Alterations in hippocampal voltage-gated calcium channel alpha 1 subunit expression patterns after kainate-induced status epilepticus in aging rats.
Young adult and aged male Fisher 344 rats underwent kainate-induced convulsive status epilepticus (SE) for 4 h prior to sacrifice to determine potential aging-related differences in the effect of prolonged SE on the expression of hippocampal voltage-gated calcium channels (VGCCs). Immunohistochemistry was performed on hippocampal sections using antibodies directed against the alpha1 subunit of class A-D VGCCs. Compared to age-matched controls, SE animals showed a marked loss of alpha1A immunoreactivity (IR) in CA3 and the hilus, which was more prominent in aged animals. Alpha1B-IR was decreased selectively in the stratum lucidum of CA3. Alpha1C-IR was increased on neuronal somata in the pyramidal and granule cell layers of both age groups. In contrast, there was a marked decrease of alpha1C-IR in the neuropil of CA3 stratum pyramidale and portions of CA1, which was more pronounced in aged animals. Alpha1D-IR was decreased in CA3 and the hilus, which was more prominent in aged animals. Nissl staining demonstrated mild somal dysmorphia in the pyramidal cell layer of CA3, which was more apparent in aged animals. Fluoro-Jade B staining was prominent in the stratum pyramidale of CA3 and in the hilus of aged SE animals. These results demonstrated that expression patterns of hippocampal high-threshold VGCC alpha1 subunits were altered variably during prolonged convulsive SE and were associated with prominent early degenerative changes in aged neurons in CA3 and the hilus.
Kelly
Kevin M
KM
Department of Neurology, Allegheny-Singer Research Institute, Allegheny General Hospital, 940 South Tower, 320 E North Avenue, Pittsburgh, PA 15212-4772, USA. kelly@wpahs.org
Ikonomovic
Milos D
MD
Abrahamson
Eric E
EE
Kharlamov
Elena A
EA
Hentosz
Teresa M
TM
Armstrong
David M
DM
D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D021122:Protein Subunits / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*
C498917:Cacna1e protein, rat; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D007608:Kainic Acid