β-Amyloid-related peptides potentiate K+-evoked glutamate release from adult rat hippocampal slices

Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

“…135 Second, amyloid β can activate α 7 nicotinic receptors or NMDA receptors and increase Ca 2+ entry into the cell. This • Increase long-term depression 98,[108][109][110] • Decrease synaptic density and alter the morphology of dendritic spines 98,106,107,115 • Regulate glutamate uptake from the synapse 60,73,110,116,117 • Stimulate release of glutamate 117,118 • Increase endocytosis of AMPA and NMDA receptors 108,119 • Disrupt the postsynaptic density and prevent NMDA and AMPA receptors reaching the cell surface 120,121 • Increase tau phosphorylation/cell death [122][123][124][125][126] AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA = N-methyl-D-aspartate.…”

“…The effect is specific and appears to be mediated by direct interaction with the glutamatergic terminals. 118 This idea is reinforced by the evidence that preincubation of nerve endings with amyloid β1-42 can potentiate [ 14 C]glutamic acid release, at least in part, by interacting with an N-type voltageoperated calcium channel. 148 These findings, together with the observation that glutamatergic terminals containing VGLUT1 are localized in close apposition to the APP-positive neurons in the hippocampus, provide an anatomical basis to suggest a role of endogenously derived amyloid β peptides in the presynaptic regulation of glutamate release from selected brain regions.…”

“…At present, the underlying mech anisms by which amyloid β can potentiate glutamate release remains unclear, but it is of interest to note that nanomolar concentrations of amyloid β1-40 did not significantly alter glutamate release from the striatum, an area that is relatively spared in Alzheimer disease. 118 Whether micromolar concentrations of amyloid β peptide can enhance glutamate release from striatal slices remains to be established. However, these results raise the possibility that preferential vulnerability of hippocampal and cortical neurons could relate, at least in part, to their sensitivity to amyloid β peptides.…”

“…Antagonists of NMDA and AMPA receptors can prevent influx of Ca 2+ and cell death. 27 Alternatively, it is possible that amyloid β-related peptides can increase extracellular glutamate levels by potentiating release 117,118,155 and/or inhibiting the uptake of the neurotransmitter, 116,153 which can subsequently trigger death of neurons by excitotoxicity. It is therefore likely that a combination of reduced glutamate clearance from the synaptic cleft, increased release of glutamate from neurons and glia, and the subsequent activation of the glutamate receptors contribute to toxicity mediated by amyloid β-related peptides.…”

Dysfunctional synapse in Alzheimer's disease – A focus on NMDA receptors

“…Moreover, synthetic Aβ peptide species were also shown to potentiate K + -induced glutamate release from normal rodent hippocampus (Kabogo et al, 2010).…”