Tauroursodeoxycholic acid suppresses amyloid β-induced synaptic toxicity in vitro and in APP/PS1 mice
| Autor: | Joana D. Amaral, Raquel B. Dias, Adrian C. Lo, Rita M. Ramalho, Ana Nunes, Rudi D'Hooge, Ana M. Sebastião, Cecília M. P. Rodrigues |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Aging
Dendritic spine Down-Regulation Mice Transgenic Biology Hippocampus Neuroprotection Presenilin Taurochenodeoxycholic Acid Synapse Amyloid beta-Protein Precursor Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Postsynaptic potential mental disorders Presenilin-1 Amyloid precursor protein Animals Rats Wistar 030304 developmental biology Cerebral Cortex Neurons 0303 health sciences Amyloid beta-Peptides Cell Death General Neuroscience Tauroursodeoxycholic acid Rats Cell biology Disease Models Animal Neuroprotective Agents nervous system chemistry Synapses Excitatory postsynaptic potential biology.protein Neurology (clinical) Geriatrics and Gerontology Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of Aging |
| ISSN: | 0197-4580 |
| Popis: | Synapses are considered the earliest site of Alzheimer's disease (AD) pathology, where synapse density is reduced, and synaptic loss is highly correlated with cognitive impairment. Tauroursodeoxycholic acid (TUDCA) has been shown to be neuroprotective in several models of AD, including neuronal exposure to amyloid β (Aβ) and amyloid precursor protein (APP)/presenilin 1 (PS1) double-transgenic mice. Here, we show that TUDCA modulates synaptic deficits induced by Aβ in vitro. Specifically, TUDCA reduced the downregulation of the postsynaptic marker postsynaptic density-95 (PSD-95) and the decrease in spontaneous miniature excitatory postsynaptic currents (mEPSCs) frequency, while increasing the number of dendritic spines. This contributed to the induction of more robust and synaptically efficient neurons, reflected in inhibition of neuronal death. In vivo, TUDCA treatment of APP/PS1 mice abrogated the decrease in PSD-95 reactivity in the hippocampus. Taken together, these results expand the neuroprotective role of TUDCA to a synaptic level, further supporting the use of this molecule as a potential therapeutic strategy for the prevention and treatment of AD. |
| Databáze: | OpenAIRE |
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