title: Hippocampal distribution of vesicular glutamate transporter 1 in patients with temporal lobe epilepsy.
abstract: OBJECTIVE
  Vesicular glutamate transporters (VGLUTs) are responsible for loading synaptic vesicles with glutamate, determining the phenotype of glutamatergic neurons, and have been implicated in the regulation of quantal size and presynaptic plasticity. We analyzed VGLUT subtype expression in normal human hippocampus and tested the hypothesis that alterations in VGLUT expression may contribute to long-term changes in glutamatergic transmission reported in patients with temporal lobe epilepsy (TLE).
  
  
  METHODS
  VGLUT immunohistochemistry, immunofluorescence, in situ hybridization, Western blotting, and quantitative polymerase chain reaction (qPCR) were performed on biopsies from TLE patients without (non-HS) and with hippocampal sclerosis (HS) and compared to autopsy controls and rat hippocampus. VGLUT1 expression was compared with synaptophysin, neuropeptide Y (NPY), and Timm's staining.
  
  
  RESULTS
  VGLUT1 was the predominant VGLUT in human hippocampus and appeared to be localized to presynaptic glutamatergic terminals. In non-HS hippocampi, VGLUT1 protein levels were increased compared to control and HS hippocampi in all subfields. In HS hippocampi VGLUT1 expression was decreased in subfields with severe neuronal loss, but strongly up-regulated in the dentate gyrus, characterized by mossy fiber sprouting.
  
  
  CONCLUSIONS
  VGLUT1 is used as marker for glutamatergic synapses in the human hippocampus. In HS hippocampi VGLUT1 up-regulation in the dentate gyrus probably marks new glutamatergic synapses formed by mossy fiber sprouting. Our data indicate that non-HS patients have an increased capacity to store glutamate in vesicles, most likely due to an increase in translational processes or upregulation of VGLUT1 in synapses from afferent neurons outside the hippocampus. This up-regulation may increase glutamatergic transmission, and thus contribute to increased extracellular glutamate levels and hyperexcitability.
authors.affiliation: Department of Neuroscience & Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. w.s.vanderhel@umcutrecht.nl
authors.forename: W Saskia
authors.initials: WS
authors.lastname: van der Hel
authors.forename: Suzanne A M W
authors.initials: SA
authors.lastname: Verlinde
authors.forename: Dimphna H M
authors.initials: DH
authors.lastname: Meijer
authors.forename: Marina
authors.initials: M
authors.lastname: de Wit
authors.forename: Marije G
authors.initials: MG
authors.lastname: Rensen
authors.forename: Koen L I
authors.initials: KL
authors.lastname: van Gassen
authors.forename: Peter C
authors.initials: PC
authors.lastname: van Rijen
authors.forename: Cees W M
authors.initials: CW
authors.lastname: van Veelen
authors.forename: Pierre N E
authors.initials: PN
authors.lastname: de Graan
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D012598:Sclerosis / Q000473:pathology; D013569:Synapses / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism; D014018:Tissue Distribution; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism* / Q000502:physiology
chemical_list: D009478:Neuropeptide Y; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid