Basic information

Investigator: Mgr. Lenka Kletečková, Ph.D.
Main recipient: Institute of Endocrinology, Prague
Co-recipient: National Institute of Mental Health (NUDZ)
Research period: 01/05/2025 - 31/12/2025
Total budget: 6,983,000 CZK
NIMH budget: 3,492,000 CZK
Supported by: AZV (Czech Health Research Council)

 

 

Annotation

Inflammatory signaling in nervous tissue serves as a physiological protective response in the presence of infections and injuries to the nervous system. However, neuroinflammation is a common characteristic in various neurological diseases (e.g., neurodegenerative diseases, traumatic brain injury, stroke, and psychiatric disorders), where it plays a significant role as a pathological contributor. Understanding the neuroinflammatory response under physiological and pathophysiological conditions is crucial for developing new therapeutic targets. Current research undeniably highlights the important role of endogenous neurosteroids in regulating the complex processes of neuroinflammation, which can significantly contribute to mitigating inflammatory responses. In the proposed project, we expect to demonstrate the antiinflammatory properties of selected synthetic neuroactive steroids, pregnanolone glutamate and pregnanolone pyroglutamate, which are analogs of naturally occurring neurosteroids. We will administer these neuroactive steroids in an animal model of neuroinflammation induced by lipopolysaccharide (LPS) and compare their effects with an FDA-approved neuroactive steroid (an analog of allopregnanolone). The project will employ a variety of methodological approaches to yield its results. We will focus on characteristic immunohistological markers of inflammation, such as reactive astrogliosis, neurodegeneration, and microglial activation. Additionally, we will analyze potential changes in the steroid metabolome using mass spectrometry from brain tissue and blood plasma. Simultaneously, we will monitor levels of inflammatory markers (TNF-?, IL-6, and IL-1ß) in the brain tissue in the same structures where we will analyze changes in steroid metabolism. The project is supported by positive preliminary results from previous collaborations and represents targeted medical research focused on finding new therapeutic approaches in the field of neurological disorders.