Electron Microscopy Analysis of Astrocyte-synapse Interactions Shows Altered Dynamics in an Alzheimer's Disease Mouse Model

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2023 Feb 13

PMID 36779013

Authors

Mandy S J Kater

Aina Badia-Soteras

Jan R T van Weering

August B Smit

Mark H G Verheijen

Affiliations

Soon will be listed here.

Abstract

Introduction: Astrocyte-synapse bi-directional communication is required for neuronal development and synaptic plasticity. Astrocytes structurally interact with synapses using their distal processes also known as leaflets or perisynaptic astrocytic processes (PAPs). We recently showed that these PAPs are retracted from hippocampal synapses, and involved in the consolidation of fear memory. However, whether astrocytic synaptic coverage is affected when memory is impaired is unknown.

Methods: Here, we describe in detail an electron microscopy method that makes use of a large number of 2D images to investigate structural astrocyte-synapse interaction in paraformaldehyde fixed brain tissue of mice.

Results And Discussion: We show that fear memory-induced synaptic activation reduces the interaction between the PAPs and the presynapse, but not the postsynapse, accompanied by retraction of the PAP tip from the synaptic cleft. Interestingly, this retraction is absent in the APP/PS1 mouse model of Alzheimer's disease, supporting the concept that alterations in astrocyte-synapse coverage contribute to memory processing.

Citing Articles

Scaled Complexity of Mammalian Astrocytes: Insights From Mouse and Macaque.

Heffernan K, Martinez I, Jaeger D, Khakh B, Smith Y, Galvan A J Comp Neurol. 2024; 532(8):e25665.

PMID: 39235147 PMC: 11378921. DOI: 10.1002/cne.25665.

Astrocyte morphology.

Baldwin K, Murai K, Khakh B Trends Cell Biol. 2024; 34(7):547-565.

PMID: 38180380 PMC: 11590062. DOI: 10.1016/j.tcb.2023.09.006.

Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism.

Kotah J, Kater M, Brosens N, Lesuis S, Tandari R, Blok T Alzheimers Dement. 2023; 20(3):1637-1655.

PMID: 38055782 PMC: 10984508. DOI: 10.1002/alz.13569.

Comparative assessment of the effects of DREADDs and endogenously expressed GPCRs in hippocampal astrocytes on synaptic activity and memory.

Lee S, Mak A, Verheijen M Front Cell Neurosci. 2023; 17:1159756.

PMID: 37051110 PMC: 10083367. DOI: 10.3389/fncel.2023.1159756.

References

Sapkota D, Kater M, Sakers K, Nygaard K, Liu Y, Koester S . Activity-dependent translation dynamically alters the proteome of the perisynaptic astrocyte process. Cell Rep. 2022; 41(3):111474. PMC: 9624251. DOI: 10.1016/j.celrep.2022.111474. View

Khakh B, Sofroniew M . Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci. 2015; 18(7):942-52. PMC: 5258184. DOI: 10.1038/nn.4043. View

Perez-Alvarez A, Navarrete M, Covelo A, Martin E, Araque A . Structural and functional plasticity of astrocyte processes and dendritic spine interactions. J Neurosci. 2014; 34(38):12738-44. PMC: 6705321. DOI: 10.1523/JNEUROSCI.2401-14.2014. View

Kater M, Huffels C, Oshima T, Renckens N, Middeldorp J, Boddeke E . Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer's disease. Brain Behav Immun. 2022; 107:225-241. DOI: 10.1016/j.bbi.2022.10.009. View

Kubota Y, Sohn J, Kawaguchi Y . Large Volume Electron Microscopy and Neural Microcircuit Analysis. Front Neural Circuits. 2018; 12:98. PMC: 6240581. DOI: 10.3389/fncir.2018.00098. View

Molotkov D, Zobova S, Arcas J, Khiroug L . Calcium-induced outgrowth of astrocytic peripheral processes requires actin binding by Profilin-1. Cell Calcium. 2013; 53(5-6):338-48. DOI: 10.1016/j.ceca.2013.03.001. View

Hulshof L, van Nuijs D, Hol E, Middeldorp J . The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review. Front Cell Neurosci. 2022; 16:899251. PMC: 9244621. DOI: 10.3389/fncel.2022.899251. View

Santello M, Toni N, Volterra A . Astrocyte function from information processing to cognition and cognitive impairment. Nat Neurosci. 2019; 22(2):154-166. DOI: 10.1038/s41593-018-0325-8. View

Benediktsson A, Schachtele S, Green S, Dailey M . Ballistic labeling and dynamic imaging of astrocytes in organotypic hippocampal slice cultures. J Neurosci Methods. 2004; 141(1):41-53. DOI: 10.1016/j.jneumeth.2004.05.013. View

10.

Bezzi P, Volterra A . A neuron-glia signalling network in the active brain. Curr Opin Neurobiol. 2001; 11(3):387-94. DOI: 10.1016/s0959-4388(00)00223-3. View

11.

Mahmoud S, Gharagozloo M, Simard C, Gris D . Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release. Cells. 2019; 8(2). PMC: 6406900. DOI: 10.3390/cells8020184. View

12.

Ceyzeriat K, Ben Haim L, Denizot A, Pommier D, Matos M, Guillemaud O . Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer's disease. Acta Neuropathol Commun. 2018; 6(1):104. PMC: 6190663. DOI: 10.1186/s40478-018-0606-1. View

13.

Badia-Soteras A, Heistek T, Kater M, Mak A, Negrean A, van den Oever M . Retraction of Astrocyte Leaflets From the Synapse Enhances Fear Memory. Biol Psychiatry. 2023; 94(3):226-238. DOI: 10.1016/j.biopsych.2022.10.013. View

14.

Arizono M, Inavalli V, Panatier A, Pfeiffer T, Angibaud J, Levet F . Structural basis of astrocytic Ca signals at tripartite synapses. Nat Commun. 2020; 11(1):1906. PMC: 7170846. DOI: 10.1038/s41467-020-15648-4. View

15.

Tremblay M, Riad M, Majewska A . Preparation of mouse brain tissue for immunoelectron microscopy. J Vis Exp. 2010; (41). PMC: 3156065. DOI: 10.3791/2021. View

16.

Aarts E, Verhage M, Veenvliet J, Dolan C, van der Sluis S . A solution to dependency: using multilevel analysis to accommodate nested data. Nat Neurosci. 2014; 17(4):491-6. DOI: 10.1038/nn.3648. View

17.

Dallerac G, Chever O, Rouach N . How do astrocytes shape synaptic transmission? Insights from electrophysiology. Front Cell Neurosci. 2013; 7:159. PMC: 3787198. DOI: 10.3389/fncel.2013.00159. View

18.

Rose G, Lynch G, Cotman C . Hypertrophy and redistribution of astrocytes in the deafferented dentate gyrus. Brain Res Bull. 1976; 1(1):87-92. DOI: 10.1016/0361-9230(76)90052-6. View

19.

Ghezali G, Dallerac G, Rouach N . Perisynaptic astroglial processes: dynamic processors of neuronal information. Brain Struct Funct. 2015; 221(5):2427-42. DOI: 10.1007/s00429-015-1070-3. View

20.

Saint-Martin M, Goda Y . Astrocyte-synapse interactions and cell adhesion molecules. FEBS J. 2022; 290(14):3512-3526. DOI: 10.1111/febs.16540. View