Age-dependent effects of dimethyl fumarate on cognitive and neuropathological features in the streptozotocin-induced rat model of Alzheimer’s disease
PBN-AR
Instytucja
Wydział Biologii (Uniwersytet Gdański)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Brain Research (25pkt w roku publikacji)
ISSN
0006-8993
EISSN
1872-6240
Wydawca
DOI
URL
Rok publikacji
2018
Numer zeszytu
Strony od-do
19-33
Numer tomu
1686
Identyfikator DOI
Liczba arkuszy
0.7
Słowa kluczowe
en
dimethyl fumarate
memory disorder
streptozotocin
neurodegeneration
microglia
Alzheimer’s disease
age
Streszczenia
Język
en
Treść
We previously demonstrated that dimethyl fumarate (DMF), an anti-oxidative and immunosuppresive compound, prevents intracerebroventricular (ICV) streptozotocin-induced disruption of spatial memory and neurodegeneration in 4-month-old rats. The present study evaluated the influence of age on DMF’s therapeutic effect. Aged rats (22-months-old, n = 40) were provided rodent chow containing DMF (0.4%) and given ICV injections of streptozotocin (STZ) or vehicle (Sham) on days 2 and 4. Spatial memory was evaluated using the Morris water maze (MWM) on days 14–21. Hippocampal samples from young (4- month-old, n = 36, collected previously) and aged rats were assessed for presence of activated (CD68- positive) microglia, IL-10 and oxidative/nitrative stress marker nitrotyrosine. Aged rat samples were also stained with Fluoro-Jade B marker for neurodegeneration. Previously obtained MWM and Fluoro-Jade B data from young rats served as a reference for assessing impact of age. Aged Sham DMF-fed rats exhibited better spatial memory and less neurodegeneration in the CA3 region of the hippocampus compared to corresponding young rats. Aged STZ rats displayed greater memory impairment and increased CA2 neurodegeneration, CA1 nitrotyrosine immunoreactivity, and microglial activation in the dentate gyrus (DG), compared to young STZ rats. Notably, within aged STZ-injected rats, DMF treatment was associated with improved performance in MWM, reduced neurodegeneration in all hippocampal areas, reduced DG microglia activation, and reduced CA1 nitrotyrosine labeling compared to age-matched rats without DMF treatment. This beneficial age-related effect of DMF treatment after STZ ICV injections may result from reduced microglial activation in the hippocampus that leads to an alleviation of oxidative stress, neurodegeneration, and memory impairments.
Inne
System-identifier
UOG05311bf4f3ff41ffb58ea8018d5e386b
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