The amyloid precursor protein (APP) is critical in the pathogenesis of Alzheimer's disease. The question of its normal biological function in neurons, in which it is predominantly located at synapses, is still unclear. Using autaptic cultures of hippocampal neurons, we demonstrate that hippocampal neurons lacking APP show significantly enhanced amplitudes of evoked AMPA- and NMDA-receptor-mediated EPSCs. The size of the readily releasable synaptic vesicle pool was also increased in neurons lacking APP, whereas the release probability was not affected. In addition, the analysis of spontaneous miniature synaptic currents revealed an augmented frequency in neurons lacking APP, whereas the amplitude of miniature synaptic currents was not found to be altered. Together, these findings strongly indicate that lack of APP increases the number of functional synapses. This hypothesis is further supported by morphometric immunohistochemical analysis revealing an increase of synaptophysin-positive puncta per cultured APP knock-out neuron. In conclusion, lack of APP affects synapse formation and transmission in cultured hippocampal neurons.
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Chang, EH
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Savage, MJ
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Savage, MJ
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Flood, DG
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Flood, DG
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Thomas, JM
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Thomas, JM
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Levy, RB
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Levy, RB
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Mahadomrongkul, V
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Mahadomrongkul, V
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Shirao, T
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Aoki, C
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Aoki, C
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Huerta, PT
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Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USACornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
机构:
Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mental Retardat Res Ctr, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Chang, EH
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Savage, MJ
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h-index: 0
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Savage, MJ
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Flood, DG
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h-index: 0
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Flood, DG
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Thomas, JM
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机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Thomas, JM
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Levy, RB
论文数: 0引用数: 0
h-index: 0
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Levy, RB
;
Mahadomrongkul, V
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h-index: 0
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Mahadomrongkul, V
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机构:
Shirao, T
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Aoki, C
论文数: 0引用数: 0
h-index: 0
机构:Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
Aoki, C
;
Huerta, PT
论文数: 0引用数: 0
h-index: 0
机构:
Cornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USACornell Univ, Weill Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
机构:
Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mental Retardat Res Ctr, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA