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Subventricular zone neural progenitors reverse TNF-alpha effects in cortical neurons
Raffaella Morini1,2, Elsa Ghirardini3,4, Erica Butti5
1Department of Medical Biotechnology and Traslational Medicine, University of Milano, via Vanvitelli 32, 20129, Milan, Italy. raffaella.morini@humanitasresearch.it.
Stem Cell Research & Therapy
|September 9, 2015
Summary
Adult neural stem cells (aNPCs) counteract tumor necrosis factor alpha (TNFα)-induced neuronal hyperexcitation by activating cannabinoid CB1 receptors. This neuroprotective effect is relevant for inflammatory brain conditions like Alzheimer's disease.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Neuroinflammation
Background:
- Tumor necrosis factor alpha (TNFα) modulates synaptic transmission and plasticity in the central nervous system.
- TNFα is upregulated during injury and infection, potentially causing neuronal death via excessive calcium influx through AMPA receptors.
- This highlights a critical role for TNFα in neuroinflammatory processes.
Purpose of the Study:
- To investigate the neuroprotective effects of adult neural stem cells (aNPCs) on TNFα-induced neuronal hyperexcitation.
- To elucidate the mechanisms underlying aNPC-mediated neuroprotection.
- To explore the therapeutic potential of aNPCs in neuroinflammatory diseases.
Main Methods:
- Primary cortical neuron cultures from E18 foetal mice were utilized.
- Neurons were co-incubated with either unstimulated or LPS-stimulated aNPCs.
- Electrophysiological recordings assessed neuronal transmission following TNFα treatment.
Main Results:
- aNPCs, particularly those from the subventricular zone, reversed TNFα-induced excitatory neurotransmission potentiation.
- This neuroprotective effect was mediated by the activation of cannabinoid CB1 receptors.
- aNPCs demonstrated a significant role in mitigating TNFα-induced neuronal hyperexcitation.
Conclusions:
- aNPCs can prevent TNFα-induced excitatory neurotransmission potentiation in cortical neurons.
- Cannabinoid CB1 receptor activation is a key mechanism in aNPC-mediated neuroprotection.
- These findings suggest therapeutic potential for aNPCs in inflammatory conditions affecting the cortex, such as Alzheimer's disease.
