Exacerbated age-related hippocampal alterations of microglia morphology, β-amyloid and lipofuscin deposition and presenilin overexpression in Per1-/--mice

  • In humans, alterations of circadian rhythms and autophagy are linked to metabolic, cardiovascular and neurological dysfunction. Autophagy constitutes a specific form of cell recycling in many eukaryotic cells. Aging is the principal risk factor for the development of neurodegenerative diseases. Thus, we assume that both the circadian clock and autophagy are indispensable to counteract aging. We have previously shown that the hippocampus of Per1−/−-mice exhibits a reduced autophagy and higher neuronal susceptibility to ischemic insults compared to wild type (WT). Therefore, we chose to study the link between aging and loss of clock gene Per1−/−-mice. Young and aged C3H- and Per1−/−-mice were used as models to analyze the hippocampal distribution of Aβ42, lipofuscin, presenilin, microglia, synaptophysin and doublecortin. We detected several changes in the hippocampus of aged Per1−/−-mice compared to their wild type littermates. Our results show significant alterations of microglia morphology, an increase in Aβ42 deposition, overexpression of presenilin, decrease in synaptophysin levels and massive accumulation of lipofuscin in the hippocampus of 24-month-old Per1−/−-mice, without alteration of adult neurogenesis. We suggest that the marked lipofuscin accumulation, Aβ42 deposition, and overexpression of presenilin-2 observed in our experiments may be some of the consequences of the slowed autophagy in the hippocampus of aged Per1−/−-mice. This may lead during aging to excessive accumulation of misfolded proteins which may, consequently, result in higher neuronal vulnerability.

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Author:Jan Hendrik Börner, Oliver RawashdehORCiD, Abdelhaq RamiORCiDGND
Parent Title (English):Antioxidants
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/08/24
Date of first Publication:2021/08/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/09/22
Tag:Per1−/−-mice; aging; autophagy; hippocampus; lipofuscin; microglia; oxidative stress; ß-amyloid
Issue:9, art. 1330
Page Number:19
First Page:1
Last Page:19
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0