PMID- 29182611 OWN - NLM STAT- MEDLINE DCOM- 20180706 LR - 20180706 IS - 1689-0035 (Electronic) IS - 0065-1400 (Linking) VI - 77 IP - 3 DP - 2017 TI - The differential effects of neuroleptic drugs and PACAP on the expression of BDNF mRNA and protein in a human glioblastoma cell line. PG - 205-213 AB - Despite numerous studies, the molecular mechanisms underpinning the action of antipsychotic drugs remain not fully understood. It has been suggested that, in addition to the modulation of monoaminergic neurotransmission, antipsychotic drugs can also affect the expression of neurotrophic factors in the brain. The present study examines the effects of a first-generation neuroleptic drug (FGA; haloperidol) and two second-generation neuroleptic drugs (SGAs; olanzapine and amisulpride) on the expression and levels of brain-derived neurotrophic factor (BDNF) in an astrocyte-like T98G glioblastoma cell line. The effects of these drugs were compared to the action of PACAP38, a neuropeptide with well-known BDNF-mediated neuroprotective effects. The tested neuroleptics differentially regulated the mRNA expression and protein level of BDNF depending on concentration and incubation time. Real-time PCR analysis demonstrates that, of the three tested neuroleptics, both haloperidol and olanzapine at a concentration of 5 microM (but not at 20 microM) increased BDNF mRNA expression with similar efficacy after 72-hour incubation. In order to confirm the observed changes in the mRNA expression of BDNF, a protein expression assay was performed. The exposure of cells to 5 muM olanzapine alone for 72 hours increased BDNF concentration in the culture medium by 29%. Additionally, PACAP significantly up-regulated BDNF mRNA expression in T98G cells and the obtained results correlated positively with the increased production of BDNF protein, 22% above control values. Our findings show that olanzapine, similarly to exogenous PACAP38, increased BDNF mRNA expression and protein release, which can contribute to its neuroprotective mechanism of action in the cells of non-neuronal origin. The results of the paper show that olanzapine, similarly to exogenous PACAP38, increased BDNF mRNA expression and protein release, which can contribute to its neuroprotective mechanism of action in the cells of nonneuronal origin. The results of the present paper confirm the findings that BDNF may represent the key target for olanzapine and PACAP. FAU - Jozwiak-Bebenista, Marta AU - Jozwiak-Bebenista M AD - Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology and Toxicology, Medical University of Lodz, Poland; marta.jozwiak-bebenista@umed.lodz.pl. FAU - Jasinska-Stroschein, Magdalena AU - Jasinska-Stroschein M AD - Department of Biopharmacy, Medical University of Lodz, Poland. FAU - Kowalczyk, Edward AU - Kowalczyk E AD - Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology and Toxicology, Medical University of Lodz, Poland. LA - eng PT - Journal Article PL - Poland TA - Acta Neurobiol Exp (Wars) JT - Acta neurobiologiae experimentalis JID - 1246675 RN - 0 (Antipsychotic Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (RNA, Messenger) SB - IM MH - Analysis of Variance MH - Antipsychotic Agents/*pharmacology MH - Brain-Derived Neurotrophic Factor/*genetics/*metabolism MH - Cell Line, Tumor MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Glioblastoma/pathology MH - Humans MH - Pituitary Adenylate Cyclase-Activating Polypeptide/*pharmacology MH - RNA, Messenger/*metabolism MH - Time Factors EDAT- 2017/11/29 06:00 MHDA- 2018/07/07 06:00 CRDT- 2017/11/29 06:00 PHST- 2017/11/29 06:00 [entrez] PHST- 2017/11/29 06:00 [pubmed] PHST- 2018/07/07 06:00 [medline] AID - 7724 [pii] PST - ppublish SO - Acta Neurobiol Exp (Wars). 2017;77(3):205-213.