Examining the implications of astrocyte heterogeneity across the brain and spinal cord

Aug. 21, 2018

Astrocytes have been identified as important components in regulating function and how the body responds to brain and spinal cord injuries. Prior research has provided evidence of cytoarchitectural and functional specialization that occurs throughout the central nervous system (CNS). This fact led Mayo researchers recently to take a closer look at astrocyte heterogeneity across the different regions of the CNS and at all stages of development, and to better understand the extent of these differences.

In a study published in PLOS One in July 2017, Mayo researchers compared the expression of key astroglial markers — glial fibrillary acidic protein (GFAP) and aldehyde dehydrogenase-1 family member L1 (ALDH1L1) — across different regions of the neuraxis, and tracked their expression at different developmental stages and in the context of demyelination. Mayo researchers also recorded any changes in the astrocyte regulatory cytokine interleukin 6 (IL-6), and its signaling partner signal transducer and activator of transcription 3 (STAT3), in vivo and in vitro.

The Mayo Clinic study yielded several interesting results:

  • GFAP and IL-6 levels are higher in astrocytes found in the developing and adult spinal cord than in brain-derived astrocytes.
  • Toxin-mediated demyelination elicits more GFAP reactivity in the spinal cord than in the brain.
  • Astrocytes appear earlier in the developing spinal cord than in the brain.
  • Spinal cord astrocytes express higher levels of GFAP in adulthood than do brain-derived astrocytes.
  • Spinal cord astrocytes express higher levels of IL-6 and STAT3 than do brain-derived astrocytes.
  • GFAP reactivity is also greater in the spinal cord than in the brain after focal demyelinating injury.

These findings have several key implications. "Because astrocytes appear to be key regulators of essential physiological functions in the CNS and its response to injury and disease, we need to develop a deeper understanding of any regional differences in these cells," explains Isobel A. Scarisbrick, Ph.D., director of the Neuroregeneration and Neurorehabilitation Laboratory at Mayo Clinic's campus in Minnesota and the study's principal investigator.

"Our findings suggest that the quantity of astrocytes and the expression of GFAP and IL-6 differ, depending on whether they are derived from the spinal cord or the brain," says Dr. Scarisbrick. "And these differences, which are also associated with regional and developmental specialization, could have a significant impact on how different regions of the central nervous system respond to injury and disease."

Dr. Scarisbrick's lab studies how astrocyte and oligodendrocyte metabolic activities are altered in CNS injury and disease, and how this impacts nerve function and the capacity for regenerative repair. "Because astrocyte heterogeneity affects how the brain and spinal cord respond to injury and disease, future research focused on the design of targeted therapies needs to take these differences into account," she says.

For more information

Yoon H, et al. Astrocyte heterogeneity across the brain and spinal cord occurs developmentally, in adulthood and in response to demyelination. PLOS One. 12:e0180697.