Delayed reduction in hippocampal postsynaptic density protein-95 expression temporally correlates with cognitive dysfunction following controlled cortical impact in mice
被引:79
|
作者:
Wakade, Chandramohan
论文数: 0引用数: 0
h-index: 0
机构:
Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USAMed Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
Wakade, Chandramohan
[1
]
Sukumari-Ramesh, Sangeetha
论文数: 0引用数: 0
h-index: 0
机构:
Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USAMed Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
Sukumari-Ramesh, Sangeetha
[1
]
Laird, Melissa D.
论文数: 0引用数: 0
h-index: 0
机构:
Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USAMed Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
Laird, Melissa D.
[1
]
Dhandapani, Krishnan M.
论文数: 0引用数: 0
h-index: 0
机构:
Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USAMed Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
Dhandapani, Krishnan M.
[1
]
Vender, John R.
论文数: 0引用数: 0
h-index: 0
机构:
Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USAMed Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
Vender, John R.
[1
]
机构:
[1] Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
Object. Traumatic brain injury (TBI) induces significant neurological damage, including deficits in learning and memory, which contribute to a poor clinical prognosis. Treatment options to limit cognitive decline and promote neurological recovery are lacking, in part due to a poor understanding of the secondary or delayed processes that contribute to brain injury. In the present study, the authors characterized the temporal and spatial changes in the expression of postsynaptic density protein-95 (PSD-95), a key scaffolding protein implicated in excitatory synaptic signaling, after controlled cortical impacts in mice. Neurological injury, as assessed by the open-field activity test and the novel object recognition test, was compared with changes in PSD-95 expression. Methods. Adult male CD-1 mice were subjected to controlled cortical impacts to simulate moderate TBI in humans. The spatial and temporal expression of PSD-95 was analyzed in the cerebral cortex and hippocampus at various time points following injury and sham operations. Neurological assessments were performed to compare changes in PSD-95 with cognitive deficits. Results. A significant decrease in PSD-95 expression was observed in the ipsilateral hippocampus beginning on Day 7 postinjury. The loss of PSD-95 corresponded with a concomitant reduction in immunoreactivity for NeuN (neuronal nuclei), a neuron-specific marker. Aside from the contused cortex, a significant loss of PSD-95 immunore-activity was not observed in the cerebral cortex. The delayed loss of hippocampal PSD-95 directly correlated with the onset of behavioral deficits, suggesting a possible causative role for PSD-95 in behavioral abnormalities following head trauma. Conclusions. A delayed loss of hippocampal synapses was observed following head trauma in mice. These data may suggest a cellular mechanism to explain the delayed learning and memory deficits in humans after TBI and provide a potential framework for further testing to implicate PSD-95 as a clinically relevant therapeutic target. (DOI: 10.3171/2010.3.JNS091212)
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Xu, Sherry L.
Zhu, Kevin Y.
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Zhu, Kevin Y.
Bi, Cathy W. C.
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Bi, Cathy W. C.
Choi, Roy C. Y.
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Choi, Roy C. Y.
Miernisha, Abudureyimu
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Miernisha, Abudureyimu
Yan, Artemis L.
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Yan, Artemis L.
Maiwulanjiang, Maitinuer
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Maiwulanjiang, Maitinuer
Men, Simon W. X.
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Men, Simon W. X.
Dong, Tina T. X.
论文数: 0引用数: 0
h-index: 0
机构:Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
Dong, Tina T. X.
Tsim, Karl W. K.
论文数: 0引用数: 0
h-index: 0
机构:
Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R ChinaHong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China
机构:
Carnegie Mellon Univ, Biomed Engn, Pittsburgh, PA 15213 USAAllegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Sun, Zhuopin
Liu, Shiying
论文数: 0引用数: 0
h-index: 0
机构:
Carnegie Mellon Univ, Biomed Engn, Pittsburgh, PA 15213 USAAllegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Liu, Shiying
Kharlamov, Elena A.
论文数: 0引用数: 0
h-index: 0
机构:
Allegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Allegheny Gen Hosp, Allegheny Hlth Network Res Inst, Pittsburgh, PA 15212 USA
Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USAAllegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Kharlamov, Elena A.
Miller, Eric R.
论文数: 0引用数: 0
h-index: 0
机构:
Allegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Allegheny Gen Hosp, Allegheny Hlth Network Res Inst, Pittsburgh, PA 15212 USA
Carnegie Mellon Univ, Biomed Engn, Pittsburgh, PA 15213 USAAllegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Miller, Eric R.
Kelly, Kevin M.
论文数: 0引用数: 0
h-index: 0
机构:
Allegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
Allegheny Gen Hosp, Allegheny Hlth Network Res Inst, Pittsburgh, PA 15212 USA
Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA
Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USAAllegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA
机构:
Washington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
George Washington Univ, Dept Biochem & Mol Med, Sch Med, Washington, DC 20052 USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
Zhou, June
Burns, Mark P.
论文数: 0引用数: 0
h-index: 0
机构:
Georgetown Univ, Sch Med, Dept Neurosci, Washington, DC USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
Burns, Mark P.
Huynh, Linda
论文数: 0引用数: 0
h-index: 0
机构:
Washington DC VA Med Ctr, Res Serv, Washington, DC 20422 USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
Huynh, Linda
Villapol, Sonia
论文数: 0引用数: 0
h-index: 0
机构:
Georgetown Univ, Sch Med, Dept Neurosci, Washington, DC USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
Villapol, Sonia
Taub, Daniel D.
论文数: 0引用数: 0
h-index: 0
机构:
Washington DC VA Med Ctr, Translat Med Sect, Washington, DC USA
Georgetown Univ, Dept Biochem & Mol & Cell Biol, Sch Med, Washington, DC USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
Taub, Daniel D.
Saavedra, Juan M.
论文数: 0引用数: 0
h-index: 0
机构:
Georgetown Univ, Dept Physiol & Pharmacol, Sch Med, Washington, DC USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
Saavedra, Juan M.
Blackman, Marc R.
论文数: 0引用数: 0
h-index: 0
机构:
Washington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA
George Washington Univ, Dept Biochem & Mol Med, Sch Med, Washington, DC 20052 USA
George Washington Univ, Dept Med, Sch Med, Washington, DC USA
Georgetown Univ, Dept Med, Sch Med, Washington, DC USAWashington DC VA Med Ctr, Res Serv, Washington, DC 20422 USA