Basic information

Investigator: Mgr. Lenka Kletečková, Ph.D.
Main recipient: National Institute of Mental Health (NIMH)
Co-recipient: Institute of Physiology of the Czech Academy of Science
Research period:  1/5/2022 - 31/12/2025
Total budget: 6,842,000 CZK
NIMH budget: 5,417,000 CZK
Supported by: Czech Health Research Council (AZV ČR)

Annotation

Schizophrenia (SCZ) is a severe psychiatric disease affecting approximately 1% of the world population characterized by positive symptoms (delusion and hallucinations), negative symptoms (affective flattening, social withdrawal) and cognitive deficit. Although complete pathophysiology of SCZ is still unclear, a neurodevelopmental hypothesis of disease has been characterized and confirmed. Perinatal hypoxia-ischemia is a well-known epidemiological factor for SCZ, increasing the hazard ratio twofold, due to fundamental changes in glutamatergic as well as GABAergic system, dendritic outgrowth, synapse formation and maturation of neurons in this age. In the submitted project we will combine chronic intermittent hypoxia in the perinatal period of rat pups and induction of psychosis by application of MK-801 (antagonist of NMDA receptor) in their adolescence. The aims of this project are: 1) describe key alterations in the energetic brain metabolism after perinatal hypoxia and psychotic insult in adolescent age, 2) evaluate significant behavioral changes (prepulse inhibition, open field, “cognitive test”) in this animal model, 3) determine alteration in number of parvalbumin positive interneurons (prefrontal cortex, striatum, hippocampus) and hippocampal volume, 4) determine prophylactic effect of antipsychotic risperidone and SSRI citalopram (or their combination) on all these mentioned parameters. The submitted project will contribute to better understanding of pathophysiological changes in the affected brain and mainly contribute to better clinical practise in future.