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Effects of allopregnanolon on motor functions of young laboratory rat.
Krejčí, Lukáš ; Mareš, Pavel (advisor) ; Valeš, Karel (referee)
Allopregnanolone is a typical representative of neurosteroids. It can be formed by de novo synthesis directly in the CNS or as a metabolite of progesterone. It is an allosteric modulator of GABAA receptors, due to which it has anxiolytic, sedative and anticonvulsant effects. This work investigates the effect of allopregnanolone (ALLO) on the locomotor skills of laboratory rat pups. The results will serve as a reference study for the work of Tereza Košťálová (2020), who investigated the newly discovered neuroactive steroid pregnanolone pyroglutamate (PPG). This exogenous steroid, synthesized at the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic (IOCB PRAGUE), offers potential use in the treatment of epilepsy. Our goal was to perform the same battery of motor tests after the application of allopregnanolone as a comparison, to what extent and in what way these two substances acutely affect the motor performance of the rat pup. The theoretical part of the thesis describes the physiological mechanisms of neurosteroids in the human body and their potential in the treatment of serious diseases, especially epilepsy. Next, the ontogenetic development of the rat's motor skills is described and compared to humans. The methodology describes the selection and...
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Neurosteroid effects on neuronal network activity in vitro.
Strnadová, Lenka ; Smejkalová, Terézia (advisor) ; Heleš, Mário (referee)
GABA receptors type A (GABAAR) are ligand-gated ion channels permeable for chloride anions. In the mammalian brain they mediate most of the inhibitory transmission. Moreover, the dysfunctions of the GABA-mediated system result in many neurological disorders, including epilepsy, anxiety and depression. Neurosteroids are cholesterol metabolites interacting with a variety of membrane receptors and have a direct effect on neuronal excitability. The neurosteroids allo-pregnanolone (allo-PA) and pregnanolone (PA) are potent positive modulators of the GABAAR. The goal of this work is to establish a newly constructed application system and a calcium imaging method using the GCaMP sensor to examine the effects of PA on the activity of primary hippocampal cultures. In this work we validate the application system and test the GCaMP calcium sensor in vitro. Application of PA inhibited the spontaneous calcium peaks, which agrees with its known actions on the GABAAR. We discovered that the neurosteroid inhibitory effect on the neuronal network activity changes after repeated applications. The results suggest that there might be some compensatory actions on the GABAAR level during prolonged or repeated exposition to PA. Key words: GABAAR; neurosteroid; pregnanolone; allopregnanolone; calcium; GCaMP; inhibition
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