Increased Cortical Expression of Two Synaptogenic Thrombospondins in Human Brain Evolution

Thrombospondins are extracellular-matrix glycoproteins implicated in the control of synaptogenesis and neurite growth. Previous microarray studies suggested that one gene of this family, thrombospondin 4 (THBS4), was upregulated during human brain evolution. Using independent techniques to examine t...

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Bibliographic Details
Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2007-10, Vol.17 (10), p.2312-2321
Main Authors: Cáceres, Mario, Suwyn, Carolyn, Maddox, Marcelia, Thomas, James W., Preuss, Todd M.
Format: Article
Language:English
Subjects:
Adult
Animals
Brain - physiology
Cerebral Cortex - physiology
Evolution, Molecular
gene expression
Gene Expression Regulation
human evolution
Humans
In Situ Hybridization
Macaca
neuroanatomy
Pan troglodytes
plasticity
Primates
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
synaptogenesis
Thrombospondins - genetics
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Summary:Thrombospondins are extracellular-matrix glycoproteins implicated in the control of synaptogenesis and neurite growth. Previous microarray studies suggested that one gene of this family, thrombospondin 4 (THBS4), was upregulated during human brain evolution. Using independent techniques to examine thrombospondin expression patterns in adult brain samples, we report ∼6-fold and ∼2-fold greater expression of THBS4 and THBS2 messenger RNA (mRNA), respectively, in human cerebral cortex compared with chimpanzees and macaques, with corresponding differences in protein levels. In humans and chimpanzees, thrombospondin expression differences were observed in the forebrain (cortex and caudate), whereas the cerebellum and most nonbrain tissues exhibited similar levels of the 2 mRNAs. Histological examination revealed THBS4 mRNA and protein expression in numerous pyramidal and glial cells in the 3 species but humans also exhibited very prominent immunostaining of the synapse-rich cortical neuropil. In humans, additionally, THBS4 antibodies labeled β-amyloid containing plaques in Alzheimer's cases and some control cases. This is the first detailed characterization of gene-expression changes in human evolution that involve specific brain regions, including portions of cerebral cortex. Increased expression of thrombospondins in human brain evolution could result in changes in synaptic organization and plasticity, and contribute to the distinctive cognitive abilities of humans, as well as to our unique vulnerability to neurodegenerative disease.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bhl140