TY - JOUR
T1 - Rapid alterations in dendrite morphology during sublethal hypoxia or glutamate receptor activation
AU - Park, James S.
AU - Bateman, Michael C.
AU - Goldberg, Mark P.
N1 - Funding Information:
We thank Jennifer Freeman, Jeannie David, and Sandy Althom-sons for expert technical assistance, and John Olney, Dennis Choi, and Laura Dugan for helpful early discussion. David Holtzman and John McDonald provided critical review of the manuscript. Supported by grants (to M.P.G.) from the Brain Trauma Foundation and NIH (NS01543 and NS32140). J.S.P. was supported by a Developmental Neurology Training grant (NS07027). This work was done during the tenure of a Grant-in-Aid Award (to M.P.G.) from the American Heart Association and William Randolph Hearst Foundation.
PY - 1996/6
Y1 - 1996/6
N2 - Selective degeneration of postsynaptic neuronal dendrites is a pathological hallmark of brain injury in stroke and other neurological disorders. We examined dendritic injury in primary cultures dissociated from mouse neocortex. Neuronal morphology was visualized using the fluorescent membrane tracer, DiI, or immunofluorescence with antibodies to the dendrite- specific microtubule-associated protein, MAP2. Deprivation of oxygen and glucose for 30-60 min resulted in segmental dendritic beading, or varicosities, and loss of dendritic spines. This pattern of dendritic injury was blocked by addition of selective NMDA antagonists, and was reproduced within 5 min of exposure to 10-100 μM NMDA. Widespread dendritic varicosity formation occurred even with exposures to oxygen-glucose deprivation or NMDA which resulted in little neuronal death by the following day. Despite marked structural changes affecting virtually all neurons, dendrite shape returned to normal within 2 h of terminating sublethal oxygen-glucose deprivation or NMDA application. Rapid, reversible changes in dendritic structure may contribute to alterations in neuronal function following glutamate receptor stimulation under physiological or pathological conditions.
AB - Selective degeneration of postsynaptic neuronal dendrites is a pathological hallmark of brain injury in stroke and other neurological disorders. We examined dendritic injury in primary cultures dissociated from mouse neocortex. Neuronal morphology was visualized using the fluorescent membrane tracer, DiI, or immunofluorescence with antibodies to the dendrite- specific microtubule-associated protein, MAP2. Deprivation of oxygen and glucose for 30-60 min resulted in segmental dendritic beading, or varicosities, and loss of dendritic spines. This pattern of dendritic injury was blocked by addition of selective NMDA antagonists, and was reproduced within 5 min of exposure to 10-100 μM NMDA. Widespread dendritic varicosity formation occurred even with exposures to oxygen-glucose deprivation or NMDA which resulted in little neuronal death by the following day. Despite marked structural changes affecting virtually all neurons, dendrite shape returned to normal within 2 h of terminating sublethal oxygen-glucose deprivation or NMDA application. Rapid, reversible changes in dendritic structure may contribute to alterations in neuronal function following glutamate receptor stimulation under physiological or pathological conditions.
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U2 - 10.1006/nbdi.1996.0022
DO - 10.1006/nbdi.1996.0022
M3 - Article
C2 - 8980022
AN - SCOPUS:0030175149
SN - 0969-9961
VL - 3
SP - 215
EP - 227
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -