Changes in the expression of transthyretin and protein kinase Cγ genes in the prefrontal cortex in response to naltrexone.
Summary of "Changes in the expression of transthyretin and protein kinase Cγ genes in the prefrontal cortex in response to naltrexone."
Naltrexone, an opioid receptor antagonist, has been approved for clinical use in the treatment of alcohol dependence. In the present study, we examined the underlying mechanisms of naltrexone by investigating the pharmacogenomic variations in the brain regions associated with alcohol consumption. A complementary DNA microarray analysis was used to profile gene expression changes in the hippocampus and prefrontal cortex (PFC) of C57BL/6 mice injected with naltrexone following ethanol treatment. Intraperitoneal administration of 200μl (16mg/kg) of naltrexone for 4 weeks caused alterations in the expression of a wide range of hippocampal (394) and PFC (566) genes in ethanol-treated mice. Ingenuity Pathway Analysis (IPA) software was used to search for biological pathways and interrelationships between gene networks in the subsets of candidate genes that were altered in the naltrexone-treated PFC and hippocampus. We found gene networks associated with cell morphology, cell death, nervous system development and function, and neurological disease. Confirmation studies using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that the expression of transthyretin (TTR) and protein kinase C (PKC)γ were increased in the PFC but not in the hippocampus of naltrexone-treated mice. In conclusion, the present study demonstrates a pharmacogenomic response to naltrexone in the brains of ethanol-consuming mice. These findings provide a basis for conducting pharmacogenetic research on the effect of naltrexone in specific brain areas, which would enhance our understanding of the underlying causes and possible treatments of alcohol use disorders.
Affiliation
Department of Neuropsychiatry, Konkuk University School of Medicine, Seoul, Republic of Korea.
Journal Details
This article was published in the following journal.
Name: Neuroscience letters
ISSN: 1872-7972
Pages: 288-93
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21111029
- DOI: http://dx.doi.org/10.1016/j.neulet.2010.11.049
Medical and Biotech [MESH] Definitions
Prefrontal Cortex
The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin.
Calcium-calmodulin-dependent Protein Kinase Type 1
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
Epistasis, Genetic
A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.
Map Kinase Signaling System
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Calcium-calmodulin-dependent Protein Kinase Kinase
A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.
PubMed Articles
Changes in the expression of psychosis related genes, including SELENBP1, MT1X, MT2A, SST1 and TAC1, have been identified in the prefrontal cortex. To test whether these changes are psychosis markers,...
Transthyretin is a plasma hormone carrier protein associated with hereditary and senile forms of systemic amyloid disease, wherein slow tetramer disassembly is thought to be an obligatory step. Plasma...
Prolonged stress has been associated with altered synaptic plasticity but little is known about the molecular components and mechanisms involved in the stress response. In this study, we examined the...
Prefrontal Cortex Tunes Category Selectivity in Visual Association Cortex.
Different categories of visual objects evoke distinct bottom-up sensory responses in visual association cortex. Although numerous lines of evidence suggest this category selectivity, the degree to whi...
Prefrontal serotonin 5-HT(2) receptors have been linked to the pathogenesis and treatment of affective disorders, yet their function in psychiatric vulnerability is not known. Here, we examine the eff...
Clinical Trials
The main objective of this study is to examine the effects of magnetic stimulation on the prefrontal cortex. We plan to use low frequency, repeated transcranial magnetic stimulation (1 Hz...
Epidural Cortical Stimulation for Depression
Objective: Chronic epidural cortical stimulation (ECS) involves the neurosurgical placement of an electric wire on the surface of the brain with intermittent activation. Over time, ECS mod...
Investigating the Cognitive Processes That Underlie Social Knowledge and Behavior
The purpose of the protocol is to localize the neural regions and systems mediating the forms of knowledge representations hypothesized by the principal investigator to be stored in the hu...
The purpose of this research study is to: - see if gefitinib pills can shrink Stage 1 or 2 non-small cell lung cancers before surgery - see if your non-small cell lung c...
Trial to Evaluate Safety and Tolerability of ALN-TTR01 in Transthyretin (TTR) Amyloidosis
The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of a single dose of ALN-TTR01 in patients with transthyretin (TTR) mediated amyloi...
