Publications by authors named "Eda Stark"
Article Synopsis
- Preclinical and clinical studies indicate that activating muscarinic acetylcholine receptors (mAChRs) may help treat schizophrenia and Alzheimer's, particularly through the drug xanomeline, which targets M1 and M4 receptors.
- The research compared xanomeline's effects to those of selective M1 and M4 activators on important signaling pathways in various brain regions of mice and assessed its impact on brain activity in rats.
- Findings revealed that xanomeline's effects align with M1 and M4 activation but vary across brain areas, suggesting a complex interaction that may underlie its clinical effectiveness, especially at lower doses favoring M4 receptor activation.
Abnormal hippocampal activity has been linked to impaired cognitive performance in Alzheimer's disease and schizophrenia, leading to a hypothesis that normalization of this activity may be therapeutically beneficial. Our work suggests that one approach for hippocampal normalization may be through activation of the M4 muscarinic acetylcholine receptor. We used a brain penetrant M4 muscarinic acetylcholine receptor selective activator, PT-3763, to show dose-dependent attenuation of field potentials in Schaffer collateral (CA3-CA1) and recurrent associational connections (CA3-CA3) ex vivo in hippocampal slices.
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- Hippocampal networks are vulnerable to dysfunction in various neurodegenerative diseases like Alzheimer's and disorders such as schizophrenia, with CA1 being a key output area.
- This study examines the roles of M1 and M4 muscarinic receptors in modulating glutamatergic synaptic transmission in CA1, revealing that M1 activation boosts neuronal activity while M4 activation suppresses glutamate release in the SC pathway.
- The results suggest potential therapeutic mechanisms for addressing cognitive impairments linked to neurodegenerative conditions, which aligns with positive outcomes from using xanomeline, an M1/M4 receptor agonist, in patients with Alzheimer's and schizophrenia.