Glutamatergic synaptic depression by synthetic amyloid β‐peptide in the medial septum

Santos-Torres, Julio; Fuente, Antonio de la; Criado, Julio J.; Riolobos, Adelaida Sánchez; Heredia, Margarita; Yajeya, Javier

doi:10.1002/jnr.21150

Cited by 20 publications

(32 citation statements)

References 61 publications

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“…Deficit in glutamatergic synaptic transmission and synchronous network activity have been found in hippocampal slices from transgenic mice over expressing the human form of the amyloid precursor protein (APP) harboring the Swedish mutation (Brown et al, 2005), suggesting that Aβ increases may lead to dysfunctional glutamatergic systems. In the medial septum bath application of Aβ (1-40 and 25-35) also depressed glutamatergic synaptic transmission (Santos-Torres et al, 2007).…”

Section: Discussionmentioning

confidence: 91%

Medial septal β-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Colom¹,

Castañeda²,

Bañuelos³

et al. 2010

Neurobiology of Aging

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Degeneration of septal neurons in Alzheimer's disease (AD) results in abnormal information processing at cortical circuits and consequent brain dysfunction. The septum modulates the activity of hippocampal and cortical circuits and is crucial to the initiation and occurrence of oscillatory activities such as the hippocampal theta rhythm. Previous studies suggest that amyloid β peptide (Aβ) accumulation may trigger degeneration in AD. This study evaluates the effects of single injections of Aβ 1-40 into the medial septum. Immunohistochemistry revealed a decrease in septal cholinergic (57%) and glutamatergic (53%) neurons in Aβ 1-40 treated tissue. Additionally, glutamatergic terminals were significantly less in Aβ treated tissue. In contrast, septal GABAergic neurons were spared. Unitary recordings from septal neurons and hippocampal field potentials revealed an approximately 50% increase in firing rates of slow firing septal neurons during theta rhythm and large irregular amplitude (LIA) hippocampal activities and a significantly reduced hippocampal theta rhythm power (49%) in Aβ 1-40 treated tissue. Aβ also markedly reduced the proportion of slow firing septal neurons correlated to the hippocampal theta rhythm by 96%. These results confirm that Aβ alters the anatomy and physiology of the medial septum contributing to septohippocampal dysfunction. The Aβ induced injury of septal cholinergic and glutamatergic networks may contribute to an altered hippocampal theta rhythm which may underlie the memory loss typically observed in AD patients.

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Section: Discussionmentioning

confidence: 91%

Medial septal β-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Colom¹,

Castañeda²,

Bañuelos³

et al. 2010

Neurobiology of Aging

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“…In separate studies, depression of synaptic transmission by Aβ or Aβ fragments (eg. Aβ [25][26][27][28][29][30][31][32][33][34][35] ) has been linked to inhibition of voltagegated Ca 2+ channels (Ashenafi et al, 2005;Santos-Torres et al, 2007) and reduction of AMPA receptor currents (Hsieh et al, 2006;Shemer et al, 2006;Ting et al, 2007). Furthermore, as soluble Aβ levels rise in AD, stimulation of DA release might also lead to synaptic depression by depletion over the long run, dependent on the cholinergic activity at the presynaptic nAChRs as well as nerve activity Kamenetz et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Dopamine release in prefrontal cortex in response to β-amyloid activation of α7∗ nicotinic receptors

Khan

Nichols

2007

Brain Research

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The levels of soluble beta amyloid (Aβ) are correlated with symptom severity in Alzheimer's disease. Soluble Aβ has been shown to disrupt synaptic function and it has been proposed that accumulation of soluble Aβ triggers synapse loss over the course of the disease. Numerous studies indicate that soluble Aβ has multiple targets, one of which appears to be the nicotinic acetylcholine receptor, particularly for Aβ concentrations of pM-nM. Moreover, pM-nM soluble Aβ was found to increase presynaptic Ca 2+ levels, suggesting that it may have an impact on neurotransmitter release. In the present study, soluble Aβ was perfused into mouse prefrontal cortex and the effect on the release of dopamine outflow via microdialysis was assessed. In the presence of tetrodotoxin, Aβ 1-42 at 100nM evoked the release of dopamine to ∼170% of basal levels. The Aβ 1-42 -evoked dopamine release was sensitive to antagonists of α7 nicotinic receptors and was absent in mice harboring a null mutation for the α7 nicotinic subunit, but was intact in mice harboring a null mutation for the β2 nicotinic subunit. The control peptide Aβ 40-1 was without effect. In contrast, Aβ 1-42 at 1-10pM caused a profound but slowly developing decrease in dopamine outflow. These results suggest that Aβ alters dopamine release in mouse prefrontal cortex, perhaps involving distinct targets as it accumulates during Alzheimer's disease and leading to disruption of synaptic signaling.

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“…Thus, perfusion of MS slices with Ab40 reduced EPSPs and this effect was blocked by calcicludine (a selective L-type Ca 2? channel antagonist) and also by pirenzepine, a relatively selective M1-receptor antagonist (Santos-Torres et al 2007).…”

Section: Role Of Machrsmentioning

confidence: 99%

Alzheimer’s Disease Amyloid β-Protein and Synaptic Function

et al. 2009

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Alzheimer's disease (AD) is characterized neuropathologically by the deposition of different forms of amyloid beta-protein (A beta) including variable amounts of soluble species that correlate with severity of dementia. The extent of synaptic loss in the brain provides the best morphological correlate of cognitive impairment in clinical AD. Animal research on the pathophysiology of AD has therefore focussed on how soluble A beta disrupts synaptic mechanisms in vulnerable brain regions such as the hippocampus. Synaptic plasticity in the form of persistent activity-dependent increases or decreases in synaptic strength provide a neurophysiological substrate for hippocampal-dependent learning and memory. Acute treatment with human-derived or chemically prepared soluble A beta that contains certain oligomeric assemblies, potently and selectively disrupts synaptic plasticity causing inhibition of long-term potentiation (LTP) and enhancement of long-term depression (LTD) of glutamatergic transmission. Over time these and related actions of A beta have been implicated in reducing synaptic integrity. This review addresses the involvement of neurotransmitter intercellular signaling in mediating or modulating the synaptic plasticity disrupting actions of soluble A beta, with particular emphasis on the different roles of glutamatergic and cholinergic mechanisms. There is growing evidence to support the view that NMDA and possibly nicotinic receptors are critically involved in mediating the disruptive effect of A beta and that targeting muscarinic receptors can indirectly modulate A beta's actions. Such studies should help inform ongoing and future clinical trials of drugs acting through the glutamatergic and cholinergic systems.

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Glutamatergic synaptic depression by synthetic amyloid β‐peptide in the medial septum

Cited by 20 publications

References 61 publications

Medial septal β-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Medial septal β-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Dopamine release in prefrontal cortex in response to β-amyloid activation of α7∗ nicotinic receptors

Alzheimer’s Disease Amyloid β-Protein and Synaptic Function

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