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Biochemical Society & British Neuroscience Association Focused Meeting: Astrocytes in Health and Neurodegenerative Disease

Prof Siddharthan Chandran (left)
Prof Siddharthan Chandran (left)

The meeting covered multiple aspects of astrocyte biology, including sessions on Astrocyte-Neuron Interactions, Energy Metabolism and Astrocytes, Astrocyte Signalling Pathways, and individual sessions on the role of astrocytes in Motor Neurone Disease, Alzheimer’s Disease and Lysosomal Storage Disorders.

The Contribution of Astrocytes to Motor Neurone Disease session was opened by Siddharthan Chandran (University of Edinburgh), who emphasised how MND was now viewed as a CNS disease, rather than just a disease of the motor neurons. He summarised the evidence of astrocytic involvement in MND, including reporting on how iPSC-derived astrocytes derived from TARDBP mutant fibroblasts behave the same as wild type in relation to synaptogenesis and glutamate uptake, but accumulated TDP-43 in the cytoplasm, recapitulating the phenotype seen in disease.

Laura Ferraiuolo (Nationwide Children’s Hospital, Columbus) then reported on how neural progenitor cells (NPCs) can be obtained from the human spinal cord post-mortem and differentiated into neurons, astrocytes and oligogendrocytes. Fibroblasts were also used to generate NPCs and subsequently astrocytes, thereby increasing the number of patient samples available. Using a 3 week protocol, they demonstrated that astrocytes from SOD1, TARDBP and C9orf72 patients were toxic to motor neurons.

The final talk of the session was from Akshata Ahnad (John Hopkins University), who discussed the potential for astrocytes as a cell replacement therapy. Using iPSC-derived astrocytes from control, SOD1 and C9orf72-related ALS fibroblasts, they injected astrocytes into a rat model of ALS. The astrocytes survived in the spinal cord and work is ongoing to assess the effect of the normal and mutant astrocytes on survival of the rats.

Other highlights included Alexei Verkhratsky’s (University of Manchester) excellent overview of astroglia in health and disease, Nicola Allen (Salk Institute) discussing how astrocyte secretion of glypican proteins recruit AMPA glutamate receptors to form excitatory synapses during development, whilst Pierre Magistretti (BESE-KAUST & BMI_EPFL) discussed the role of lactate in glutamate signalling and calcium influx in astrocytes.

In addition, in contrast to ALS, in Alzheimer’s disease (AD) Amy Birch (Imperial College London) described how a reduction in astrocyte proliferation in the APP23 mouse model of AD led to increased beta-amyloid, an increase in the rate of memory decline and an increased error rate in the Y-maze memory task.

Finally, Milos Pekny demonstrated how growing astrocytes in 3D, using a nanofibre skeleton for support, generated far more complex cells than those grown in the standard tissue culture dish. Is this the future for astrocyte cell culture?

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