Amyloid Beta Oligomers-Induced Ca Entry Pathways: Role of Neuronal Networks, NMDA Receptors and Amyloid Channel Formation.

The molecular basis of amyloid toxicity in Alzheimer's disease (AD) remains controversial. Amyloid β (Aβ) oligomers promote Ca influx, mitochondrial Ca overload and apoptosis in hippocampal neurons in vivo and in vitro, but the primary Ca entry pathways are unclear. We studied Ca entry pathways induced by Aβ oligomers in rat hippocampal and cerebellar neurons.

Neurotoxic Ca Signaling Induced by Amyloid-β Oligomers in Aged Hippocampal Neurons In Vitro.

Alzheimer's disease (AD), the most prevalent dementia linked to aging, involves neurotoxic effects of amyloid β species and dishomeostasis of intracellular Ca. To investigate mechanisms of AD, the effects of soluble species of amyloid β oligomers (Aβo) prepared in medium devoid of glutamate receptor agonists can be tested on intracellular Ca in long-term cultures of rat hippocampal neurons that reflect aging neurons. Furthermore, changes in expression of proteins involved in oligomer responses and AD can be tested in the same neurons using quantitative immunofluorescence.

Is it All Said for NSAIDs in Alzheimer's Disease? Role of Mitochondrial Calcium Uptake.

Objectives: Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing.

A new procedure for amyloid β oligomers preparation enables the unambiguous testing of their effects on cytosolic and mitochondrial Ca(2+) entry and cell death in primary neurons.

Oligomers of the amyloid β peptide (Aβo) are becoming the most likely neurotoxin in Alzheimer's disease. Controversy remains on the mechanisms involved in neurotoxicity induced by Aβo and the targets involved. We have reported that Aβo promote Ca(2+) entry, mitochondrial Ca(2+) overload and apoptosis in cultured cerebellar neurons.

Susceptibility to excitotoxicity in aged hippocampal cultures and neuroprotection by non-steroidal anti-inflammatory drugs: role of mitochondrial calcium.

Brain damage after insult and cognitive decline are related to excitotoxicity and strongly influenced by aging, yet mechanisms of aging-dependent susceptibility to excitotoxicity are poorly known. Several non-steroidal anti-inflammatory drugs (NSAIDs) may prevent excitotoxicity and cognitive decline in the elderly by an unknown mechanism. Interestingly, after several weeks in vitro, hippocampal neurons display important hallmarks of neuronal aging in vivo.

Regulation of mitochondrial permeability transition pore by PINK1.

Background: Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) have been linked to familial Parkinson's disease, but the underlying pathogenic mechanism remains unclear. We previously reported that loss of PINK1 impairs mitochondrial respiratory activity in mouse brains.

Results: In this study, we investigate how loss of PINK1 impairs mitochondrial respiration using cultured primary fibroblasts and neurons.

Study of neurotoxic intracellular calcium signalling triggered by amyloids.

Neurotoxicity in Alzheimer's disease (AD) is associated to dishomeostasis of intracellular Ca(2+) induced by amyloid β peptide (Aβ) species. Understanding of the effects of Aβ on intracellular Ca(2+) homeostasis requires preparation of the different Aβ assemblies including oligomers and fibrils and the testing of their effects on cytosolic and mitochondrial Ca(2+) in neurons. Procedures for cerebellar granule cell culture, preparation of Aβ species as well as fluorescence and bioluminescence imaging of cytosolic and mitochondrial Ca(2+) in neurons are described.