title: Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons.
abstract: Human hGDH2 arose via duplication in the apes and driven by positive selection acquired enhanced catalytic ability under conditions inhibitory to its precursor hGDH1 (common to all mammals). To explore the biological advantage provided by the novel enzyme, we studied, by immunohistochemistry (IHC) and immunofluorescence (IF), hGDH1 and hGDH2 expression in the human brain. Studies on human cortical tissue using anti-hGDH1-specific antibody revealed that hGDH1 was expressed in glial cells (astrocytes, oligodendrocytes, and oligodendrocyte precursors) with neurons being devoid of hGDH1 staining. In contrast, an hGDH2-specific antiserum labeled both astrocytes and neurons. Specifically, hGDH2 immunoreactivity was found in the cytoplasm of large neuronal cells within coarse structures resembling mitochondria. These were distributed either in the perikaryon or in the cell periphery. Double immunofluorescence (IF) suggested that the latter represented hGDH2-labeled mitochondria of presynaptic nerve terminals. Hence, hGDH2 evolution bestowed large human neurons with enhanced glutamate metabolizing capacity, thus strengthening cortical excitatory transmission.
authors.affiliation: Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Crete, Heraklion, Crete, Greece. kliospanaki@gmail.com.|Faculty of Medicine, School of Health Sciences, University of Crete, Voutes, 71003, Heraklion, Crete, Greece. kliospanaki@gmail.com.
authors.forename: Cleanthe
authors.initials: C
authors.lastname: Spanaki
authors.affiliation: Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Crete, Heraklion, Crete, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Kotzamani
authors.affiliation: Neuroscience Laboratory and Neurology Clinics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Kleopas
authors.initials: K
authors.lastname: Kleopa
authors.affiliation: Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Crete, Heraklion, Crete, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Plaitakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001253:Astrocytes / Q000201:enzymology; D037281:Calnexin / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology*; D019143:Evolution, Molecular; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology*
chemical_list: D037281:Calnexin; D005969:Glutamate Dehydrogenase; C561840:GLUD1 protein, human; C521120:GLUD2 protein, human
keywords: Human brain; Neuron glial cells; hGDH1; hGDH2