GRANULE CELL DISPERSION IN MTLE IS ASSOCIATED WITH MOLECULAR LAYER ASTROGLIAL PROLIFERATION
Abstract number :
3.013
Submission category :
Year :
2005
Submission ID :
5819
Source :
www.aesnet.org
Presentation date :
12/3/2005 12:00:00 AM
Published date :
Dec 2, 2005, 06:00 AM
Authors :
Alexander A. Sosunov, Xiaoping Wu, Robert R. Goodman, and Guy M. McKhann II
Granule cell (GC) dispersion (GCD) is a prominent feature of hippocampal sclerosis (HS) in MTLE. Despite abundant information on GCD, data regarding the accompanying changes in glial cells is lacking. We performed immunohistochemical and ultrastructural investigations of glial cells and dentate granule cells in the hippocampus in resected MTLE and autopsy control samples. GCD was observed in the majority of HS cases (83 % of 42 cases), while depletion of GC (26 %) and bilamination of GC (14 %) were detected less frequently. Abnormal GC morphology was commonly observed in focal areas in the dentate fascia, with dispersion, bilamination, and areas of GC depletion often seen within the same hippocampus. Based on confocal microscopy, astrocytes in the molecular layer of dentate gyri with GCD were frequently found in multicellular aggregates of 2-6 cells that were often distributed in a radial manner. Comparison of confocal and electron microscopic data distinguished these cellular aggregates, with both multinucleated cells and tightly packed groups of cells present. The amount of these cell aggregates was significantly (p[lt]0.001) higher in HS vs. non-HS (n = 16) MTLE cases, and in non-HS cases vs. autopsy controls (n = 6). Areas with GC depletion did not demonstrate increased astrocyte aggregation..
In two thirds of cases of GCD, reactive astrocytes were found in the molecular layer. Reactive astrocytes were characterized by a large cell body size and high expression of GFAP, vimentin, and , less commonly, nestin. Some reactive astrocytes contained two or three nuclei. In histologically [ldquo]normal[rdquo] areas of MTLE (preserved CA1 subfields or prosubiculum), astrocyte doublets were more frequently detected in epileptic (HS or non-HS) tissue, in comparison with autopsy controls. GCD is associated with an increase in molecular layer astrogliogenesis. We hypothesize that some reactive astrocytes undergo mitosis without cytokinesis. We are investigating whether adult human astrocytes require conversion to reactive astrocytes to undergo cellular division. (Supported by NIH (R21, K08)
Klingenstein Foundation
New York Academy of Medicine.)