Basic information

Investigator:  RNDr. Karel Valeš, PhD.
Main recipient: National Institute of Mental Health (NIMH)
Co-recipient: Institute of Physiology of the Czech Academy of Science
Research period: 1/1/2022 - 31/12/2024
Total budget: 11,692,000 CZK
NIMH budget: 6,891,000 CZK
Supported by: Czech Science Foundation (GAČR)

Annotation

Schizophrenia (SCZ) is a severe disease with a complex pathophysiology and a progressive course. According to our hypothesis, it is necessary to understand SCZ as a disease with neurodegenerative features. Increased oxidative stress markers, reduced number of mitochondria, and increased cytochrome c in SCZ patients suggest that brain metabolism may be impaired. Metabolic impairment would explain the progressive nature of SCZ and selective impairment of vulnerable parvalbumin-positive interneurons (PVIs) in SCZ patients. To model SCZ, we will use 22q11DS mice. To model repeated psychoses, we will repeatedly administer 0.3mg/kg of MK-801. To explore the effect of repeated psychosis-like episodes on subjects without associated genetic burden, we will use wild-type littermates. In both groups of mice, we will explore the respiratory rate, the function of the Krebs cycle and glycolysis enzymes, oxidative stress markers, numbers of PVIs and PV protein content, and metabolic markers. We will study PVIs metabolism using intravital imaging.