Astrocyte-neuronal network interplay is disrupted in Alzheimer's disease mice

Justin Lines, Andres M Baraibar, Cenxiao Fang, Eduardo D. Martin, Juan Aguilar, Michael K Lee, Alfonso Araque, Paulo Kofuji

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is associated with senile plaques of beta-amyloid (Aβ) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aβ on astroglial and neuronal network function remains unknown. Simultaneously monitoring astrocyte calcium and electric neuronal activities, we quantified the impact of Aβ on sensory-evoked cortical activity in a mouse model of AD. At rest, cortical astrocytes displayed spontaneous hyperactivity that was related to Aβ density. Sensory-evoked astrocyte responsiveness was diminished in AD mice, depending on the density and distance of Aβ, and the responses showed altered calcium dynamics. Hence, astrocytes were spontaneously hyperactive but hypo-responsive to sensory stimulation. Finally, AD mice showed sensory-evoked electrical cortical hyperresponsiveness associated with altered astrocyte-neuronal network interplay. Our findings suggest dysfunction of astrocyte networks in AD mice may dysregulate cortical electrical activity and contribute to cognitive decline.

Original languageEnglish (US)
Pages (from-to)368-378
Number of pages11
JournalGlia
Volume70
Issue number2
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
We thank Hajime Hirase for the generous gift of GCaMP7 mice; Dana Deters, Stephanie Nistler, Ruth Quintana and Anshika Rai for technical support; Michelle Corkrum, Caitlin Durkee, Ana Covelo, Mario Martin-Fernandez, Austin Ferro, Joyce Meints, Carmen Perez, Julianna Goenaga, Jos? Noriega and Francisco Labrada for helpful suggestions; Mark Sanders, Guillermo Marques, and Jason Mitchell at the University of Minnesota ? University Imaging Centers for assistance using the Leica SP5 multiphoton upright microscope. This work was supported by National Institutes of Health-MH (R01MH119355) to P.K. and A.A; National Institutes of Health-NINDS (R01NS097312), National Institutes of Health-NIDA (R01DA048822) to A.A.; National Institutes of Health-NIA (1F31AG057155) and the University of Minnesota Doctoral Dissertation Fellowship to J.L.; National Institutes of Health-NIA (1RF1AG062135) to M.K.L.; Salvador de Madariaga Program (PRX19/00646) and Ministerio de Ciencia, Innovaci?n y Universidades (BFU2017-88393-P), Spain, and AEI/FEDER, EU, to E.D.M.; Ministerio de Econom?a y Competitividad (BFU2016-80665-P), Spain, Ayudas para la Movilidad de Investigadores M-BAE (BA15/00078) del Instituto de Salud Carlos III, Spain, and co-funded by FEDER (?A way to make Europe?) to J.A.; Postdoctoral fellowship from the Basque Government to A.M.B.

Funding Information:
Ayudas para la Movilidad de Investigadores, Grant/Award Number: BA15/00078; Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number: BFU2017‐88393‐P; Ministerio de Economía y Competitividad, Grant/Award Number: BFU2016‐80665‐P; National Institute of Mental Health, Grant/Award Number: R01MH119355; National Institute of Neurological Disorders and Stroke, Grant/Award Number: R01NS097312; National Institute on Aging, Grant/Award Numbers: 1F31AG057155, 1RF1AG062135; National Institute on Drug Abuse, Grant/Award Number: R01DA048822; Salvador de Madariaga Program, Grant/Award Number: PRX19/00646 Funding information

Funding Information:
We thank Hajime Hirase for the generous gift of GCaMP7 mice; Dana Deters, Stephanie Nistler, Ruth Quintana and Anshika Rai for technical support; Michelle Corkrum, Caitlin Durkee, Ana Covelo, Mario Martin‐Fernandez, Austin Ferro, Joyce Meints, Carmen Perez, Julianna Goenaga, José Noriega and Francisco Labrada for helpful suggestions; Mark Sanders, Guillermo Marques, and Jason Mitchell at the University of Minnesota – University Imaging Centers for assistance using the Leica SP5 multiphoton upright microscope. This work was supported by National Institutes of Health‐MH (R01MH119355) to P.K. and A.A; National Institutes of Health‐NINDS (R01NS097312), National Institutes of Health‐NIDA (R01DA048822) to A.A.; National Institutes of Health‐NIA (1F31AG057155) and the University of Minnesota Doctoral Dissertation Fellowship to J.L.; National Institutes of Health‐NIA (1RF1AG062135) to M.K.L.; Salvador de Madariaga Program (PRX19/00646) and Ministerio de Ciencia, Innovación y Universidades (BFU2017‐88393‐P), Spain, and AEI/FEDER, EU, to E.D.M.; Ministerio de Economía y Competitividad (BFU2016‐80665‐P), Spain, Ayudas para la Movilidad de Investigadores M‐BAE (BA15/00078) del Instituto de Salud Carlos III, Spain, and co‐funded by FEDER (“”) to J.A.; Postdoctoral fellowship from the Basque Government to A.M.B. A way to make Europe

Publisher Copyright:
© 2021 Wiley Periodicals LLC.

Keywords

  • APP/PS1
  • Alzheimer's disease
  • astrocyte
  • astrogliosis
  • beta amyloid
  • cortex

PubMed: MeSH publication types

  • Journal Article

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