Basic information

Investigator: Mgr. Grygoriy Tsenov, MSc., Ph.D.
Main recipient: Institute of Endocrinology Prague
Co-recipient: National Institute of Mental Health (NIMH)
Research period: 1/3/2023 - 31/12/2025
Total budget: 13,383,000 CZK
NIMH budget: 6,123,000 CZK
Supported by: Czech Science Foundation (GAČR)

Annotation

Neuroactive steroids (NAS) modulate the GABAercic and glutamatergic receptors and represent an attractive topic in pharmacology. The levels of neuroprotective NAS are pronouncedly elevated in the perinatal period. Moreover, an imbalance between excitation and inhibition are common in ischemic-hypoxic stress of neonates. Our previous data indicated that besides endogenous but toxic pregnanolone sulfate, some of its synthetic derivatives such as pregnenolone glutamate, hemisuccinate, and hemipimelate are non-toxic neuroprotective substances (modulating both GABAergic and glutamatergic receptors). However, they may be metabolized after i.p. application. Therefore, in this project, we focused on the mechanism of neuroprotective effects of conjugated 3α5β NAS in the context of their metabolism and transport from periphery into the CNS using a rat model and GC-MS/MS based steroidomic analysis. We will also investigate whether these neuroprotective effects involve the interplay between activities of NMDAR, phospholipase A2 and metabolism of arachidonic acid.