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Séminaire impromptu - Federico Bermudez-RattoniCortical dopamine activity reduction induced by beta amyloid is related with cognitive and synaptic plasticity deficits in Alzheimer’s disease.

Abstract :

 Alzheimer's disease (AD) is a neurodegenerative disease manifested by alterations in synaptic communication and memory loss.
However, the synaptic mechanisms underlying cognitive impairment are not entirely understood. Thus, we aimed to study the relationship between several neurotransmitters and cognitive dysfunction in AD models.

We used a transgenic mouse model of AD (3xTg-AD) and the administration of exogenous Amyloid-β oligomers into WT mice. We found that the accumulation of beta-amyloid decreases dopamine levels and impaired in vivo long-term potentiation (LTP) after high frequency electrical stimulation, which led to impaired recognition memory.

Surprisingly, increasing cortical dopamine levels rescued both HFS-induced LTP and memory.  Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models.

Selected publications

Moreno-Castilla P, Rodriguez-Duran LF, Guzman-Ramos K,
A, Escobar ML, Bermudez-Rattoni F (2016). Dopaminergic neurotransmission
dysfunction induced by amyloid-β transforms cortical long-term potentiation
into long-term depression and produces memory impairment.
<> Neurobiol of Aging,

Gómez-López S, Martínez-Silva AV, Montiel T, Osorio-Gómez D,
F, Massieu L, Escalante-Alcalde D (2016). Neural ablation of the PARK10
candidate Plpp3 leads to dopaminergic transmission deficits without
neurodegeneration. <> Scientific
Reports, 6:24028.

Guzmán-Ramos K, Moreno-Castilla P, Castro-Cruz M, McGaugh JL, Martínez-Coria
H, LaFerla FM, Bermúdez-Rattoni F (2012). Restoration of dopamine release
deficits during object recognition memory acquisition attenuates cognitive
impairment in a triple transgenic mice model of Alzheimer's disease.
<> Learning & Memory, 19(10):

Bermudez-Rattoni F (2010). Is memory consolidation a
multiple-circuit system?
<> Proc Natl Acad Sci U S A,

Guzmán-Ramos K, Osorio-Gómez D, Moreno-Castilla P, Bermúdez-Rattoni
F (2010).
Off-line concomitant release of dopamine and glutamate involvement in taste
memory consolidation. <> Journal
of Neurochemistry, 114(1):226-36.