Genotype effects on neurodegeneration and neuroadaptation in monoaminergic neurotransmitter systems

Heinz, Andreas; Goldman, David

doi:10.1016/s0197-0186(00)00057-7

Cited by 32 publications

(16 citation statements)

References 65 publications

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“…2010). This polymorphism in the hDAT gene has been consistently associated with cessation of smoking, obesity in smokers, ADHD, schizophrenia, and alcoholism (Heinz and Goldman 2000). However, the mechanism through which this, or other variants, in the hDAT gene might affect the expression and function of dopamine neurotransmission remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

et al. 2016

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IntroductionThe dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug‐dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology.MethodsIn this study, we produced DA neurons differentiated using iPSCs derived from opioid‐dependent and control subjects carrying different 3′ VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC‐derived human DA neurons are also examined.ResultsWe present the first evidence suggesting that the 3′ VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC‐derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid‐dependent iPSC cell lines.ConclusionsOur data suggest that human iPSC‐derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

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Section: Discussionmentioning

confidence: 99%

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

et al. 2016

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“…A study of 14 abstinent alcoholics and 11 controls reported the opposite result (Heinz et al, 2000), but this could reflect changes in striatal DAT protein associated with long-term alcohol use or rebound during abstinence (Heinz & Goldman, 2000). …”

Section: Biological Plausibilitymentioning

confidence: 99%

Interactions between early parenting and a polymorphism of the child's dopamine transporter gene in predicting future child conduct disorder symptoms.

Lahey¹,

Rathouz²,

Lee³

et al. 2011

Journal of Abnormal Psychology

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Mounting evidence suggests that genetic risks for mental disorders often interact with the social environment, but most studies still ignore environmental moderation of genetic influences. We tested interactions between maternal parenting and the variable number tandem repeat (VNTR) polymorphism in the 3′ untranslated region (UTR) of the dopamine transporter gene in the child to increase understanding of gene-environment interactions involving early parenting. Participants were part of a 9-year longitudinal study of 4–6-year-old children who met criteria for attention-deficit/hyperactivity disorder (ADHD) and demographically matched controls. Maternal parenting was observed during standard mother-child interactions in wave 1. The child’s conduct disorder (CD) symptoms 5–8 years later were measured using separate structured diagnostic interviews of the mother and youth. Controlling for ADHD symptoms and child disruptive behavior during the mother-child interaction, there was a significant inverse relation between levels of both positive and negative parenting at 4–6 years and the number of later CD symptoms, but primarily among children with two copies of the 9-repeat allele of the VNTR. The significant interaction with negative parenting was replicated in parent and youth reports of CD symptoms separately.

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“…Alcohol also affects other transmitter systems such as serotonergic and dopaminergic systems that are involved in the predisposition to, and reinforcement of, excessive alcohol consumption, respectively (Heinz and Goldman 2000). In contrast, the endogenous opioid system has been implicated in alcohol addiction as an anti-reward system and is upregulated in response to mesolimbic dopamine activity (Bazov et al 2013).…”

Section: Alcohol and The Human Brainmentioning

confidence: 99%

Using Autopsy Brain Tissue to Study Alcohol-Related Brain Damage in the Genomic Age

Sutherland

Sheedy

Kril

2013

Alcohol Clin Exp Res

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The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52).

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Genotype effects on neurodegeneration and neuroadaptation in monoaminergic neurotransmitter systems

Cited by 32 publications

References 65 publications

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

Interactions between early parenting and a polymorphism of the child's dopamine transporter gene in predicting future child conduct disorder symptoms.

Using Autopsy Brain Tissue to Study Alcohol-Related Brain Damage in the Genomic Age

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