Increased cortical expression of two synaptogenic thrombospondins in human brain evolution.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Cáceres, Mario; Suwyn, Carolyn; Maddox, Marcelia; Thomas, James W; Preuss, Todd M
Year of Publication: 2007
Journal: Cereb Cortex
Volume: 17
Issue: 10
Pagination: 2312-21
Date Published: 2007 Oct
Publication Language: eng
ISSN: 1047-3211
Keywords: Adult, Animals, Brain, Cerebral Cortex, Evolution, Molecular, Gene Expression Regulation, Humans, In Situ Hybridization, Macaca, Pan troglodytes, Primates, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Thrombospondins

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 approximately 6-fold and approximately 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 beta-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.

DOI: 10.1093/cercor/bhl140
Alternate Journal: Cereb. Cortex