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.

• Keywords
• adipokine, antipsychotic, lipid profile, methylazoxymethanol, schizophrenia,
• MeSH
• Antipsychotic Agents * therapeutic use   MeSH
• Haloperidol * toxicity   MeSH
• Rats MeSH
• Lipids MeSH
• Methylazoxymethanol Acetate toxicity   analogs & derivatives   MeSH
• Disease Models, Animal MeSH
• Olanzapine toxicity   MeSH
• Rats, Sprague-Dawley MeSH
• Pregnancy MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antipsychotic Agents * MeSH
• Haloperidol * MeSH
• Lipids MeSH
• methylazoxymethanol MeSH Browser
• Methylazoxymethanol Acetate MeSH
• Olanzapine 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.

• Keywords
• biocompatibility, conducting polymer, neurogenesis, polypyrrole, stem cells,
• MeSH
• Cell Differentiation drug effects   genetics   MeSH
• Cell Line MeSH
• Embryoid Bodies cytology   drug effects   MeSH
• Gene Expression drug effects   MeSH
• Molecular Structure MeSH
• Mouse Embryonic Stem Cells cytology   drug effects   metabolism   MeSH
• Mice MeSH
• Neural Stem Cells cytology   drug effects   metabolism   MeSH
• Neurogenesis drug effects   genetics   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Polymers chemistry   pharmacology   MeSH
• Pyrroles chemistry   pharmacology   MeSH
• PAX6 Transcription Factor genetics   MeSH
• Basic Helix-Loop-Helix Transcription Factors genetics   MeSH
• SOXB1 Transcription Factors genetics   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Ascl1 protein, mouse MeSH Browser
• Polymers MeSH
• polypyrrole MeSH Browser
• Pyrroles MeSH
• PAX6 Transcription Factor MeSH
• Basic Helix-Loop-Helix Transcription Factors MeSH
• SOXB1 Transcription Factors MeSH