Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Ab and tau pathology in transgenic mouse models of Alzheimer’s disease
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Charles Y. Shao Suzanne S. Mirra Hameetha B. R. Sait Todd C. Sacktor Einar M. Sigurdsson
- چاپ و سال / کشور: 2011
Description
Impairment of synaptic plasticity underlies memory dysfunction inAlzheimer’s disease (AD). Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Ab deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendritesmarkedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumulated in Hirano bodies in hippocampal neurons. Our findings support the notion that eitherAb or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. Furthermore, this PSD- 95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits.
Acta Neuropathol DOI 10.1007/s00401-011-0843-x Received: 28 January 2011 / Revised: 22 April 2011 / Accepted: 21 May 2011
