title: The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus.
abstract: Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity. The aim of the current study was to investigate the ability of the AMPA receptor potentiator Org 26576 to modulate BDNF expression in selected brain regions under basal conditions or in response to an acute swim stress. Rats subjected to a single intraperitoneal injection with Org 26576 (10mg/kg) or saline were exposed to a swim stress session (5 min) and sacrificed 15 min after the end of stress. Real-time PCR assay was used to determine changes in BDNF transcription in different brain regions. Total BDNF mRNA levels were significantly increased in the hippocampus of animals exposed to the combination of Org 26576 and stress whereas, in prefrontal and frontal cortices, BDNF mRNA levels were modulated by the acute stress, independently from drug treatment. The analysis of BDNF transcripts in the hippocampus revealed a major contribution of exons I and IV. Our results suggest that AMPA receptor potentiation by Org 26576 exerts a positive modulatory influence on BDNF expression during ongoing neuronal activity. Given that these mechanisms are critical for neuronal plasticity, we hypothesized that such changes may facilitate learning/coping mechanisms associated with a mild stressful experience.
authors.affiliation: Center of Neuropharmacology, Department of Pharmacological Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
authors.forename: Francesca
authors.initials: F
authors.lastname: Calabrese
authors.forename: Alessia
authors.initials: A
authors.lastname: Luoni
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shahid
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005091:Exons; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D013550:Swimming / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C545643:Org 26576; D020033:Protein Isoforms; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid