Title:Metabotropic Glutamate Receptor 5 in Down's Syndrome Hippocampus During Development: Increased Expression in Astrocytes
Volume: 11
Issue: 7
Author(s): A.M. Iyer, J. van Scheppingen, I. Milenkovic, J.J. Anink, D. Lim, A.A. Genazzani, H. Adle-Biassette, G. G. Kovacs and E. Aronica
Affiliation:
Keywords:
Alzheimer's disease, astrocytes, development, Down's syndrome, hippocampus, mGluR5.
Abstract: Metabotropic glutamate receptor 5 (mGluR5) is highly expressed throughout the forebrain and hippocampus.
Several lines of evidence support the role of this receptor in brain development and developmental disorders, as well as in
neurodegenerative disorders like Alzheimer’s disease (AD). In the present study, the expression pattern of mGluR5 was
investigated by immunocytochemistry in the developing hippocampus from patients with Down's syndrome (DS) and in
adults with DS and AD. mGluR5 was expressed in developing human hippocampus from the earliest stages tested (9 gestational
weeks), with strong expression in the ventricular/subventricular zones. We observed a consistent similar temporal
and spatial neuronal pattern of expression in DS hippocampus. However, in DS we detected increased prenatal mGluR5
expression in white matter astrocytes, which persisted postnatally. In addition, in adult DS patients with widespread ADassociated
neurodegeneration (DS-AD) increased mGluR5 expression was detected in astrocytes around amyloid plaque.
In vitro data confirm the existence of a modulatory crosstalk between amyloid-β and mGluR5 in human astrocytes. These
findings demonstrate a developmental regulation of mGluR5 in human hippocampus and suggest a role for this receptor in
astrocytes during early development in DS hippocampus, as well as a potential contribution to the pathogenesis of ADassociated
pathology.
