| Autor: |
Winston CN; 1 Department of Neuroscience, Laboratory for Brain Injury and Dementia, Georgetown University Medical Center , Washington, DC., Chellappa D, Wilkins T, Barton DJ, Washington PM, Loane DJ, Zapple DN, Burns MP |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neurotrauma [J Neurotrauma] 2013 Dec 01; Vol. 30 (23), pp. 1966-72. Date of Electronic Publication: 2013 Oct 12. |
| DOI: |
10.1089/neu.2013.2960 |
| Abstrakt: |
The clinical manifestations that occur after traumatic brain injury (TBI) include a wide range of cognitive, emotional, and behavioral deficits. The loss of excitatory synapses could potentially explain why such diverse symptoms occur after TBI, and a recent preclinical study has demonstrated a loss of dendritic spines, the postsynaptic site of the excitatory synapse, after fluid percussion injury. The objective of this study was to determine if controlled cortical impact (CCI) also resulted in dendritic spine retraction and to probe the underlying mechanisms of this spine loss. We used a unilateral CCI and visualized neurons and dendtritic spines at 24 h post-injury using Golgi stain. We found that TBI caused a 32% reduction of dendritic spines in layer II/III of the ipsilateral cortex and a 20% reduction in the dendritic spines of the ipsilateral dentate gyrus. Spine loss was not restricted to the ipsilateral hemisphere, however, with similar reductions in spine numbers recorded in the contralateral cortex (25% reduction) and hippocampus (23% reduction). Amyloid-β (Aβ), a neurotoxic peptide commonly associated with Alzheimer disease, accumulates rapidly after TBI and is also known to cause synaptic loss. To determine if Aβ contributes to spine loss after brain injury, we administered a γ-secretase inhibitor LY450139 after TBI. We found that while LY450139 administration could attenuate the TBI-induced increase in Aβ, it had no effect on dendritic spine loss after TBI. We conclude that the acute, global loss of dendritic spines after TBI is independent of γ-secretase activity or TBI-induced Aβ accumulation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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