Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum

The psychostimulant amphetamine can be prescribed to ameliorate the symptoms of narcolepsy, attention-deficit hyperactivity disorder and to facilitate weight loss. This stimulant can also have negative effects including toxicity and addiction risk. The impact of amphetamine on gene networks is parti...

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Main Authors: Tassia M Goncalves, Bruce R Southey, Sandra L Rodriguez-Zas
Format: Article
Language:English
Published: SAGE Publishing 2018-12-01
Series:Bioinformatics and Biology Insights
Online Access:https://doi.org/10.1177/1177932218815152
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author Tassia M Goncalves
Bruce R Southey
Sandra L Rodriguez-Zas
author_facet Tassia M Goncalves
Bruce R Southey
Sandra L Rodriguez-Zas
author_sort Tassia M Goncalves
collection DOAJ
description The psychostimulant amphetamine can be prescribed to ameliorate the symptoms of narcolepsy, attention-deficit hyperactivity disorder and to facilitate weight loss. This stimulant can also have negative effects including toxicity and addiction risk. The impact of amphetamine on gene networks is partially understood and this study addresses this gap in consideration of the physical activity. The striata of mice exposed to either amphetamine or saline treatment were compared in a mouse line selected for home cage physical overactivity, a phenotype that can be mitigated with amphetamine, and in a contemporary control line using RNA-seq. Genes presenting opposite expression patterns between treatments across lines included a pseudogene of coiled-coil-helix-coiled-coil-helix domain containing 2 gene (Chchd2), ribonuclease P RNA component H1 (Rpph1), short stature homeobox 2 (Shox2), transient receptor potential melastatin 6 (Trpm6), and tumor necrosis factor receptor superfamily, member 9 (Tnfrsf9). Genes presenting consistent treatment patterns across lines, albeit at different levels of significance included cholecystokinin (Cck), vasoactive intestinal polypeptide (Vip), arginine vasopressin (Avp), oxytocin/neurophysin (Oxt), thyrotropin releasing hormone (Trh), neurotensin (Nts), angiotensinogen (Agt), galanin (Gal), prolactin receptor (Prlr), and calcitonin receptor (Calcr). Potassium inwardly rectifying channel, subfamily J, member 6 (Kcnj6), and retinoic acid-related (RAR)-related orphan receptor alpha (Rora) were similarly differentially expressed between treatments across lines. Functional categories enriched among the genes presenting line-dependent amphetamine effect included genes coding for neuropeptides and associated with memory and neuroplasticity and synaptic signaling, energy, and redox processes. A line-dependent association between amphetamine exposure and the synaptic signaling genes neurogranin (Nrgn) and synaptic membrane exocytosis 1(Rims1) was highlighted in the gene networks. Our findings advance the understanding of molecular players and networks affected by amphetamine in support of the development of activity-targeted therapies that may capitalize on the benefits of this psychostimulant.
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spelling doaj.art-98e28d6cf44e42e3bcc1dad4d1dc0b922022-12-22T03:04:48ZengSAGE PublishingBioinformatics and Biology Insights1177-93222018-12-011210.1177/1177932218815152Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse StriatumTassia M Goncalves0Bruce R Southey1Sandra L Rodriguez-Zas2Department of Animal Sciences, University of Illinois at Urbana–Champaign, Urbana, IL, USADepartment of Animal Sciences, University of Illinois at Urbana–Champaign, Urbana, IL, USADepartment of Statistics, University of Illinois at Urbana–Champaign, Urbana, IL, USAThe psychostimulant amphetamine can be prescribed to ameliorate the symptoms of narcolepsy, attention-deficit hyperactivity disorder and to facilitate weight loss. This stimulant can also have negative effects including toxicity and addiction risk. The impact of amphetamine on gene networks is partially understood and this study addresses this gap in consideration of the physical activity. The striata of mice exposed to either amphetamine or saline treatment were compared in a mouse line selected for home cage physical overactivity, a phenotype that can be mitigated with amphetamine, and in a contemporary control line using RNA-seq. Genes presenting opposite expression patterns between treatments across lines included a pseudogene of coiled-coil-helix-coiled-coil-helix domain containing 2 gene (Chchd2), ribonuclease P RNA component H1 (Rpph1), short stature homeobox 2 (Shox2), transient receptor potential melastatin 6 (Trpm6), and tumor necrosis factor receptor superfamily, member 9 (Tnfrsf9). Genes presenting consistent treatment patterns across lines, albeit at different levels of significance included cholecystokinin (Cck), vasoactive intestinal polypeptide (Vip), arginine vasopressin (Avp), oxytocin/neurophysin (Oxt), thyrotropin releasing hormone (Trh), neurotensin (Nts), angiotensinogen (Agt), galanin (Gal), prolactin receptor (Prlr), and calcitonin receptor (Calcr). Potassium inwardly rectifying channel, subfamily J, member 6 (Kcnj6), and retinoic acid-related (RAR)-related orphan receptor alpha (Rora) were similarly differentially expressed between treatments across lines. Functional categories enriched among the genes presenting line-dependent amphetamine effect included genes coding for neuropeptides and associated with memory and neuroplasticity and synaptic signaling, energy, and redox processes. A line-dependent association between amphetamine exposure and the synaptic signaling genes neurogranin (Nrgn) and synaptic membrane exocytosis 1(Rims1) was highlighted in the gene networks. Our findings advance the understanding of molecular players and networks affected by amphetamine in support of the development of activity-targeted therapies that may capitalize on the benefits of this psychostimulant.https://doi.org/10.1177/1177932218815152
spellingShingle Tassia M Goncalves
Bruce R Southey
Sandra L Rodriguez-Zas
Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
Bioinformatics and Biology Insights
title Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
title_full Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
title_fullStr Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
title_full_unstemmed Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
title_short Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
title_sort interplay between amphetamine and activity level in gene networks of the mouse striatum
url https://doi.org/10.1177/1177932218815152
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