Can the retina show similar molecular and cellular changes as the brain in an animal model of Alzheimer’s disease?
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1
Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Portugal
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2
CNC.IBILI Consortium, University of Coimbra, Portugal
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3
Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal
In Alzheimer’s disease (AD), a neurodegenerative disease characterized by the presence of senile plaques and neurofibrillary tangles, the patients present visual complaints, even before the appearance of the first cognitive symptoms. Accordingly, the concept of the retina as a window/mirror to look into the brain has been explored to unravel whether the retina can be used as a diagnostic tool in AD. However, it is vital to assess whether the retina and brain share similar changes in AD. Here, we aimed to unravel whether these regions share molecular and cellular alterations in an AD animal model, at early stages.
Retina, hippocampus and cortex homogenates from male triple transgenic (3xTg-AD, AD model) and age-matched controls (WT, C57BL6/129S) mice, 4 and 8 months-old (M), were used to assess proteins related with AD, synaptic dysfunction and neuroinflammation. The number of retinal ganglion cells (RGCs) and glial cells were assessed by immunohistochemistry and cell death by TUNEL assay.
The 3xTg-AD mice presented increased Aβ levels in the hippocampus and cortex at 4 and 8M. Nevertheless, Aβ was not detected in the retina of 3xTg-AD mice. Increased p-tau levels were observed in the hippocampus of 3xTg-AD at 4 and 8M, although in the retina and cortex increased levels were only detected at 4M. Despite a transient increase of some synaptic proteins in the hippocampus and cortex at 4M, this effect was not observed in the retina. Additionally, the retina and brain of 3xTg-AD mice did not present cell loss. The levels of GFAP (marker of astrocytes) in the hippocampus increased at 4M, while in the retina decreased at 8M. No changes were detected in vimentin protein levels (Müller cells marker). The number of microglial cells did not change in CA1 hippocampal subregion neither in the retina of 3xTg-AD mice.
These data demonstrate that 3xTg-AD mice do not present substantial molecular and cellular changes in the retina and brain at 4 and 8M. However, differential changes were detected in astrocyte reactivity in the retina and brain along time, suggesting that these regions undergo distinct glial changes, at least in early AD.
Acknowledgements
Santa Casa Mantero Belard Award 2015 (MB-1049-2015), Foundation for Science and Technology (PEst UID/NEU/04539/2013), COMPETE-FEDER (POCI-01-0145-FEDER-007440), and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020).
Keywords:
Alzheimer’s disease,
biomarkers,
Brain,
diagnosis,
Retina
Conference:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.
Presentation Type:
Poster presentation
Topic:
Neurodegeneration / Physiological Aging Brain
Citation:
Rodrigues-Neves
A,
Carecho
R,
Baptista
FI,
Moreira
PI and
Ambrósio
AF
(2019). Can the retina show similar molecular and cellular changes as the brain in an animal model of Alzheimer’s disease?.
Front. Cell. Neurosci.
Conference Abstract:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019).
doi: 10.3389/conf.fncel.2019.01.00020
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Received:
16 Apr 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Miss. Ana Catarina Rodrigues-Neves, Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Coimbra, Portugal, catarinaneves.fctuc@gmail.com