AIM: Widely used second-generation antipsychotics are associated with adverse metabolic effects, contributing to increased cardiovascular mortality. To develop strategies to prevent or treat adverse metabolic effects, preclinical models have a clear role in uncovering underlying molecular mechanisms. However, with few exceptions, preclinical studies have been performed in healthy animals, neglecting the contribution of dysmetabolic features inherent to psychotic disorders. METHODS: In this study, methylazoxymethanol acetate (MAM) was prenatally administered to pregnant Sprague-Dawley rats at gestational day 17 to induce a well-validated neurodevelopmental model of schizophrenia mimicking its assumed pathogenesis with persistent phenotype. Against this background, the dysmetabolic effects of acute treatment with olanzapine and haloperidol were examined in female rats. RESULTS: Prenatally MAM-exposed animals exhibited several metabolic features, including lipid disturbances. Half of the MAM rats exposed to olanzapine had pronounced serum lipid profile alteration compared to non-MAM controls, interpreted as a reflection of a delicate MAM-induced metabolic balance disrupted by olanzapine. In accordance with the drugs' clinical metabolic profiles, olanzapine-associated dysmetabolic effects were more pronounced than haloperidol-associated dysmetabolic effects in non-MAM rats and rats exposed to MAM. CONCLUSION: Our results demonstrate metabolic vulnerability in female prenatally MAM-exposed rats, indicating that findings from healthy animals likely provide an underestimated impression of metabolic dysfunction associated with antipsychotics. In the context of metabolic disturbances, neurodevelopmental models possess a relevant background, and the search for adequate animal models should receive more attention within the field of experimental psychopharmacology.

• Klíčová slova
• adipokine, antipsychotic, lipid profile, methylazoxymethanol, schizophrenia,
• MeSH
• antipsychotika * terapeutické užití   MeSH
• haloperidol * toxicita   MeSH
• krysa rodu Rattus MeSH
• lipidy MeSH
• methylazoxymethanolacetát toxicita   analogy a deriváty   MeSH
• modely nemocí na zvířatech MeSH
• olanzapin toxicita   MeSH
• potkani Sprague-Dawley MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antipsychotika * MeSH
• haloperidol * MeSH
• lipidy MeSH
• methylazoxymethanol MeSH Prohlížeč
• methylazoxymethanolacetát MeSH
• olanzapin MeSH

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

• Klíčová slova
• biocompatibility, conducting polymer, neurogenesis, polypyrrole, stem cells,
• MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• buněčné linie MeSH
• embryoidní tělíska cytologie   účinky léků   MeSH
• exprese genu účinky léků   MeSH
• molekulární struktura MeSH
• myší embryonální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• nervové kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• neurogeneze účinky léků   genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• polymery chemie   farmakologie   MeSH
• pyrroly chemie   farmakologie   MeSH
• transkripční faktor PAX6 genetika   MeSH
• transkripční faktory bHLH genetika   MeSH
• transkripční faktory SOXB1 genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ascl1 protein, mouse MeSH Prohlížeč
• polymery MeSH
• polypyrrole MeSH Prohlížeč
• pyrroly MeSH
• transkripční faktor PAX6 MeSH
• transkripční faktory bHLH MeSH
• transkripční faktory SOXB1 MeSH