Nestin Null Mice Show Improved Reversal Place Learning

Wilhelmsson, Ulrika; Kalm, Marie; Pekna, Marcela; Pekny, Milos

doi:10.1007/s11064-019-02854-w

Cited by 6 publications

(7 citation statements)

References 38 publications

(48 reference statements)

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“…Nestin is upregulated in reactive astrocytes and expressed during CNS development in neural stem cells, immature astrocytes, and in some astrocytes in the unchallenged adult CNS . We recently demonstrated that nestin in astrocytes plays an important role in adult hippocampal neurogenesis, that Jagged‐1 internalization and vesicle compartmentalization is altered in nestin‐deficient ( Nes −/− ) astrocytes, and that nestin absence leads to improved reversal place learning and memory extinction . In this study, we investigated vesicle dynamics in Nes −/− astrocytes and demonstrated a role of nestin in regulating exo‐/endocytosis, the fusion pore, vesicle mobility and astrocyte Ca 2+ signalling.…”

Section: Introductionmentioning

confidence: 92%

“…59 We recently demonstrated that nestin in astrocytes plays an important role in adult hippocampal neurogenesis, 59 that Jagged-1 internalization and vesicle compartmentalization is altered in nestin-deficient (Nes −/− ) astrocytes, and that nestin absence leads to improved reversal place learning and memory extinction. 60 In this study, we investigated vesicle dynamics in Nes −/− astrocytes and demonstrated a role of nestin in regulating exo-/endocytosis, the fusion pore, vesicle mobility and astrocyte Ca 2+ signalling. Such a role of nestin in astroglial vesicle-based mechanisms could affect signalling between astrocytes and other neural cells in the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Nestin affects fusion pore dynamics in mouse astrocytes

et al. 2019

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Aim Astrocytes play a homeostatic role in the central nervous system and influence numerous aspects of neurophysiology via intracellular trafficking of vesicles. Intermediate filaments (IFs), also known as nanofilaments, regulate a number of cellular processes including organelle trafficking and adult hippocampal neurogenesis. We have recently demonstrated that the IF protein nestin, a marker of neural stem cells and immature and reactive astrocytes, is also expressed in some astrocytes in the unchallenged hippocampus and regulates neurogenesis through Notch signalling from astrocytes to neural stem cells, possibly via altered trafficking of vesicles containing the Notch ligand Jagged‐1. Methods We thus investigated whether nestin affects vesicle dynamics in astrocytes by examining single vesicle interactions with the plasmalemma and vesicle trafficking with high‐resolution cell‐attached membrane capacitance measurements and confocal microscopy. We used cell cultures of astrocytes from nestin‐deficient (Nes−/−) and wild‐type (wt) mice, and fluorescent dextran and Fluo‐2 to examine vesicle mobility and intracellular Ca2+ concentration respectively. Results Nes−/− astrocytes exhibited altered sizes of vesicles undergoing full fission and transient fusion, altered vesicle fusion pore geometry and kinetics, decreased spontaneous vesicle mobility and altered ATP‐evoked mobility. Purinergic stimulation evoked Ca2+ signalling that was slightly attenuated in Nes−/− astrocytes, which exhibited more oscillatory Ca2+ responses than wt astrocytes. Conclusion These results demonstrate at the single vesicle level that nestin regulates vesicle interactions with the plasmalemma and vesicle trafficking, indicating its potential role in astrocyte vesicle‐based communication.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Nestin affects fusion pore dynamics in mouse astrocytes

et al. 2019

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“…The absence of nestin in astrocytes likely impairs notch signaling by affecting trafficking as well as the exo- and endocytosis of vesicles containing the Notch ligand, Jagged-1 [ 137 , 138 ]. As a functional consequence of impaired notch signalling, nestin-deficient (Nes −/− ) mice showed improved (reversal place) learning as well as memory extinction on account of facilitated forgetting [ 51 , 139 ].…”

Section: Nestinmentioning

confidence: 99%

The Diversity of Intermediate Filaments in Astrocytes

Potokar

Morita

Wiche

et al. 2020

Cells

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Despite the remarkable complexity of the individual neuron and of neuronal circuits, it has been clear for quite a while that, in order to understand the functioning of the brain, the contribution of other cell types in the brain have to be accounted for. Among glial cells, astrocytes have multiple roles in orchestrating neuronal functions. Their communication with neurons by exchanging signaling molecules and removing molecules from extracellular space takes place at several levels and is governed by different cellular processes, supported by multiple cellular structures, including the cytoskeleton. Intermediate filaments in astrocytes are emerging as important integrators of cellular processes. Astrocytes express five types of intermediate filaments: glial fibrillary acidic protein (GFAP); vimentin; nestin; synemin; lamins. Variability, interactions with different cellular structures and the particular roles of individual intermediate filaments in astrocytes have been studied extensively in the case of GFAP and vimentin, but far less attention has been given to nestin, synemin and lamins. Similarly, the interplay between different types of cytoskeleton and the interaction between the cytoskeleton and membranous structures, which is mediated by cytolinker proteins, are understudied in astrocytes. The present review summarizes the basic properties of astrocytic intermediate filaments and of other cytoskeletal macromolecules, such as cytolinker proteins, and describes the current knowledge of their roles in normal physiological and pathological conditions.

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“…Plectin is a quintessential component of the cytoskeleton meshwork. On the one hand, it connects to microtubules and actin filaments that affect vesicle trafficking and organelle positioning [ 5 , 28 , 29 ], and on the other hand, it links extensively to IFs, which have multiple structural functions and modulate signal transduction in the CNS [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Thus, plectin is crucially positioned to fine-tune a myriad of cellular functions in cells of the CNS.…”

Section: Plectin In Specific Cell Types In the Central Nervous Systemmentioning

confidence: 99%

Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes

Potokar

Jorgačevski

2021

Cells

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Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule. Thus, it is likely involved in signalling processes, thereby affecting numerous fundamental functions in the brain and spinal cord. Versatile direct and indirect interactions of plectin with cytoskeletal filaments and enzymes in the cells of the CNS in normal physiological and in pathologic conditions remain to be fully addressed. Several pathologies of the CNS related to plectin have been discovered in patients with plectinopathies. However, in view of plectin as an integrator of a cohesive mesh of cellular proteins, it is important that the role of plectin is also considered in other CNS pathologies. This review summarizes the current knowledge of plectin in the CNS, focusing on plectin isoforms that have been detected in the CNS, along with its expression profile and distribution alongside diverse cytoskeleton filaments in CNS cell types. Considering that the bidirectional communication between neurons and glial cells, especially astrocytes, is crucial for proper functioning of the CNS, we place particular emphasis on the known roles of plectin in neurons, and we propose possible roles of plectin in astrocytes.

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Nestin Null Mice Show Improved Reversal Place Learning

Cited by 6 publications

References 38 publications

Nestin affects fusion pore dynamics in mouse astrocytes

Nestin affects fusion pore dynamics in mouse astrocytes

The Diversity of Intermediate Filaments in Astrocytes

Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes

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