TY - JOUR
T1 - Cholinergic sprouting in the hippocampus
T2 - A proposed role for IL-1
AU - Fagan, Anne M.
AU - Gage, Fred H.
N1 - Funding Information:
We thank Drs. L. Eng and E. Johnson for their kind gifts of the GFAP and NGF-receptor antibodies, Steve Forbes and Donna Chin for their technical assistance, Sheryl Christenson for help in organizing the manuscript, and Drs. G. Higgins and M. Schinstine for their helpful comments. This research was supported by grants from the Office of Naval Research and PHS NS28121-01.
PY - 1990/10
Y1 - 1990/10
N2 - Damage to the entorhinal afferents (i.e., perforant path) to the hippocampal dentate gyrus leads to sprouting of the remaining intact septal cholinergic afferents within the denervated outer molecular layer. To investigate the cellular and molecular events which may contribute to this sprouting response, we describe the temporal sequence of cellular changes in the denervated zone prior to the observed neural reorganization. Rats were given perforant path (PP) transections and sacrificed at various time points following the lesion, on Days (D) 1, 2, 3, 4, 5, 6, and 30. Coronal sections at the level of the dorsal hippocampus were immunostained to localize microglia (OX-42), interleukin-1 (IL-1), and astroctytes (GFAP). We observed a rapid increase in the number of immunoreactive microglia in the denervated molecular layer within the first day following PP transection. Parallel sections show a concomitant increase in the number of IL-1-positive cells. Maximal reactive changes (i.e., hypertrophy and increase in number) in GFAP-positive astrocytes are not observed until D5. This time course of events suggests a role of microglia in astrocyte activation in vivo via production of IL-1 and offers support for a proposed hypothesis postulating a cascade of glial events which may lead to cholinergic sprouting following PP transection.
AB - Damage to the entorhinal afferents (i.e., perforant path) to the hippocampal dentate gyrus leads to sprouting of the remaining intact septal cholinergic afferents within the denervated outer molecular layer. To investigate the cellular and molecular events which may contribute to this sprouting response, we describe the temporal sequence of cellular changes in the denervated zone prior to the observed neural reorganization. Rats were given perforant path (PP) transections and sacrificed at various time points following the lesion, on Days (D) 1, 2, 3, 4, 5, 6, and 30. Coronal sections at the level of the dorsal hippocampus were immunostained to localize microglia (OX-42), interleukin-1 (IL-1), and astroctytes (GFAP). We observed a rapid increase in the number of immunoreactive microglia in the denervated molecular layer within the first day following PP transection. Parallel sections show a concomitant increase in the number of IL-1-positive cells. Maximal reactive changes (i.e., hypertrophy and increase in number) in GFAP-positive astrocytes are not observed until D5. This time course of events suggests a role of microglia in astrocyte activation in vivo via production of IL-1 and offers support for a proposed hypothesis postulating a cascade of glial events which may lead to cholinergic sprouting following PP transection.
UR - http://www.scopus.com/inward/record.url?scp=0025104109&partnerID=8YFLogxK
U2 - 10.1016/0014-4886(90)90055-W
DO - 10.1016/0014-4886(90)90055-W
M3 - Article
C2 - 1698653
AN - SCOPUS:0025104109
SN - 0014-4886
VL - 110
SP - 105
EP - 120
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -