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Aging reduces calreticulin expression and alters spontaneous calcium signals in astrocytic endfeet of the mouse dorsolateral striatum

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Zarate, Sara M., Huntington, Taylor E., Bagher, Pooneh, Srinivasan, Rahul·2023·npj Aging
DOI 10.1038/s41514-023-00102-8PMC PMC10066375
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Abstract

Aging-related impairment of the blood brain barrier (BBB) and neurovascular unit (NVU) increases the risk for neurodegeneration. Among various cells that participate in BBB and NVU function, calcium signals in astrocytic endfeet are crucial for maintaining BBB and NVU integrity. To assess if aging is associated with altered calcium signals within astrocytic endfeet of the dorsolateral striatum (DLS), we expressed GCaMP6f in DLS astrocytes of young (3–4 months), middle-aged (12–15 months) and aging (20–30 months) mice. Compared to endfeet in young mice, DLS endfeet in aging mice demonstrated decreased calreticulin expression, and alterations to both spontaneous membrane-associated and mitochondrial calcium signals. While young mice required both extracellular and endoplasmic reticulum calcium sources for endfoot signals, middle-aged and aging mice showed heavy dependence on endoplasmic reticulum calcium. Thus, astrocytic endfeet show significant changes in calcium buffering and sources throughout the lifespan, which is important for understanding mechanisms by which aging impairs the BBB and NVU.

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  • Mitochondria in central nervous system astrocytes are strategically distributed within subcellular regions in the astrocytic territory, endfeet and soma, and since astrocytes generally outnumber neurons in the CNS, astrocytic mitochondria are optimally positioned to cater to the high energy demands of CNS neurons, particularly substantia nigra pars compacta dopaminergic neurons.

    “Mitochondria in CNS astrocytes are strategically distributed within subcellular regions in the astrocytic territory, endfeet and soma”

    From Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism (2026) · cites this paper as Zarate et al. 2023

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Cited by

Sorted by citations

Authors
Zarate, S. M., Huntington, T. E., Bagher, P., & Srinivasan, R.
Affiliations
  • Texas A&M University (US)
  • University of Nebraska Medical Center (US)
Corresponding author
Srinivasan, Rahul
ORCID
Venue
npj Aging
Publisher
Springer Science and Business Media LLC
Published
2023-03-31
Volume
9
Issue
1
Pages
5-5
ISSN
2731-6068 (ISSN-L)
DOI
10.1038/s41514-023-00102-8
PMC
PMC10066375
OpenAlex
W4361988948
Cited by
19
References
3
Citations by year
2026: 13 · 2025: 3 · 2024: 2 · 2022: 1
FWCI
1.78
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Aging (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS115809 (SRINIVASAN))
  • U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (R01HL155618 (BAGHER))
  • American Diabetes Association (1-19-JDF-111 (BAGHER))
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords
aging, calreticulin, astrocytic endfeet, dorsolateral striatum, calcium signaling, blood-brain barrier, neurovascular unit, endoplasmic reticulum calcium, mitochondrial calcium, calcium buffering, GCaMP6f, neurodegeneration

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