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 [1 ]
Sukumari-Ramesh, Sangeetha [1 ]
Laird, Melissa D. [1 ]
Dhandapani, Krishnan M. [1 ]
Vender, John R. [1 ]
机构
[1] Med Coll Georgia, Dept Neurosurg, Augusta, GA 30912 USA
基金
美国国家卫生研究院;
关键词
traumatic brain injury; glutamate; synaptic plasticity; hippocampus; TRAUMATIC BRAIN-INJURY; HEAD-INJURY; MEMORY; ACTIVATION; HEMORRHAGE; CONTUSION; PATHOLOGY; MODERATE; NEURONS; ADULTS;
D O I
10.3171/2010.3.JNS091212
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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)
引用
收藏
页码:1195 / 1201
页数:7
相关论文
共 3 条
  • [1] Flavonoids Induce the Expression of Synaptic Proteins, Synaptotagmin, and Postsynaptic Density Protein-95 in Cultured Rat Cortical Neuron
    Xu, Sherry L.
    Zhu, Kevin Y.
    Bi, Cathy W. C.
    Choi, Roy C. Y.
    Miernisha, Abudureyimu
    Yan, Artemis L.
    Maiwulanjiang, Maitinuer
    Men, Simon W. X.
    Dong, Tina T. X.
    Tsim, Karl W. K.
    PLANTA MEDICA, 2013, 79 (18) : 1710 - 1714
  • [2] Hippocampal neuropeptide Y protein expression following controlled cortical impact and posttraumatic epilepsy
    Sun, Zhuopin
    Liu, Shiying
    Kharlamov, Elena A.
    Miller, Eric R.
    Kelly, Kevin M.
    EPILEPSY & BEHAVIOR, 2018, 87 : 188 - 194
  • [3] Temporal changes in cortical and hippocampal expression of genes important for Brain glucose Metabolism Following controlled cortical impact injury in Mice
    Zhou, June
    Burns, Mark P.
    Huynh, Linda
    Villapol, Sonia
    Taub, Daniel D.
    Saavedra, Juan M.
    Blackman, Marc R.
    FRONTIERS IN ENDOCRINOLOGY, 2017, 8