Enhanced expression of Pctk1, Tcf12 and Ccnd1 in hippocampus of rats: Impact on cognitive function, synaptic plasticity and pathology.
Enhanced expression of Pctk1, Tcf12 and Ccnd1 in hippocampus of rats: Impact on cognitive function, synaptic plasticity and pathology.
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DOI：
10.1016/j.nlm.2011.09.006
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发表时间：
2012-01
影响因子：
2.7
通讯作者：
Kumar, Ashok
中科院分区：
文献类型：
--
作者：
Wu, Ke;Li, Shoudong;Bodhinathan, Karthik;Meyers, Craig;Chen, Weijun;Campbell-Thompson, Martha;McIntyre, Lauren;Foster, Thomas C.;Muzyczka, Nicholas;Kumar, Ashok
We previously identified a set of 50 genes that were differentially transcribed in the hippocampal CA1 region of aged, learning-impaired rats compared to aged, superior learning animals during a Morris water maze paradigm. In the current study we expressed three of these genes (Pctk1, Tcf12 and Ccnd1), which had shown increased transcription in aged, learning impaired rats, in the hippocampus of young rats using viral gene transfer and tested for learning and memory deficits at age 7–14 months. Pctk1 injected animals displayed a modest deficit in acquiring latency in both the Morris Water Maze and the reverse Morris maze. In the radial arm water maze paradigm, Pctk1, Tcf12 and Ccnd1 expressing animals all showed significant deficits in spatial working memory compared to controls. Rats injected with Ccnd1 and Tcf12, but not Pctk1, also showed a significant deficit in spatial reference memory in the radial arm water maze. Electrophysiological experiments revealed no difference in LTP in Ccnd1 and Pctk1 animals. However, LTD induced by low frequency stimulation was observed in control and Ccnd1 animals, but not in Pctk1 treated animals. In addition, neither Ccnd1 nor Pctk1 expression produced any detectable neuropathology. In contrast Tcf12 expressing animals displayed significant neurodegeneration in both CA1 and dentate gyrus. Several Tcf12 animals also developed tumors that appeared to be glioblastomas, suggesting that aberrant Tcf12 expression in the hippocampus is tumorigenic. Thus, behavioral experiments suggested that overexpression of Pctk1 and Ccnd1 produce a deficit in learning and memory, but electrophysiological experiments do not point to a simple mechanism. In contrast, the learning and memory deficits in Tcf12 animals are likely due to neuropathology associated with Tcf12 gene expression.
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DOI：
10.1073/pnas.0711053105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Gorbatyuk, Oleg S.;Li, Shoudong;Muzyczka, Nicholas
通讯作者：
Muzyczka, Nicholas
影响因子：
12.4
作者：
Gorbatyuk, Oleg S.;Li, Shoudong;Muzyczka, Nicholas
通讯作者：
Muzyczka, Nicholas
影响因子：
3.4
作者：
Acevedo, Summer F.;Tittle, Sierra;Raber, Jacob
通讯作者：
Raber, Jacob
DOI：
10.1523/jneurosci.5485-09.2010
发表时间：
2010-02-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bodhinathan K;Kumar A;Foster TC
通讯作者：
Foster TC
影响因子：
4.3
作者：
Kozar, K;Sicinski, P
通讯作者：
Sicinski, P