Dentate gyrus astrocytes exhibit layer-specific molecular, morphological and physiological features

Karpf, Julian; Unichenko, Petr; Chalmers, Nicholas; Beyer, Felix; Wittmann, Marie-Theres; Schneider, Júlia; Fidan, Elif; Reis, André; Beckervordersandforth, Jan; Brandner, Sebastian; Liebner, Stefan; Falk, Sven; Sagner, Andreas; Henneberger, Christian; Beckervordersandforth, Ruth

doi:10.1038/s41593-022-01192-5

Cited by 31 publications

(36 citation statements)

References 60 publications

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“…For example, cortical protoplasmic astrocytes were found to display four prominent morphological subtypes, which distribute in differing proportions through the various cortical layers [29], which may reflect differences in local neuronal activity [30]. Likewise, astrocytes in the dentate gyrus (DG) have also been shown to display morphological heterogeneity linked to DG layering [31]. Astrocyte peripheral processes have received considerable attention as their terminal ends are thought to interact with neurons -creating a structure widely referred to as the 'tripartite synapse' .…”

Section: Morphologymentioning

confidence: 99%

“…variability both within and between brain regions (see above) [28,29,31] -although methodological differences cannot be completely discounted at this stage. Nevertheless, the general consensus appears to be that astrocyte processes are much more structurally heterogeneous than previous thought, and this is likely to support specialized interactions with local neuronal circuits.…”

Section: Morphologymentioning

confidence: 99%

“…These astrocytic laminae were defined by specific patterns of gene expression, including genes involved in synapse formation and maturation, such as Chrdl1, among others [53]. A similar layering of molecularly distinct astrocytes in DG [31], and the differential expression of μ-crystallin along the dorsal-ventral axis in striatal astrocytes, suggests regional substructure may be a more widespread phenomenon and not restricted to cortex [28].…”

Section: Transcriptome/proteomementioning

confidence: 99%

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Astrocyte heterogeneity and interactions with local neural circuits

Holt

2023

Essays in Biochemistry

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Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into the neuropil, where they interact with a variety of other cell types, including neurons at synapses. Astrocytes are now known to be active players in all aspects of the synaptic life cycle, including synapse formation and elimination, synapse maturation, maintenance of synaptic homeostasis and modulation of synaptic transmission. Traditionally, astrocytes have been studied as a homogeneous group of cells. However, recent studies have uncovered a surprising degree of heterogeneity in their development and function, suggesting that astrocytes may be matched to neurons to support local circuits. Hence, a better understanding of astrocyte heterogeneity and its implications are needed to understand brain function.

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Section: Morphologymentioning

confidence: 99%

Section: Morphologymentioning

confidence: 99%

Section: Transcriptome/proteomementioning

confidence: 99%

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Astrocyte heterogeneity and interactions with local neural circuits

Holt

2023

Essays in Biochemistry

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“…The backbone structure is rich in intermediate filaments such as glial fibrillary acidic protein (GFAP) and microtubule proteins. The size of these structures is in the micrometer range and may be visualized using conventional microscopy (Chai et al, 2017; Eilam et al, 2016; Endo et al, 2022; Grosche et al, 2013; Jones et al, 2018; Karpf et al, 2022; Refaeli et al, 2021; Xu et al, 2014). This structure ramifies to a second level consisting of a mesh‐like network of leaflets that includes perisynaptic processes (PAPs) and end‐feet.…”

Section: Introductionmentioning

confidence: 99%

“…The recent finding that leaflets appear to differentially stem from every astrocytic region (soma, primary processes/branches, and branchlets) (Aten et al, 2022) raised the importance of the properties of astrocytic scaffold that extends to an extensive territory, up to tens of micrometers in the rodent and 2–3 fold more complex in the human brain (Bushong et al, 2002; Livet et al, 2007; Oberheim et al, 2009; Refaeli et al, 2021; Wilhelmsson et al, 2006). Moreover, recent transcriptomic studies described different astrocytic profiles and suggested structural heterogeneity of astrocytes across brain regions (Endo et al, 2022) and within brain regions such as the hippocampus and the cortex (Batiuk et al, 2020; Bayraktar et al, 2020; Karpf et al, 2022). Indeed, a recent study reported that astrocytes in the somatosensory cortex display distinct territorial volume and arborization across the cortical layers (Lanjakornsiripan et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Astrocyte structural heterogeneity in the mouse hippocampus

Viana

Machado

Abreu

et al. 2023

Glia

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Astrocytes are integral components of brain circuits, where they sense, process, and respond to surrounding activity, maintaining homeostasis and regulating synaptic transmission, the sum of which results in behavior modulation. These interactions are possible due to their complex morphology, composed of a tree-like structure of processes to cover defined territories ramifying in a mesh-like system of fine leaflets unresolved by conventional optic microscopy. While recent reports devoted more attention to leaflets and their dynamic interactions with synapses, our knowledge about the tree-like "backbone" structure in physiological conditions is incomplete.Recent transcriptomic studies described astrocyte molecular diversity, suggesting structural heterogeneity in regions such as the hippocampus, which is crucial for cognitive and emotional behaviors. In this study, we carried out the structural analysis of astrocytes across the hippocampal subfields of Cornu Ammonis area 1 (CA1) and dentate gyrus in the dorsoventral axis. We found that astrocytes display heterogeneity across the hippocampal subfields, which is conserved along the dorsoventral axis. We further found that astrocytes appear to contribute in an exocytosis-dependent manner to a signaling loop that maintains the backbone structure. These findings reveal João Filipe Viana and João Luís Machado contributed equally to this study.

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Natural Polyphenolic Nanodots for Alzheimer's Disease Treatment

Yang,

Huang,

Zhang

et al. 2023

Advanced Materials

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The abnormal amyloid‐β accumulation is essential and obbligato in Alzheimer's disease pathogenesis and natural polyphenols exhibit great potential as amyloid aggregation inhibitors. However, the poor metabolic stability, low bioavailability, and weak blood–brain barrier crossing ability of natural polyphenol molecules fail to meet clinical needs. Here, a universal protocol to prepare natural polyphenolic nanodots is developed by heating in aqueous solution without unacceptable additives. The nanodots are able to not only inhibit amyloid‐β fibrillization and trigger the fibril disaggregation, but mitigate the amyloid‐β‐plaque‐induced cascade impairments including normalizing oxidative microenvironment, altering microglial polarization, and rescuing neuronal death and synaptic loss, which results in significant improvements in recognition and cognition deficits in transgenic mice. More importantly, natural polyphenolic nanodots possess stronger antiamyloidogenic performance compared with small molecule, as well as penetrate the blood–brain barrier. The excellent biocompatibility further guarantees the potential of natural polyphenolic nanodots for clinical applications. It is expected that natural polyphenolic nanodots provide an attractive paradigm to support the development of the therapeutics for Alzheimer's disease.

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Dentate gyrus astrocytes exhibit layer-specific molecular, morphological and physiological features

Cited by 31 publications

References 60 publications

Astrocyte heterogeneity and interactions with local neural circuits

Astrocyte heterogeneity and interactions with local neural circuits

Astrocyte structural heterogeneity in the mouse hippocampus

Natural Polyphenolic Nanodots for Alzheimer's Disease Treatment

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