Retinal Ganglion Cells Functional Changes in a Mouse Model of Alzheimer’s Disease Are Linked with Neurotransmitter Alterations
Autor: | Felipe Bello, Max Chacón, Gaganashree Shivashankar, Claudio Hetz, Monica L. Acosta, Claudia Duran-Aniotz, Joaquín Araya-Arriagada, Adrian G. Palacios, David Neira, Maria-Jose Escobar |
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Rok vydání: | 2021 |
Předmět: |
Male
Retinal Ganglion Cells 0301 basic medicine genetic structures Glutamic Acid Mice Transgenic Biology Retinal ganglion Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurochemical Alzheimer Disease medicine Animals Dementia Neurotransmitter Ganglion cell layer gamma-Aminobutyric Acid Neurotransmitter Agents Retina General Neuroscience Age Factors Glutamate receptor General Medicine medicine.disease Disease Models Animal Psychiatry and Mental health Clinical Psychology 030104 developmental biology medicine.anatomical_structure chemistry Female sense organs Geriatrics and Gerontology Hypoactivity Neuroscience Photic Stimulation 030217 neurology & neurosurgery |
Zdroj: | Journal of Alzheimer's Disease. 82:S5-S18 |
ISSN: | 1875-8908 1387-2877 |
Popis: | Background: Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide. This neurodegenerative syndrome affects cognition, memory, behavior, and the visual system, particularly the retina. Objective: This work aims to determine whether the 5xFAD mouse, a transgenic model of AD, displays changes in the function of retinal ganglion cells (RGCs) and if those alterations are correlated with changes in the expression of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters. Methods: In young (2–3-month-old) and adult (6-7-month-old) 5xFAD and WT mice, we have studied the physiological response, firing rate, and burst of RGCs to various types of visual stimuli using a multielectrode array system. Results: The firing rate and burst response in 5xFAD RGCs showed hyperactivity at the early stage of AD in young mice, whereas hypoactivity was seen at the later stage of AD in adults. The physiological alterations observed in 5xFAD correlate well with an increase in the expression of glutamate in the ganglion cell layer in young and adults. GABA staining increased in the inner nuclear and plexiform layer, which was more pronounced in the adult than the young 5xFAD retina, altering the excitation/inhibition balance, which could explain the observed early hyperactivity and later hypoactivity in RGC physiology. Conclusion: These findings indicate functional changes may be caused by neurochemical alterations of the retina starting at an early stage of the AD disease. |
Databáze: | OpenAIRE |
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