Az immobilizációs stressz és a sertindol hatása az APP, MAPK-1 és β-AKTIN gének kifejezo{combining double acute accent}désére patkányagyban

János Kálmán, M. Pákáski, Szabina Szucs, Sára Kálḿan, Örsike Fazekas, Petra Sántha, Gyula Szabó, Z. Janka, J. Kálmán

Research output: Article

2 Citations (Scopus)

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 β-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], β-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 β-actin (p <0.01), MAPK-1 and APP (p <0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in β-actin, MAPK-1 and APP expression (p <0.05). Ours is the first report about CIS induced β-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.

Original languageHungarian
Pages (from-to)394-400
Number of pages7
JournalIdeggyógyászati szemle
Volume65
Issue number11-12
Publication statusPublished - nov. 30 2012

Fingerprint

Amyloid beta-Protein Precursor
Mitogen-Activated Protein Kinase 1
Immobilization
Actins
Alzheimer Disease
Brain
Genes
Antipsychotic Agents
Actin Depolymerizing Factors
Behavioral Symptoms
Messenger RNA
Brain-Derived Neurotrophic Factor
Neuroprotective Agents
Synapses
Atrophy
Dementia
Hydrocortisone
sertindole
Wistar Rats
Real-Time Polymerase Chain Reaction

Keywords

  • β-actin
  • Alzheimer's disease
  • Amyloid precursor protein
  • Chronic immobilization stress
  • Hippocampus
  • Mitogen activated protein kinase-1
  • Sertindole

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Az immobilizációs stressz és a sertindol hatása az APP, MAPK-1 és β-AKTIN gének kifejezo{combining double acute accent}désére patkányagyban. / Kálmán, János; Pákáski, M.; Szucs, Szabina; Kálḿan, Sára; Fazekas, Örsike; Sántha, Petra; Szabó, Gyula; Janka, Z.; Kálmán, J.

In: Ideggyógyászati szemle, Vol. 65, No. 11-12, 30.11.2012, p. 394-400.

Research output: Article

Kálmán, János ; Pákáski, M. ; Szucs, Szabina ; Kálḿan, Sára ; Fazekas, Örsike ; Sántha, Petra ; Szabó, Gyula ; Janka, Z. ; Kálmán, J. / Az immobilizációs stressz és a sertindol hatása az APP, MAPK-1 és β-AKTIN gének kifejezo{combining double acute accent}désére patkányagyban. In: Ideggyógyászati szemle. 2012 ; Vol. 65, No. 11-12. pp. 394-400.
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AU - Pákáski, M.

AU - Szucs, Szabina

AU - Kálḿan, Sára

AU - Fazekas, Örsike

AU - Sántha, Petra

AU - Szabó, Gyula

AU - Janka, Z.

AU - Kálmán, J.

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