Background: Motor neuron disease is characterised by neuroinflammation, toxic protein aggregate formation, and the degeneration of discrete populations of motor neurons in the spinal cord. Thus, it is important to investigate regional differences in the cells that comprise the central nervous system and support motor neuron health to understand why spinal cord motor neurons specifically degenerate over other cell types in the brain.
Aim: Since the downstream products of heat shock response induction (e.g. Hsp27) have anti-aggregation and anti-apoptotic activities, we sought to investigate differences in the ability of cortical versus spinal cord astroglial primary cells to mount a heat shock response in response to various inducers of cellular stress.
Results: We show by flow cytometry that double the number of spinal cord astrocytes were Hsp27 positive compared to cortical astrocytes under basal conditions. Furthermore, spinal cord astrocytes were responsive to heat shock, whereas cortical astrocytes were not. However, neither spinal cord nor cortical astrocytes upregulated Hsp27 expression after treatment with LPS or TNFα (inflammatory mediators).
Significance and conclusions: Combined, this data shows that the spinal cord possesses a higher proportion of Hsp27 positive astrocytes compared to cortical astrocytes. This may provide greater anti-aggregation and anti-apoptotic support to motor neurons of the spinal cord. Further research comparing the heat shock responses in cortical and spinal cord cultures derived from an MND mouse model are required to determine whether regional differences in glia affect the vulnerability of motor neurons to degeneration in MND.