Banca de DEFESA: VITOR DA SILVEIRA ALVES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : VITOR DA SILVEIRA ALVES
DATE: 19/04/2023
TIME: 14:00
LOCAL: Campus São Bernardo do Campo
TITLE:

Cellular energy sources for the removal of cytoplasmic calcium in neurons.

PAGES: 65
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia de Órgãos e Sistemas
SPECIALTY: Neurofisiologia
SUMMARY:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the formation of β-amyloid (Aβ) peptide plaques and neurofibrillary tangles. Several studies point to the Aβ peptide as the primary cause of the disease, however, a long temporal gap is observed between the abnormal production of the peptide and the decline of cognitive functions common to AD. Changes in neuronal energy metabolism have been observed during the development of AD, where impairments in mechanisms and components for energy control are associated with several deleterious effects, among which, dysregulation in the dynamics of cytoplasmic Ca²⁺. Ca²⁺ is an important ion in neuronal signaling, and its intracellular concentration is carefully regulated. In neurons, after a transient increase in intracellular Ca²⁺, this ion is removed from this environment, mainly through Ca²⁺ pumps (Ca²⁺-ATPases) which use the energy stored in adenosine triphosphate (ATP) to pump Ca²⁺ out of the cell or into specific cellular compartments, such as the endoplasmic reticulum or mitochondria. The control of cytoplasmic Ca²⁺ is important because it plays a central role in many intracellular signaling processes and mechanisms, and its imbalance can lead to irreversible cell damage. Within this panorama, this work sought (i) to distinguish the main ATP-dependent mechanisms that contribute to the removal of intracellular Ca²⁺ in neurons and (ii) to establish which ATP-generating pathway, glycolytic or mitochondrial, would be linked to the main mechanisms of cytoplasmic Ca²⁺ clearance in hippocampal pyramidal neurons. Thus, Ca²⁺ transients were evoked, and their kinetic parameters quantified after punctual Ca²⁺-ATPase blockade in the plasma membrane (PMCA), endoplasmic reticulum (SERCA) and Na⁺-Ca²⁺ exchanger (NCX). In addition, blocking of glycolysis and mitochondria was also performed. Finally, the blockade of the main ATP-dependent mechanism for the removal of cytoplasmic Ca²⁺ was combined with the blockade of the mitochondrial or glycolytic pathway. The results show that PMCA is the main ATP-dependent mechanism for Ca²⁺ removal in the hippocampal pyramidal neuron and that this mechanism is maintained with ATP from glycolysis. We conclude, therefore, that the energy deficit that occurs in AD can directly impact intracellular Ca²⁺, causing changes in the dynamics and intracellular signaling of this ion.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1887027 - FERNANDO AUGUSTO DE OLIVEIRA RIBEIRO
Membro Titular - Examinador(a) Externo ao Programa - 1227329 - CESAR AUGUSTO JOAO RIBEIRO
Membro Titular - Examinador(a) Externo ao Programa - 1674592 - TIAGO RODRIGUES
Membro Titular - Examinador(a) Externo à Instituição - DAWIDSON ASSIS GOMES - UFMG
Membro Titular - Examinador(a) Externo à Instituição - MANOEL DE ARCISIO MIRANDA FILHO - UNIFESP
Membro Suplente - Examinador(a) Interno ao Programa - 1676367 - ALEXANDRE HIROAKI KIHARA
Membro Suplente - Examinador(a) Externo ao Programa - 1669152 - DANIEL CARNEIRO CARRETTIERO
Membro Suplente - Examinador(a) Externo à Instituição - APARECIDA EMIKO HIRATA - UNIFESP