title: Modulation of BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition and in response to acute stress.
abstract: It is known that long-term treatment with antipsychotic drugs (APDs) produces neuroadaptive changes through the modulation of different proteins that, by enhancing neuronal plasticity and cellular resiliency, may improve core disease symptoms. The aim of this study was to investigate the ability of chronic treatment with the novel antipsychotic lurasidone to modulate BDNF expression in hippocampus and prefrontal cortex, under basal conditions or in response to an acute stress, a major precipitating element in psychiatric disorders. By means of real-time PCR, we found that (1) chronic lurasidone treatment increases total BDNF mRNA levels in rat prefrontal cortex and, to less extent, in hippocampus; (2) the modulation of BDNF mRNA levels in response to acute swim stress in lurasidone-treated rats was markedly potentiated in hippocampus, and to less extent in prefrontal cortex, through the selective regulation of different neurotrophin isoforms. The increase of BDNF mRNA levels in prefrontal cortex was paralleled by an enhancement of mature BDNF protein levels. In conclusion, repeated exposure to lurasidone regulates BDNF expression, through a finely tuned modulation of its transcripts. This effect may contribute to the amelioration of functions, such as cognition, closely associated with neuronal plasticity, which are deteriorated in schizophrenia patients.
authors.affiliation: Center of Neuropharmacology, Department of Pharmacological Sciences, Università degli Studi di Milano, 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: Francesca
authors.initials: F
authors.lastname: Bolis
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
mesh_terms: D000208:Acute Disease; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D054833:Isoindoles / Q000008:administration & dosage*; D000069056:Lurasidone Hydrochloride; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism*; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D054833:Isoindoles; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride