Association of the iPLA2? Gene With Bipolar Disorder and Assessment of Its Interaction With TRPM2 Gene Polymorphisms.
Association of the iPLA2? gene with bipolar disorder and assessment of its interaction with TRPM2 gene polymorphisms.
Filed under: Addiction Rehab
Psychiatr Genet. 2012 Dec 30;
Xu C, Warsh JJ, Wang KS, Mao CX, Kennedy JL
Altered intracellular calcium homeostasis and oxidative stress are involved in the pathophysiology of bipolar disorder (BD)-I. To explore the genes contributing to these abnormalities, we examined the association with BD of the iPLA2? (PLA2G6), a signaling enzyme that mobilizes the arachidonic acid signaling cascade and activates oxidative stress, and assessed whether it interacts genetically with type 2 transient receptor potential channel gene (TRPM2), an oxidative stress-responsive calcium channel implicated both functionally and genetically in BD-I. Two tag single nucleotide polymorphisms rs4375 and rs3788533 in iPLA2? were genotyped in 446 White case-control individuals and 296 BD families using a 5′-nuclease TaqMan assay. The results were analyzed using ?-test and transmission disequilibrium tests, and Haploview. In a secondary analysis, we tested gene-gene interactions between TRPM2 and iPLA2? on BD vulnerability by logistic regression using a case-only design in PLINK. iPLA2?-rs3788533 showed a borderline association with BD-I in patients with a history of psychosis in both case-control and family designs. Association with BD as a whole was observed in the family study (significant over transmissions of rs3788533-allele C, P=0.015, PBonferroni=0.03, TDTPHASE). A borderline interaction was found between rs749909 within TRPM2 and rs4375 within iPLA2? (Puncorrected=0.009), on the basis of the case-only design analyzed with PLINK. A significant association of iPLA2? variants with BD-I and a trend gene-gene interaction between iPLA2? and TRPM2 provides additional support for the notion that genetic variation in these two functionally implicated candidates contributes toward the risk and pathophysiology of this illness.
HubMed – addiction
Presynaptic dopamine modulation by stimulant self-administration
Filed under: Addiction Rehab
Front Biosci (Schol Ed). 2013; S5: 261-276
Espana RA, Jones SR
The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine.
HubMed – addiction
Rapid dopamine dynamics in the accumbens core and shell: Learning and action
Filed under: Addiction Rehab
Front Biosci (Elite Ed). 2013; E5: 273-288
Saddoris MP, Sugam JA, Cacciapaglia F, Carelli RM
The catecholamine dopamine (DA) has been implicated in a host of neural processes as diverse as schizophrenia, parkinsonism and reward encoding. Importantly, these distinct features of DA function are due in large part to separate neural circuits involving connections arising from different DA-releasing nuclei and projections to separate afferent targets. Emerging data has suggested that this same principle of separate neural circuits may be applicable within structural subregions, such as the core and shell of the nucleus accumbens (NAc). Further, DA may act selectively on smaller ensembles of cells (or, microcircuits) via differential DA receptor density and distinct inputs and outputs of the microcircuits, thus enabling new learning about Pavlovian cues, instrumental responses, subjective reward processing and decision-making. In this review, by taking advantage of studies using subsecond voltammetric techniques in behaving animals to study how rapid changes in DA levels affect behavior, we examine the spatial and temporal features of DA release and how it relates to both normal learning and similarities to pathological learning in the form of addiction.
HubMed – addiction
Strong correlation between diet and development of colorectal cancer.
Filed under: Addiction Rehab
Front Biosci. 2013; 18: 190-8
Cappellani A, Zanghì A, Di Vita M, Cavallaro A, Piccolo G, Veroux P, Lo Menzo E, Cavallaro V, de Paoli P, Veroux M, Berretta M
Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper-middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity. Tobacco smoking acts both locally and systemically on the colorectal mucosa through the production of carcinogenic agents. Finally, the action of alcohol, in association with nicotine addiction, also increases the risk of developing colorectal tumors. Knowledge of dietary and environmental factors is of paramount importance in implementing preventive strategies for colorectal cancer.
HubMed – addiction
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