Search

Copyright of Dimensión Empresarial is the property of Universidad Autonoma del Caribe, Departamento del Atlantico and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neuronal and network-level hyperexcitability is commonly associated with increased levels of amyloid-β (Aβ) and contribute to cognitive deficits associated with Alzheimer's disease (AD). However, the mechanistic complexity underlying the selective loss of basal fore-brain cholinergic neurons (BFCNs), a well-recognized characteristic of AD, remains poorly understood. In this study, we tested the hypothesis that the oligomeric form of amyloid-β (oAβ42), interacting with α7-containing nicotinic acetylcholine receptor (nAChR) subtypes, leads to subnucleus-specific alterations in BFCN excitability and impaired cognition. We used single-channel electrophysiology to show that oAβ42 activates both homomeric aα- and heteromeric α7β2-nAChR subtypes while preferentially enhancing α7β2-nAChR open-dwell times. Organotypic slice cultures were prepared from male and female ChAT-EGFP mice, and current-clamp recordings obtained from BFCNs chronically exposed to pathophysiologically relevant level of oAβ42 showed enhanced neuronal intrinsic excitability and action potential firing rates. These resulted from a reduction in action potential afterhyperpolarization and alterations in the maximal rates of voltage change during spike depolarization and repolarization. These effects were observed in BFCNs from the medial septum diagonal band and horizontal diagonal band, but not the nucleus basalis. Last, aged male and female APP/ PS1 transgenic mice, genetically null for the β2 nAChR subunit gene, showed improved spatial reference memory compared with APP/PS1 aged-matched littermates. Combined, these data provide a molecular mechanism supporting a role for α7β2-nAChR in mediating the effects of oAβ42 on excitability of specific populations of cholinergic neurons and provide a framework for understanding the role of α7β2-nAChR in oAβ42-induced cognitive decline. [ABSTRACT FROM AUTHOR]

The novel Coronavirus (COVID-19) is a highly contagious viral illness that has caused the most significant global health crisis in recent human history. Individuals experiencing homelessness represent one of the more vulnerable populations for COVID-19 infection and morbidity. Amongst individuals experiencing homelessness in Phoenix, a student-led interprofessional organization called Street Medicine Phoenix (SMP) sought to both reduce the risk of COVID-19 transmission and morbidity/mortality related to infection. Through collaborations with the Maricopa County Department of Public Health and various community organizations, SMP developed a format for street-based vaccination clinics. SMP deployed these clinics on numerous occasions to the streets directly surrounding the community homeless shelter, allowing SMP to vaccinate individuals directly in their encampments. Through SMP's efforts starting in February 2021, 400 individuals experiencing homelessness have received at least one COVID-19 vaccine. Challenges encountered included low health literacy, lack of established rapport and trust, low vaccine confidence, difficulty verifying patients' vaccination status, difficulty obtaining sufficient information from patients to create a record in the Arizona State Immunization Information System (ASIIS), monitoring patients post-vaccination, transporting vaccine supplies from encampment to encampment, and lack of patient awareness of the mobile vaccine clinic services. Despite challenges, SMP's outreach efforts have demonstrated the feasibility and importance of mobile public health services to reach homeless encampments, particularly mobile vaccination clinics in response to disease outbreaks, and the necessity of strategic partnerships with community agencies to effectively meet the needs of underserved populations.

Neuronal and network-level hyperexcitability is commonly associated with increased levels of amyloid-β (Aβ) and contribute to cognitive deficits associated with Alzheimer's disease (AD). However, the mechanistic complexity underlying the selective loss of basal forebrain cholinergic neurons (BFCNs), a well-recognized characteristic of AD, remains poorly understood. In this study, we tested the hypothesis that the oligomeric form of amyloid-β (oAβ 42 ), interacting with α7-containing nicotinic acetylcholine receptor (nAChR) subtypes, leads to subnucleus-specific alterations in BFCN excitability and impaired cognition. We used single-channel electrophysiology to show that oAβ 42 activates both homomeric α7- and heteromeric α7β2-nAChR subtypes while preferentially enhancing α7β2-nAChR open-dwell times. Organotypic slice cultures were prepared from male and female ChAT-EGFP mice, and current-clamp recordings obtained from BFCNs chronically exposed to pathophysiologically relevant level of oAβ 42 showed enhanced neuronal intrinsic excitability and action potential firing rates. These resulted from a reduction in action potential afterhyperpolarization and alterations in the maximal rates of voltage change during spike depolarization and repolarization. These effects were observed in BFCNs from the medial septum diagonal band and horizontal diagonal band, but not the nucleus basalis. Last, aged male and female APP/PS1 transgenic mice, genetically null for the β2 nAChR subunit gene, showed improved spatial reference memory compared with APP/PS1 aged-matched littermates. Combined, these data provide a molecular mechanism supporting a role for α7β2-nAChR in mediating the effects of oAβ 42 on excitability of specific populations of cholinergic neurons and provide a framework for understanding the role of α7β2-nAChR in oAβ 42 -induced cognitive decline., Competing Interests: The authors declare no competing financial interests., (Copyright © 2021 the authors.)