title: [The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and beta-actin genes in rat brain].
abstract: Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer's disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations--also affecting the metabolism of beta-actin--can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], beta-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n = 16), CIS (n = 10), 10 mg/kg sertindole (n = 5) and 10 mg/kg sertindole + CIS (n = 4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal beta-actin (p < 0.01), MAPK-1 and APP (p < 0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in beta-actin, MAPK-1 and APP expression (p < 0.05). Ours is the first report about CIS induced beta-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.
authors.affiliation: Szegedi Tudományegyetem, Pszichiátriai Klinika, Alzheimer-kór Kutatócsoport, Szeged. kalmanjan@yahoo.com
authors.forename: János
authors.initials: J
authors.lastname: Kállmán
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.forename: Szabina
authors.initials: S
authors.lastname: Szucs
authors.forename: Sára
authors.initials: S
authors.lastname: Kálmán
authors.forename: Orsike
authors.initials: O
authors.lastname: Fazekas
authors.forename: Petra
authors.initials: P
authors.lastname: Santha
authors.forename: Gyula
authors.initials: G
authors.lastname: Szabó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
mesh_terms: D000199:Actins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007103:Immobilization; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; C066304:sertindole