TY - JOUR
T1 - Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum
AU - Goncalves, Tassia M.
AU - Southey, Bruce R.
AU - Rodriguez-Zas, Sandra L.
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
KW - gene networks
KW - overactive line
KW - psychostimulant
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85060222706&partnerID=8YFLogxK
U2 - 10.1177/1177932218815152
DO - 10.1177/1177932218815152
M3 - Article
AN - SCOPUS:85060222706
SN - 1177-9322
VL - 12
JO - Bioinformatics and Biology Insights
JF - Bioinformatics and Biology Insights
ER -