltrexone, and their quaternary derivatives, methylnaloxone and methylnaltrexone, were examined in reversing the catalepsy induced by morphine in rats. Morphine, 20 mg/kg, induced rigid catalepsy which attained a peak effect (as manifested by duration of cata...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90246-0
更新日期:1983-03-01 00:00:00
abstract::G protein regulated inward rectifying potassium channels (GIRKs) are activated by G protein coupled receptors (GPCRs) via the G protein betagamma subunits. However, little is known about the effects of different GPCRs on the deactivation kinetics of transmitter-mediated GIRK currents. In the present study we investiga...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00080-0
更新日期:2000-09-01 00:00:00
abstract::YM992, (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride, exhibited the biochemical profile of a selective serotonin (5-HT) reuptake inhibitor (SSRI) with 5-HT2A receptor antagonistic activity. YM922 showed the same high affinity as fluoxetine against the 5-HT reuptake site (Ki = 21 nM) and a similar...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(96)00079-2
更新日期:1996-01-01 00:00:00
abstract::Morphine alters affective states in humans and produces reinforcement in humans and animal subjects. Therefore, the present study was designed to determine whether morphine affected the functional activity in brain structures involved in emotion and motivation. Since opioid-induced analgesia largely reflects an influe...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90195-h
更新日期:1991-02-01 00:00:00