Human-specific features of cerebellar astrocytes and Purkinje cells: an anatomical comparison with mice and macaques
Little is known about the morphological diversity and distribution of cerebellar astrocytes in the human brain and how or if these features differ from those of cerebellar astrocytes in species used to model human illnesses. To address this, we performed a comparative post-mortem examination of cerebellar astrocytes and Purkinje cells (PCs) in healthy humans, macaques, and mice using microscopy-based techniques. Visualizing with canonical astrocyte markers glial fibrillary acidic protein (GFAP) and aldehyde dehydrogenase-1 family member L1 (ALDH1L1), we mapped astrocytes within a complete cerebellar hemisphere. Astrocytes were observed to be differentially distributed across the cerebellar layers, displayed overall increases in area coverages with evolution, and showed features uniquely hominoid. Stereological quantifications in 3 functionally distinct cerebellar lobules demonstrated opposing trends for the canonical astrocyte markers across species with ALDH1L1+ astrocytes increasing with evolution and GFAP+ astrocytes decreasing. PC analyses revealed that while humans have the lowest PC densities, their cell body sizes were the largest with more ALDH1L1 immunoreactive astrocytes surrounding. Notably, the cognitive lobule crus I displayed the highest ratio of Bergmann glia to PC in all species. These findings align with the growing literature for astrocyte and PC heterogeneity and suggest cerebellar astrocyte and PC divergence both within and across species, possibly indicative of a role for these cells in higher-order cerebellar processing.



O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/607849v1_ufig1.gif" ALT="Figure 1">
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org.highwire.dtl.DTLVardef@1bfbf0borg.highwire.dtl.DTLVardef@1977861org.highwire.dtl.DTLVardef@16067aborg.highwire.dtl.DTLVardef@361683_HPS_FORMAT_FIGEXP M_FIG C_FIG Main PointsO_LIALDH1L1 and GFAP immunoreactive astrocytes are differentially distributed across cerebellar layers and lobules.
C_LIO_LIOpposing trends across species with ALDH1L1+ astrocyte densities increasing and GFAP+ astrocyte densities decreasing with larger cerebella.
C_LIO_LIWith evolution, Purkinje cell densities decrease while their cell bodies and the number of Bergmann glia surrounding increase.
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