TY - JOUR
T1 - Presynaptic defects underlying impaired learning and memory function in lipoprotein Lipase-deficient mice
AU - Xian, Xunde
AU - Liu, Tingting
AU - Yu, Jia
AU - Wang, Yuhui
AU - Miao, Yifei
AU - Zhang, Jianjun
AU - Yu, Yan
AU - Ross, Colin
AU - Karasinska, Joanna M.
AU - Hayden, Michael R.
AU - Liu, George
AU - Chui, Dehua
PY - 2009/4/8
Y1 - 2009/4/8
N2 - Lipoprotein lipase (LPL) is predominantly expressed in adipose and muscle where it plays a crucial role in the metabolism of triglyceriderich plasma lipoproteins. LPL is also expressed in the brain with highest levels found in the pyramidal cells of the hippocampus, suggesting a possible role for LPL in the regulation of cognitive function. However, very little is currently known about the specific role of LPL in the brain. We have generated a mouse model of LPL deficiency which was rescued from neonatal lethality by somatic gene transfer. These mice show no exogenous and endogenous LPL expression in the brain. To study the role of LPL in learning and memory, the performance of LPL-deficient mice was tested in two cognitive tests. In a water maze test, LPL-deficient mice exhibited increased latency to escape platform and increased mistake frequency. Decreased latency to platform in the step-down inhibitory avoidance test was observed, consistent with impaired learning and memory in these mice. Transmission electron microscopy revealed a significant decrease in the number of presynaptic vesicles in the hippocampus of LPL-deficient mice. The levels of the presynaptic marker synaptophysin were also reduced in the hippocampus, whereas postsynaptic marker postsynaptic density protein 95 levels remained unchanged in LPL-deficient mice. Theses findings indicate that LPL plays an important role in learning and memory function possibly by influencing presynaptic function.
AB - Lipoprotein lipase (LPL) is predominantly expressed in adipose and muscle where it plays a crucial role in the metabolism of triglyceriderich plasma lipoproteins. LPL is also expressed in the brain with highest levels found in the pyramidal cells of the hippocampus, suggesting a possible role for LPL in the regulation of cognitive function. However, very little is currently known about the specific role of LPL in the brain. We have generated a mouse model of LPL deficiency which was rescued from neonatal lethality by somatic gene transfer. These mice show no exogenous and endogenous LPL expression in the brain. To study the role of LPL in learning and memory, the performance of LPL-deficient mice was tested in two cognitive tests. In a water maze test, LPL-deficient mice exhibited increased latency to escape platform and increased mistake frequency. Decreased latency to platform in the step-down inhibitory avoidance test was observed, consistent with impaired learning and memory in these mice. Transmission electron microscopy revealed a significant decrease in the number of presynaptic vesicles in the hippocampus of LPL-deficient mice. The levels of the presynaptic marker synaptophysin were also reduced in the hippocampus, whereas postsynaptic marker postsynaptic density protein 95 levels remained unchanged in LPL-deficient mice. Theses findings indicate that LPL plays an important role in learning and memory function possibly by influencing presynaptic function.
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U2 - 10.1523/JNEUROSCI.0297-09.2009
DO - 10.1523/JNEUROSCI.0297-09.2009
M3 - Article
C2 - 19357293
AN - SCOPUS:65549113066
SN - 0270-6474
VL - 29
SP - 4681
EP - 4685
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 14
ER -