Transcriptional profiling of SHR/NCrl prefrontal cortex shows hyperactivity-associated genes responsive to amphetamine challenge

Autor:	Aeree Sohn, Jong Hoon Ryu, Jae Hoon Cheong, I. J.I. dela Peña, I. dela Peña, Hee Jin Kim, Doug Hyun Han, Boong Nyun Kim, Chan Young Shin, J. B. de la Peña
Rok vydání:	2017
Předmět:	0301 basic medicine medicine.medical_specialty Microarray Biology medicine.disease Impulsivity PER2 03 medical and health sciences Behavioral Neuroscience 030104 developmental biology 0302 clinical medicine Endocrinology Neurodevelopmental disorder Neurology Internal medicine Gene expression Genetics medicine Circadian rhythm medicine.symptom Amphetamine Prefrontal cortex Neuroscience 030217 neurology & neurosurgery medicine.drug
Zdroj:	Genes, Brain and Behavior. 16:664-674
ISSN:	1601-1848
Popis:	Several studies suggest a strong genetic component of attention-deficit/hyperactivity disorder (ADHD), a complex neurodevelopmental disorder characterized by inappropriate levels of hyperactivity, impulsivity and inattention. Determining specific genetic risk variants for each symptom dimension of ADHD may aid in the identification of the biological risk factors of the disorder. In this study, we explored the potential genetic underpinnings of the hyperactive phenotype of ADHD. To this end, we examined differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of SHR/NCrl, an animal model of ADHD, compared with its genetic control, the Wistar Kyoto (WKY/NCrl) rat and the Wistar rat, strain used to represent the 'normal' heterogeneous population. Relative to WKY/NCrl and Wistar controls, SHR/NCrl showed hyperactivity in the open-field test. Treatment with the ADHD drug, amphetamine (AMPH) reduced hyperactivity in SHR/NCrl. Meanwhile, AMPH increased locomotor activity in WKY/NCrl and Wistar rats. Gene expression analysis found 21 common upregulated and 36 downregulated genes in the PFC of drug-naive SHR/NCrl when compared with WKY/NCrl and Wistar rats. Of these DEGs, expression levels of two genes, Atxn7 and Per2, which are involved in transcription and circadian rhythm, respectively, were downregulated following AMPH treatment in SHR/NCrl. Quantitative real-time-polymerase chain reaction analyses verified expression patterns of these genes in the PFC of drug-naive and AMPH-treated SHR/NCrl. The present findings indicate genetic risk variants that may be associated with the hyperactive phenotype in ADHD. Further studies are warranted to establish the roles of Atxn7 and Per2 in mediating hyperactivity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::bb2e4b28da7856f8cb7b59cf404bea54 https://doi.org/10.1111/gbb.12388 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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