Farmakoterapie v těhotenství; vliv na homeostázu monoaminů v placentě
For accurate fetal programming, proper levels of monoamines (serotonin, noradrenaline and dopamine) are of crucial importance and their concentrations must be tightly regulated in the feto-placental unit. Different types of transporters have been described in the placenta, mediating monoamine uptake, specifically: serotonin transporter, noradrenaline transporter and organic cation transporter 3. During pregnancy, monoamine regulation is prone to external insults such as inflammation, malnutrition, stress and use of medication. Pharmacotherapy in pregnancy is unavoidable in certain medical conditions; nonetheless, epidemiological studies have reported neurodevelopmental and psychiatric alterations with prenatal use of antiretrovirals, antiepileptics, antipsychotics and antidiabetics. Thus, the aim of this project is to determine the potential of these drugs to interact with placental monoamine homeostasis. Using ex vivo uptake assays in membrane vesicles isolated from human term placenta and in situ perfusion of rat placenta, we will investigate the effect of selected drugs on the function of placental monoamine transporters. Subsequently, the identified inhibitors will be subjected to long-term treatment studies in rats where the effect of chronic drug exposure on gene/protein expression of monoamine transporters will be assayed. The outcomes of this project could help identify mechanisms by which prenatal drug use affects fetal programming of mental disorders.
Číslo:
GAUK358821
Období:
01.01.2021 - 31.12.2023
Poskytovatel:
Univerzita Karlova - Grantová agentura UK
Hlavní řešitel:
Váchalová Veronika Mgr. - Farmaceutická fakulta v Hradci Králové
Celkový objem financí:
887 000,00 Kč
Interní řešitelé
Hlavní řešitel: Mgr. Veronika Váchalová
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Rona Karahoda, Ph.D.
- Univerzita Karlova,
Spoluřešitel: Mgr. Hana Horáčková, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Fiona Kumnova
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Rona Karahoda, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Školitel: prof. PharmDr. František Štaud, Ph.D.
- Univerzita Karlova,