The role of GFAP and vimentin in learning and memory

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.

Neuronal p38α mediates age‐associated neural stem cell exhaustion and cognitive decline

“…Specifically, aged p38α∆‐N mice displayed higher levels of IL7, a cytokine that promotes neuronal survival (Michaelson, Mehler, Xu, Gross, & Kessler, ), and decreased levels of the chemokines CCL11 and CXCL1, whose elevation has been associated with systemic aging, and their high levels are detrimental to neurogenesis and cognitive function, particularly in the case of CCL11 (Villeda et al, ; Wolfe, Minogue, Rooney, & Lynch, ). Moreover, we also detected higher VIMENTINE levels, which are associated with astrocyte activation and mobilization (Liu et al, ; Wilhelmsson et al, ). Thus, the positive impact of p38α deletion, and consequent reduction in p38MAPK activity, in neurons is likely mediated by controlling the neuroinflammatory status of the niche.…”

Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

“…Correspondingly, some studies proposed that knockout/knockdown of molecules produced by astrocytes or suppression of astrocyte-related signaling enhances neurogenesis. Mice devoid of GFAP and vimentin are found to be developmentally normal with increased hippocampal neurogenesis and axonal regeneration post-TBI, despite that GFAP is essential for astrocyte activation and acute cellular stress handling [97][98][99][100]. This disparity may be due to the mechanism that differentiation of uncommitted neural progenitor cells is skewed towards neuronal lineage under the null of GFAP gene condition, and inhibition of Sirt1 expression may strengthen this inclination [101].…”

Repetitive injury and absence of monocytes promote astrocyte self‐renewal and neurological recovery

“…Astrocytes are key for brain function (Chai et al, 2017; Jahn, Scheller, & Kirchhoff, 2015; Oberheim, Goldman, & Nedergaard, 2012), providing metabolic support for neurons and regulating synapse function and plasticity at various levels (Araque et al, 2014; Ben Haim & Rowitch, 2017; Dallerac & Rouach, 2016; Verkhratsky & Nedergaard, 2016). In order to perform these functions, astrocytes must cover the entire parenchyma and tiling mechanisms have been suggested to ensure equal coverage by the fine astrocyte processes (Hol & Pekny, 2015; Verkhratsky & Nedergaard, 2016; Wilhelmsson et al, 2019). Despite the importance of astrocyte coverage, very little is known about this after brain injury.…”