Andrea C. Paula-Lima, Chile

Universidad de Chile Department of Neuroscience

Pharmacist and PhD in Biological Chemistry from the Federal University of Rio de Janeiro, Andrea Paula-Lima developed her post-doctorate at the University of Chile, where she is currently Associate Professor of the Faculty of Dentistry and Faculty of Medicine. For her professional contribution to the study of Alzheimer's disease (AD), she won the Junior Faculty Award from the AAT-ADPD 2011 (Barcelona, Spain) and in 2013 (Florence, Italy) and received distinctions from important scientific societies such as the Society for Neurosciences (USA), the National Academy of Sciences of Chile and Brazil, the Council for the Lindau Nobel Laureate Meetings, Foundation Lindau Nobel Laureate Meetings and the the Royal Society. Using experimental models ranging from the in vitro to the study in patients, she is interested in elucidating and blocking the intraneuronal signaling pathways activated by beta-amyloid peptide oligomers, with emphasis on those pathways that are dependent on calcium ion as the second messenger. She is also searching for functional alterations detectable by EEG in patients, to contribute to the early diagnosis of AD.

Presenter of 2 Presentations

Conference Calendar

AMYLOID-Β OLIGOMERS CONTRIBUTE TO THE CALCIUM DYSFUNCTION IN ALZHEIMER´S DISEASE BY INTERRUPTING NEUROPROTECTIVE GENE EXPRESSION INDUCED BY NEURONAL ACTIVITY

Session Name

SYNAPTIC DAMAGE AND NEURONAL PLASTICITY

Session Type

SYMPOSIUM

Date

11.03.2021, Thursday

Session Time

10:00 - 12:00

Room

On Demand Symposia D

Lecture Time

10:30 - 10:45

Presenter

Andrea C. Paula-Lima, Chile

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Abstract

Abstract

Aims

Amyloid-beta oligomers (AβOs) are synaptotoxins that induce aberrant Ca²⁺-signals and promote ROS generation, leading to synaptic plasticity disruption. We have reported that AβOs induce a sustained but low-intensity cytoplasmic [Ca²⁺]i increase in neurons, which arises from NMDA receptor-mediated Ca²⁺ entry and subsequent amplification via Ca²⁺-induced Ca²⁺-release, mediated by ryanodine receptor (RyR) channels. We also reported that RyR2 isoform has a key role in the mitochondrial dysfunctions induced by AβOs-treatment in neurons, and in the memory-defects observed in rats injected with AβOs. Since gene expression changes are mediated by the rapid activation and expression of transcription factors, we evaluated the expression of RyR2 and distinct activity-dependent genes regulating the expression of neurotrophic factors and antioxidant enzymes in response to AβOs. We also tested the combined effects of AβOs and Gabazine (GBZ), a GABA(A)-receptor blocker that functions as an inductor of synaptic activity.

Methods

Primary hippocampal cultures were pre-incubated for 6 h with AβOs before the Gabazine (GBZ) stimulation for 2h. RyR2, Npas4, BDNF, Glutamate-Cysteine-Ligase (GCL) and NADPH-Quinone-Oxidoreductase (Nqo1) mRNA expression levels were determined by RT-qPCR.

Results

GBZ alone induced in just 2 h an increase in RyR2 expression, BDNF, Npas4, glutamate-Cysteine-Ligase (GCL), and NADPH-Quinone-Oxidoreductase (Nqo1). Conversely, pre-treatment with AβOs prevented these increases in the mRNA expression levels of these proteins induced by GBZ.

Conclusions

We propose that AβOs block the activation of signaling pathways induced by stimulation of neuronal activity by GBZ, leading to a disruption of the neuroprotective gene expression pathways essential to memory and learning processes, which are affected in neurodegenerative diseases.

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