MicroRNA expression patterns in human astrocytes in relation to anatomical location and age.
Abstract
Anatomic distribution and age are variables linked to functions of astrocytes under physiologic and pathologic conditions. We measured the relative expression of a panel of microRNAs (miRNAs) in astrocytes captured by laser micro-dissection from normal human adult white and grey matter, human fetal white matter and germinal matrix samples. Although expression of most miRNAs was comparable between adult and fetal samples, regional differences were observed. In the adult cerebral cortex, expression of miRNAs in morphologically distinct inter-laminar astrocytes underlying the glial limitans differed from those in deeper cortical layers, suggesting functional specialization possibly related to structural stability and defense from potentially harmful factors in the cerebrospinal fluid. Differences between adult white and grey matter miRNA expression included higher expression of pro-inflammatory miRNAs in the former, potentially contributing to differences in inflammation between grey and white matter plaques in multiple sclerosis. Lower expression of miRNAs in fetal versus adult white matter astrocytes likely reflects the immaturity of these migrating cells. Highly expressed miRNAs in the fetal germinal matrix are probably relevant in development and also recapitulate some responses to injury. Future studies can address regional alterations of miRNA expression in pathological conditions.
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The low expression of miR-34a in ILAs is probably linked to their stability, and the low expression of miR-449 is linked to their typical architecture.
“For instance, the low expression of miR-34a (which induces astrogliogenesis) is probably linked to the stability of ILA; while the low expression of miR-449 (a regulator of microtubule dynamics in cell proliferation) is linked to their typical architecture.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Rao et al. (2016)
ILAs show an abundance of anti-inflammatory miRNA (such as miR-146, with limited expression of pro-inflammatory miR-338 and miR-365) and modulators of GFAP expression (such as miR-125b), supporting the hypothesis of ILAs as a "first-line defense" against external insults.
“On the contrary, there was an abundance of anti-inflammatory miRNA (as miR-146, which coincides with the limited expression of pro-inflammatory miR-338 and miR-365) and modulators of GFAP expression (as miR-125b), supporting the hypothesis of ILA as a “first-line defense” against external insults (Rao et al., 2016).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Rao et al., 2016
ILAs show low or undetectable expression of miRNA-regulating genes linked to cell proliferation, development, migration, angiogenesis, and pro-inflammatory processes.
“There was a low or undetectable expression of miRNA-regulating genes linked to cell proliferation, development, migration, angiogenesis, and pro-inflammatory processes, suggesting high stability of these cells, which do not appear deeply involved in metabolic homeostasis.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Rao et al. (2016)
ILAs have an expression profile distinct from other astrocytes, indicating more specific and restrictive roles.
“This analysis revealed that ILAs have an expression profile distinct from other astrocytes, indicating more specific and restrictive roles.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Rao et al. (2016)
ILAs have a unique microRNA expression profile compared to protoplasmic and fibrous astrocytes.
“ILAs were found to have a unique miRNA profile compared to the protoplasmic and fibrous astrocytes.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Rao et al. (2016)
The 20 oligodendrocyte-enriched miRs included hsa-miR-219a, hsa-miR-338, and hsa-miR-23.
“Notably, these included hsa-miR-219a and hsa-miR-338, both known to promote myelin repair 54 , and hsa-miR-23, which enhances oligodendrocyte differentiation and myelin synthesis 55 .”
From Human brain microRNAs exhibit cell-type specificity and age dependence (2026) · cites this paper as [55]
hsa-miR-219a and hsa-miR-338 are known to promote myelin repair, and hsa-miR-23 enhances oligodendrocyte differentiation and myelin synthesis.
“both known to promote myelin repair 54 , and hsa-miR-23, which enhances oligodendrocyte differentiation and myelin synthesis 55”
From Human brain microRNAs exhibit cell-type specificity and age dependence (2026) · cites this paper as [55]
Cites
Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E., & Ambros, V. (2004) · Genome Biology · doi:10.1186/gb-2004-5-3-r13 · Cited by 1,578 · see citing works
MicroRNA-146a: A Key Regulator of Astrocyte-Mediated Inflammatory Response
Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W. G. M., van Rijen, P. C., Gorter, J. A., & Aronica, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044789 · Cited by 330 · see citing works
miR‐155 as a multiple sclerosis–relevant regulator of myeloid cell polarization
Moore, C. S., Rao, V. T. S., Durafourt, B. A., Bedell, B. J., Ludwin, S. K., Bar‐Or, A., & Antel, J. P. (2013) · Annals of Neurology · doi:10.1002/ana.23967 · Cited by 219 · cited 1× · see citing works
“cDNAs from laser-captured samples were subjected to a pre-amplification reaction using a pooled set of TaqManVR miRNA-specific probes to increase the number of target copies, as previously described for lasercaptured FFPE samples (11, 12).”
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Functional diversity of astrocytes in neural circuit regulation
Haim, L. B., & Rowitch, D. H. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.159 · Cited by 618 · see citing works
Chronic inflammation in multiple sclerosis - seeing what was always there
Matthews, P. M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0240-y · Cited by 128 · see citing works
Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain
Ciani, C., & Falcone, C. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1477753 · Cited by 11 · see citing works
Human brain microRNAs exhibit cell-type specificity and age dependence
Dubnov, S., Laski, L., Zchut, I., Avidan, O., Bennett, E. R., Greenberg, D. S., Turjeman, A., Nitzan, M., Paldor, I., & Soreq, H. (2026) · doi:10.64898/2026.01.04.697535
- Authors
- Rao, V. T. S., Ludwin, S. K., Fuh, S.-C., Sawaya, R., Moore, C. S., Ho, M.-K., Bedell, B. J., Sarnat, H. B., Bar-Or, A., & Antel, J. P.
- Affiliations
- McGill University (CA)
- Montreal Neurological Institute and Hospital (CA)
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-01-22
- Volume
- 75
- Issue
- 2
- Pages
- 156-166
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2255875670
- Cited by
- 50
- References
- 3
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 11 · 2021: 2 · 2020: 5 · 2019: 9 · 2018: 5 · 2017: 3 · 2016: 5
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microRNA expression, astrocytes, cerebral cortex, white matter, grey matter, germinal matrix, fetal brain, age-related changes, multiple sclerosis, neuroinflammation, astrocyte migration, brain development
- MeSH terms
- Adult, Aged, Aging, Astrocytes, Female, Fetus, Glial Fibrillary Acidic Protein, Humans, Inflammation, Middle Aged, Pregnancy, Gene Expression Profiling, MicroRNAs, Young Adult, White Matter, Gray Matter
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