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Published on: November 19, 2014
The Effect of the Optogenetic Stimulation of Astrocytes on Neural Network Activity in an In Vitro Model of
Elena V Mitroshina1, Elizaveta P Kalinina1, Alena I Kalyakulina2,3
1Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Avenue, 603022 Nizhny Novgorod, Russia.
Abstract:
Optogenetics is a combination of optical and genetic technologies used to activate or, conversely, inhibit specific cells in living tissues. The possibilities of using optogenetics approaches for the treatment of epilepsy, Parkinson's and Alzheimer's disease (AD) are being actively researched. In recent years, it has become clear that one of the most important players in the development of AD is astrocytes. Astrocytes affect amyloid clearance, participate in the development of neuroinflammation, and regulate the functioning of neural networks. We used an adeno-associated virus carrying the glial fibrillary acidic protein (GFAP) promoter driving the optogenetic channelrhodopsin-2 (ChR2) gene to transduce astrocytes in primary mouse hippocampal cultures. We recorded the bioelectrical activity of neural networks from day 14 to day 21 of cultivation using multielectrode arrays. A single optogenetic stimulation of astrocytes at 14 day of cultivation (DIV14) did not cause significant changes in neural network bioelectrical activity. Chronic optogenetic stimulation from DIV14 to DIV21 exerts a stimulatory effect on the bioelectrical activity of primary hippocampal cultures (the proportion of spikes included in network bursts significantly increased since DIV19). Moreover, chronic optogenetic stimulation over seven days partially preserved the activity and functional architecture of neuronal network in amyloidosis modeling. These results suggest that the selective optogenetic activation of astrocytes may represent a promising novel therapeutic strategy for combating AD.
Insights
Optogenetics can modulate astrocyte activity to potentially treat Alzheimer's disease (AD). Chronic stimulation of astrocytes improved neural network function and preserved architecture in models of AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Astrocytes play a critical role in Alzheimer's disease (AD) pathogenesis, influencing amyloid clearance, neuroinflammation, and neural network function.
- Optogenetics offers a method to precisely control cellular activity using light and genetic engineering.
Purpose of the Study:
- To investigate the therapeutic potential of optogenetically activating astrocytes for Alzheimer's disease treatment.
- To examine the effects of chronic optogenetic stimulation of astrocytes on neural network activity and network architecture in an AD model.
Main Methods:
- Utilized an adeno-associated virus (AAV) vector with a GFAP promoter to drive Channelrhodopsin-2 (ChR2) expression in astrocytes.
- Cultured primary mouse hippocampal neurons and applied chronic optogenetic stimulation to astrocytes from 14 to 21 days in vitro (DIV14-DIV21).
- Recorded and analyzed neural network bioelectrical activity using multielectrode arrays, including network burst analysis and functional architecture assessment.
Main Results:
- Single optogenetic stimulation of astrocytes at DIV14 did not significantly alter neural network activity.
- Chronic optogenetic stimulation from DIV14 to DIV21 significantly increased the proportion of spikes within network bursts, indicating enhanced network activity.
- Seven days of chronic optogenetic stimulation partially preserved neural network activity and functional architecture in an amyloidosis model.
Conclusions:
- Selective optogenetic activation of astrocytes demonstrates a stimulatory effect on neural network bioelectrical activity.
- Chronic optogenetic stimulation of astrocytes shows promise in preserving neuronal network function in Alzheimer's disease models.
- Targeting astrocytes via optogenetics represents a potential novel therapeutic strategy for Alzheimer's disease.
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