Compartment-specific analysis reveals disrupted astrocytic calcium transients in anesthetized Alzheimer's disease mice
Md Joynal Abedin, Yee Fun Lee, Melinda Zhang, Alyssa N Russ, Dmitry Gerashchenko, Brian J. Bacskai, Ksenia V. KastanenkaBackground
Alzheimer's disease (AD) is characterized by presence of extracellular amyloid plaques, intracellular tau tangles, and extensive neuronal cell death. In addition to neurons, astrocytes modulate neuronal network activity through tripartite synapses. Also, astrocytes are increasingly recognized for their involvement in AD pathology. Aberrant astrocytic calcium signaling has been implicated in AD pathological processes, including disrupted synaptic transmission, dysregulated glutamate homeostasis, and impaired vascular function via astrocytic endfeet. Previous investigations have assessed compartment-specific astrocytic calcium transients, yet most employed a restricted range of metrics. Thus, comprehensive analyses of calcium dynamics within individual astrocytic compartments in mouse models of amyloidosis are lacking.
Objective
To analyze spontaneous calcium transients within distinct astrocytic compartments in APP/PS1 mice.
Methods
Using in vivo multiphoton imaging of Yellow Cameleon 3.6, a genetically encoded calcium indicator targeted to astrocytes in APP/PS1 mice, we analyzed spontaneous calcium transients in cortical astrocytes at 4–6 months of age. We quantified event rate, activity duration, area under the curve (AUC), and peak amplitude across four compartments: soma, processes, microdomains, and endfeet. Correlation analyses were used to assess astrocyte synchrony and distance-dependent activity relationships.
Results
In APP/PS1 mice, somas exhibited increased activity duration and peak amplitude, while processes and microdomains showed reduced duration, AUC, and amplitude despite higher event rates. Endfeet showed reductions in all parameters. Correlation analyses revealed enhanced astrocyte synchrony in APP/PS1 mice, with distance-dependent correlation decay observed only in nontransgenic controls.
Conclusions
These findings highlight compartment-specific disruptions of astrocytic calcium activity caused by amyloidosis.