Retinal Ganglion Cells Functional Changes in a Mouse Model of Alzheimer’s Disease Are Linked with Neurotransmitter Alterations

Issue title: Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America

Guest editors: K.S. Jagannatha Rao, Gabrielle B. Britton, Luisa Lilia Rocha Arrieta, Norberto Garcia-Cairasco, Alberto Lazarowski, Adrián Palacios, Antoni Camins Espuny and Ricardo B. Maccioni

Article type: Research Article

Authors: Araya-Arriagada, Joaquín^{a; g; *} | Bello, Felipe^b | Shivashankar, Gaganashree^c | Neira, David^a | Durán-Aniotz, Claudia^f | Acosta, Mónica L.^c | Escobar, María José^e | Hetz, Claudio^d | Chacón, Max^b | Palacios, Adrián G.^{a; *}

Affiliations: [a] Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile | [b] Department of Engineering Informatics, Universidad de Santiago, Santiago, Chile | [c] School of Optometry and Vision Science; Centre for Brain Research; Brain Research New Zealand; The University of Auckland, Auckland, New Zealand | [d] Biomedical Neuroscience Institute, Universidad de Chile, Santiago, Chile | [e] Departamento de Electrónica, Universidad Técnica Federico Santa María, Valparaíso, Chile | [f] Center for Social and Cognitive Neuroscience, School of Psychology, Universidad Adolfo Ibáñez, Santiago de Chile, Chile | [g] Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Chile

Correspondence: [*] Correspondence to: Dr. Joaquín Araya, Pasaje Harrington 287, Playa Ancha, Valparaíso, Chile. Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.; E-mail: [email protected]. and Dr. Adrián G. Palacios, Pasaje Harrington 287, Playa Ancha, Valparaíso, Chile. Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.; E-mail: [email protected].

Abstract: 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.

Keywords: Alzheimer’s disease, GABA, glutamate, retinal ganglion cells, 5xFAD transgenic mice

DOI: 10.3233/JAD-201195

Journal: Journal of Alzheimer's Disease, vol. 82, no. s1, pp. S5-S18, 2021