Octodon degus, toward its consolidation as a natural model of Alzheimer`s disease
Fecha
20182018
Institución
Resumen
Alzheimer`s disease (AD) is the leading cause of age-related dementia worldwide. No therapy is currently available to stops or reverses the progression of
AD. Because of the disappointing results obtained in different clinical trials, the identification of new therapeutic alternatives and more reliable models of AD
are very important. In this regard, Octodon degus, a Chilean rodent has been found to spontaneously develop neuropathological signs of AD, including
amyloid-β peptide (Aβ) aggregates, as well as post-synaptic dysfunction. Aging is an important factor in the cognitive function impairment exhibited by O.
degus, which can be related with a decrease in synaptic function and the appearance of AD pathological hallmarks. Moreover, the capacity of O. degus Aβ
to aggregate constitutes a relevant issue toward its usefulness as a natural AD model. Thus, in the present work, we study the capacity of O. degus Aβ1-40
to aggregate in vitro and to form oligomers and amyloid fibrils, evaluated at the electron microscopy level. Moreover, we evaluated the appearance and
distribution of thioflavin-S, 6E10 and 4G8 positive amyloid plaques during aging in “wild-caught O. degus”, and compared them with the amyloid plaques
present in two different transgenic mice, the double transgenic APP/PS1 and the J20 transgenic AD mouse models, including with an evaluation of its threedimensional
structure. Amyloid plaques first appear in anterior brain structures of O. degus around 32 month-old, and in the whole brain after 56 month-old.
Although the total number of plaques (N° plaques/mm2) was lower than in transgenic animals, the amyloid plaques size was bigger in old O. degus brains in
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comparison with the transgenic mice used for comparison. Consistent with our previous works, our current findings allows us to conclude that under specific
environmental conditions O. degus develops several molecular and physiological alterations resembling the AD pathophysiology, including the age-related
progression of Aβ aggregates across the brain. Therefore, we confirm that the Chilean rodent Octodon degus constitutes a “natural” model of AD, and
constitutes a valuable tool to search for therapeutic strategies against AD.