Abstract
Intermediate filaments (also termed nanofilaments) are involved in many cellular functions and play important roles in cellular responses to stress. The upregulation of glial fibrillary acidic protein (GFAP) and vimentin (Vim), intermediate filament proteins of astrocytes, is the hallmark of astrocyte activation and reactive gliosis in response to injury, ischemia or neurodegeneration. Reactive gliosis is essential for the protective role of astrocytes at acute stages of neurotrauma or ischemic stroke. However, GFAP and Vim were also linked to neural plasticity and regenerative responses in healthy and injured brain. Mice deficient for GFAP and vimentin (GFAP−/−Vim−/−) exhibit increased post-traumatic synaptic plasticity and increased basal and post-traumatic hippocampal neurogenesis. Here we assessed the locomotor and exploratory behavior of GFAP−/−Vim−/− mice, their learning, memory and memory extinction, by using the open field, object recognition and Morris water maze tests, trace fear conditioning, and by recording reversal learning in IntelliCages. While the locomotion, exploratory behavior and learning of GFAP−/−Vim−/− mice, as assessed by object recognition, the Morris water maze, and trace fear conditioning tests, were comparable to wildtype mice, GFAP−/−Vim−/− mice showed more pronounced memory extinction when tested in IntelliCages, a finding compatible with the scenario of an increased rate of reorganization of the hippocampal circuitry.
Age-related memory deficits are associated with changes in protein degradation in brain regions critical for trace fear conditioning
