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- W3202391384 abstract "Accumulation of amyloid beta oligomers (AβO) in Alzheimer's disease (AD) impairs hippocampal long-term potentiation (LTP), leading to memory deficits. Thus, identifying the molecular targets of AβO involved in LTP inhibition is critical for developing therapeutics for AD. Endocannabinoid (eCB) synthesis and release, a process collectively called eCB mobilization by hippocampal CA1 pyramidal cells, is known to facilitate LTP induction. eCB can be mobilized either by postsynaptic depolarization in an intracellular Ca2+ concentration ([Ca2+]i)-dependent pathway or by group 1 metabotropic glutamate receptor (mGluR) activation in a phospholipase Cβ (PLCβ)-dependent pathway. Moreover, group 1 mGluR activation during postsynaptic depolarization, which is likely to occur in vivo during memory processing, can cause synergistic enhancement of eCB (S-eCB) mobilization in a PLCβ-dependent pathway. Although AβO has been shown to disrupt [Ca2+]i-dependent eCB mobilization, the effect of AβO on PLCβ-dependent S-eCB mobilization and its association with LTP and hippocampus-dependent memory impairments in AD is unknown.We used in vitro whole-cell patch-clamp recordings and western blot analyses to investigate the effect of AβO on PLCβ protein levels, PLCβ-dependent S-eCB mobilization, and spike-timing-dependent potentiation (tLTP) in AβO-treated rat hippocampal slices in vitro. In addition, we assessed the relationship between PLCβ protein levels and hippocampus-dependent memory impairment by performing a contextual fear memory task in vivo in the 5XFAD mouse model of AD.We found that AβO treatment in rat hippocampal slices in vitro decreased hippocampal PLCβ1 protein levels and disrupted S-eCB mobilization, as measured by western blot analysis and in vitro whole-cell patch-clamp recordings. This consequently led to the impairment of NMDA receptor (NMDAR)-mediated tLTP at CA3-CA1 excitatory synapses in AβO-treated rat hippocampal slices in vitro. Application of the PLCβ activator, m-3M3FBS, in rat hippocampal slices reinstated PLCβ1 protein levels to fully restore S-eCB mobilization and NMDAR-mediated tLTP. In addition, direct hippocampal injection of m-3M3FBS in 5XFAD mice reinstated PLCβ1 protein levels to those observed in wild type control mice and fully restored hippocampus-dependent contextual fear memory in vivo in 5XFAD mice.We suggest that these results might be the consequence of memory impairment in AD by disrupting S-eCB mobilization. Therefore, we propose that PLCβ-dependent S-eCB mobilization could provide a new therapeutic strategy for treating memory deficits in AD." @default.
- W3202391384 created "2021-10-11" @default.
- W3202391384 creator A5003075910 @default.
- W3202391384 creator A5071444571 @default.
- W3202391384 date "2021-10-08" @default.
- W3202391384 modified "2023-09-27" @default.
- W3202391384 title "Activation of PLCβ1 enhances endocannabinoid mobilization to restore hippocampal spike-timing-dependent potentiation and contextual fear memory impaired by Alzheimer’s amyloidosis" @default.
- W3202391384 cites W1172796801 @default.
- W3202391384 cites W1545631641 @default.
- W3202391384 cites W1592286181 @default.
- W3202391384 cites W1602202713 @default.
- W3202391384 cites W1632580824 @default.
- W3202391384 cites W1654380405 @default.
- W3202391384 cites W1774176118 @default.
- W3202391384 cites W1834174605 @default.
- W3202391384 cites W1845377771 @default.
- W3202391384 cites W1933900320 @default.
- W3202391384 cites W1944651272 @default.
- W3202391384 cites W1950985564 @default.
- W3202391384 cites W1965612533 @default.
- W3202391384 cites W1966960464 @default.
- W3202391384 cites W1968083340 @default.
- W3202391384 cites W1969632782 @default.
- W3202391384 cites W1972183007 @default.
- W3202391384 cites W1972805775 @default.
- W3202391384 cites W1973401628 @default.
- W3202391384 cites W1973653064 @default.
- W3202391384 cites W1973703467 @default.
- W3202391384 cites W1990372425 @default.
- W3202391384 cites W1991905988 @default.
- W3202391384 cites W1998911334 @default.
- W3202391384 cites W2002734542 @default.
- W3202391384 cites W2003542304 @default.
- W3202391384 cites W2003655335 @default.
- W3202391384 cites W2004968757 @default.
- W3202391384 cites W2008331575 @default.
- W3202391384 cites W2010369438 @default.
- W3202391384 cites W2012422702 @default.
- W3202391384 cites W2012451528 @default.
- W3202391384 cites W2016912241 @default.
- W3202391384 cites W2018289835 @default.
- W3202391384 cites W2019372876 @default.
- W3202391384 cites W2023567526 @default.
- W3202391384 cites W2024517044 @default.
- W3202391384 cites W2028794471 @default.
- W3202391384 cites W2028985118 @default.
- W3202391384 cites W2029638208 @default.
- W3202391384 cites W2030085697 @default.
- W3202391384 cites W2035768389 @default.
- W3202391384 cites W2041018266 @default.
- W3202391384 cites W2041119066 @default.
- W3202391384 cites W2042651745 @default.
- W3202391384 cites W2048036339 @default.
- W3202391384 cites W2051741667 @default.
- W3202391384 cites W2054844651 @default.
- W3202391384 cites W2055568369 @default.
- W3202391384 cites W2059405665 @default.
- W3202391384 cites W2060674341 @default.
- W3202391384 cites W2061053265 @default.
- W3202391384 cites W2061342941 @default.
- W3202391384 cites W2072233684 @default.
- W3202391384 cites W2072625029 @default.
- W3202391384 cites W2079785767 @default.
- W3202391384 cites W2082151254 @default.
- W3202391384 cites W2082429191 @default.
- W3202391384 cites W2084015594 @default.
- W3202391384 cites W2086020154 @default.
- W3202391384 cites W2086721550 @default.
- W3202391384 cites W2086890404 @default.
- W3202391384 cites W2087519788 @default.
- W3202391384 cites W2096410114 @default.
- W3202391384 cites W2096473662 @default.
- W3202391384 cites W2099512174 @default.
- W3202391384 cites W2100610042 @default.
- W3202391384 cites W2100699923 @default.
- W3202391384 cites W2100837269 @default.
- W3202391384 cites W2106042714 @default.
- W3202391384 cites W2106537627 @default.
- W3202391384 cites W2109727228 @default.
- W3202391384 cites W2111445561 @default.
- W3202391384 cites W2111977586 @default.
- W3202391384 cites W2116240218 @default.
- W3202391384 cites W2116562654 @default.
- W3202391384 cites W2116754069 @default.
- W3202391384 cites W2120288177 @default.
- W3202391384 cites W2121091224 @default.
- W3202391384 cites W2128300673 @default.
- W3202391384 cites W2131832591 @default.
- W3202391384 cites W2134546663 @default.
- W3202391384 cites W2140653571 @default.
- W3202391384 cites W2144657811 @default.
- W3202391384 cites W2148389554 @default.
- W3202391384 cites W2148450564 @default.
- W3202391384 cites W2149601015 @default.
- W3202391384 cites W2151621161 @default.
- W3202391384 cites W2159031677 @default.
- W3202391384 cites W2162807572 @default.
- W3202391384 cites W2163982115 @default.
- W3202391384 cites W2165021720 @default.
- W3202391384 cites W2166267133 @default.