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Genetic variation i...
Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum.
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Simpson, Eleanor H (författare)
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- Morud, Julia, 1984 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Winiger, Vanessa (författare)
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Biezonski, Dominik (författare)
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Zhu, Judy P (författare)
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Bach, Mary Elizabeth (författare)
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Malleret, Gael (författare)
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Polan, H Jonathan (författare)
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Ng-Evans, Scott (författare)
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Phillips, Paul E M (författare)
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Kellendonk, Christoph (författare)
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Kandel, Eric R (författare)
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(creator_code:org_t)
- 2014-03-17
- 2014
- Engelska.
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Ingår i: Learning & memory (Cold Spring Harbor, N.Y.). - : Cold Spring Harbor Laboratory. - 1549-5485. ; 21:4, s. 205-14
- Relaterad länk:
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http://learnmem.cshl...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- A common genetic polymorphism that results in increased activity of the dopamine regulating enzyme COMT (the COMT Val(158) allele) has been found to associate with poorer cognitive performance and increased susceptibility to develop psychiatric disorders. It is generally assumed that this increase in COMT activity influences cognitive function and psychiatric disease risk by increasing dopamine turnover in cortical synapses, though this cannot be directly measured in humans. Here we explore a novel transgenic mouse model of increased COMT activity, equivalent to the relative increase in activity observed with the human COMT Val(158) allele. By performing an extensive battery of behavioral tests, we found that COMT overexpressing mice (COMT-OE mice) exhibit cognitive deficits selectively in the domains that are affected by the COMT Val(158) allele, stimulus-response learning and working memory, functionally validating our model of increased COMT activity. Although we detected no changes in the level of markers for dopamine synthesis and dopamine transport, we found that COMT-OE mice display an increase in dopamine release capacity in the striatum. This result suggests that increased COMT activity may not only affect dopamine signaling by enhancing synaptic clearance in the cortex, but may also cause changes in presynaptic dopamine function in the striatum. These changes may underlie the behavioral deficits observed in the mice and might also play a role in the cognitive deficits and increased psychiatric disease risk associated with genetic variation in COMT activity in humans.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Animals
- Catechol O-Methyltransferase
- genetics
- metabolism
- Cognition
- physiology
- Compulsive Behavior
- genetics
- metabolism
- Corpus Striatum
- metabolism
- Dopamine
- metabolism
- Dopamine Plasma Membrane Transport Proteins
- metabolism
- Impulsive Behavior
- Learning
- physiology
- Learning Disorders
- genetics
- metabolism
- Male
- Memory Disorders
- genetics
- metabolism
- Memory
- Short-Term
- physiology
- Mice
- Mice
- Inbred C57BL
- Mice
- Transgenic
- Models
- Animal
- Motor Activity
- genetics
- physiology
- Neuropsychological Tests
- Polymorphism
- Genetic
- Prosencephalon
- metabolism
- Tyrosine 3-Monooxygenase
- metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Simpson, Eleanor ...
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Morud, Julia, 19 ...
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Winiger, Vanessa
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Biezonski, Domin ...
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Zhu, Judy P
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Bach, Mary Eliza ...
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visa fler...
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Malleret, Gael
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Polan, H Jonatha ...
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Ng-Evans, Scott
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Phillips, Paul E ...
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Kellendonk, Chri ...
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Kandel, Eric R
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Learning & memor ...
- Av lärosätet
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Göteborgs universitet