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cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology
Sakiko Ujita1, Takuya Sasaki1, Akiko Asada1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Cerebral Cortex (New York, N.Y. : 1991)
|January 24, 2016
Summary
Regular calcium oscillations in astrocytes, observed using advanced imaging, indicate a potential pathological state. This activity, linked to reactive gliosis, may offer insights into neurological conditions like epilepsy and ischemia.
Area of Science:
- Neuroscience
- Cell Biology
- Astrocyte Biology
Background:
- Astrocytes exhibit spontaneous intracellular calcium (Ca2+) elevations in the brain.
- The temporal patterns and functional significance of astrocytic Ca2+ activity remain incompletely understood.
Purpose of the Study:
- To investigate the temporal dynamics and characteristics of spontaneous astrocytic Ca2+ activity.
- To determine the functional implications and cellular mechanisms of observed astrocytic Ca2+ oscillations.
Main Methods:
- Long-term optical imaging of over 4000 astrocytes in acute brain slices and head-restrained mice (neocortex and hippocampus).
- Analysis of Ca2+ oscillation patterns, dependence on specific receptors (IP3R2), intracellular signaling pathways (cAMP-PKA), and neuronal activity.
- Assessment of astrocytic process hypertrophy and association with pathological conditions.
Main Results:
- Astrocytic Ca2+ activity is generally sparse and irregular, but a subset of astrocytes displays regular oscillations (∼30 s intervals).
- These oscillations depend on inositol 1,4,5-trisphosphate receptors (IP3R2), involve complex intracellular signaling, and are independent of neuronal firing.
- Oscillations are modulated by cAMP-protein kinase A (PKA) signaling and are enhanced under pathological conditions (energy deprivation, hyperexcitation), correlating with astrocytic process hypertrophy.
Conclusions:
- Regular astrocytic Ca2+ oscillations are linked to specific intracellular mechanisms and signaling pathways.
- These oscillations are facilitated under pathological conditions and associated with reactive gliosis, suggesting a role in neurological disease states.
- The findings highlight astrocytic Ca2+ oscillations as a potential biomarker or contributor to neuropathology.
