ANALYSIS OF HIPPOCAMPAL NEURONS AND GLIA IN THE EPILEPITIC EL MOUSE
Abstract number :
3.072
Submission category :
Year :
2002
Submission ID :
1368
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Michael G. Drage, Gregory L. Holmes, Thomas N. Seyfried. Biology, Boston College, Chestnut Hill, MA; Neurology, Harvard Medical School, Children[ssquote]s Hospital, Boston, MA
RATIONALE: The epileptic EL mouse is a genetic model for complex partial seizures with secondary generalization. There is controversy whether brief, recurrent seizures result in progressive neuronal loss and synaptic reorganization. In this study, we evaluated neuronal number, mossy fiber organization, and astrocytosis in the hippocampus of epileptic EL mice.
METHODS: Epileptic EL mice (n = 6 independent mice) were compared with non-epileptic DDY (n = 4) and B6 (n = 5) mice at adult ([gt]1 yr) ages. The EL mice experienced about 25-30 handling induced seizures by this age. All analyses were performed on 30 [mu]m cryostat sections. An optical fractionator method was used to count Nissl stained neurons in the hilus, CA1, and CA3 regions of the hippocampus. Infrapyramidal mossy fiber organization was analyzed using the Timm silver stain and was scored using a semi-quantitative scale. The distribution of astrocytes was examined using an antibody specific for glial fibrillary acidic protein (GFAP).
RESULTS: Timm Scores in the CA3 hippocampal region of the B6, DDY, and EL mice were 0.8 [plusminus] 0.2, 0.1 [plusminus] 0.1, 0.2 [plusminus] 0.1, respectively; and in the CA1 region were 1.1 [plusminus] 0.1, 1.5 [plusminus] 0.7, 1.5 [plusminus] 0.3, respectively. The number of neurons in these strains was 166 [plusminus] 25, 152 [plusminus] 18, and 179 [plusminus] 11 for the hilus; 634 [plusminus] 41, 644 [plusminus] 80, 612 [plusminus] 33 for the CA1 region, and 548 [plusminus] 45, 761 [plusminus] 120, 645 [plusminus] 44 for the CA3 region, respectively. None of the observed differences were significant between the EL and nonepileptic control strains. However, the number of hippocampal GFAP positive astrocytes was significantly higher (p [lt] 0.05) in the EL than in the B6 and DDY mice.
CONCLUSIONS: These results support previous studies indicating that seizure susceptibility and seizures in EL mice are not associated with hippocampal neuronal loss, despite the presence of a significant astrocytosis. These results also suggest that neuronal loss may be necessary for aberrant mossy fiber synaptic reorganization. The EL mouse is a good model of multifactorial idiopathic epilepsy.
[Supported by: NIH grants HD39722 (TNS) and NS27984 (GLH).]