A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer’s brain DOI Open Access
Shaomin Li, Dennis J. Selkoe

Journal of Neurochemistry, Journal Year: 2020, Volume and Issue: 154(6), P. 583 - 597

Published: March 17, 2020

It is increasingly accepted that early cognitive impairment in Alzheimer's disease results considerable part from synaptic dysfunction caused by the accumulation of a range oligomeric assemblies amyloid β-protein (Aβ). Most studies have used synthetic Aβ peptides to explore mechanisms memory deficits rodent models, but recent work suggests isolated human (AD) brain tissue are far more potent and disease-relevant. Although reductionist experiments show oligomers impair plasticity neuronal viability, responsible only partly understood. Glutamatergic receptors, GABAergic nicotinic insulin cellular prion protein, inflammatory mediators, diverse signaling pathways all been suggested. Studies using AD brain-derived soluble suggest certain bioactive forms (principally small, diffusible oligomers) can disrupt plasticity, including binding plasma membranes changing excitatory-inhibitory balance, perturbing mGluR, PrP, other surface proteins, down-regulating glutamate transporters, causing spillover, activating extrasynaptic GluN2B-containing NMDA receptors. We synthesize these emerging data into mechanistic hypothesis for failure be modified as new knowledge added specific therapeutics developed.

Language: Английский

About Sleep's Role in Memory DOI
Björn Rasch, Jan Born

Physiological Reviews, Journal Year: 2013, Volume and Issue: 93(2), P. 681 - 766

Published: April 1, 2013

Over more than a century of research has established the fact that sleep benefits retention memory. In this review we aim to comprehensively cover field “sleep and memory” by providing historical perspective on concepts discussion recent key findings. Whereas initial theories posed passive role for enhancing memories protecting them from interfering stimuli, current highlight an active in which undergo process system consolidation during sleep. older concentrated rapid-eye-movement (REM) sleep, work revealed importance slow-wave (SWS) memory also enlightened some underlying electrophysiological, neurochemical, genetic mechanisms, as well developmental aspects these processes. Specifically, newer findings characterize brain state optimizing consolidation, opposition waking being optimized encoding memories. Consolidation originates reactivation recently encoded neuronal representations, occur SWS transform respective representations integration into long-term Ensuing REM may stabilize transformed While elaborated with respect hippocampus-dependent memories, concept redistribution networks serving temporary store stores might hold non-hippocampus-dependent memory, even nonneuronal, i.e., immunological giving rise idea offline represents principle formation quite different physiological systems.

Language: Английский

Citations

2495
Sleep and the Price of Plasticity: From Synaptic and Cellular Homeostasis to Memory Consolidation and Integration DOI Creative Commons
Giulio Tononi, Chiara Cirelli

Neuron, Journal Year: 2014, Volume and Issue: 81(1), P. 12 - 34

Published: Jan. 1, 2014

Language: Английский

Citations

2076
Synaptic Dysfunction in Depression: Potential Therapeutic Targets DOI
Ronald S. Duman,

George K. Aghajanian

Science, Journal Year: 2012, Volume and Issue: 338(6103), P. 68 - 72

Published: Oct. 4, 2012

Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions regulate mood cognition, including the prefrontal cortex hippocampus, decreased neuronal synapses in these areas. Antidepressants can block or reverse deficits, although typical antidepressants have limited efficacy delayed response times weeks to months. A notable recent discovery shows ketamine, a N -methyl- d -aspartate receptor antagonist, produces rapid (within hours) antidepressant responses patients who are resistant antidepressants. show ketamine rapidly induces synaptogenesis reverses synaptic deficits caused by chronic stress. These findings highlight central importance homeostatic control circuit connections form basis synaptogenic hypothesis treatment response.

Language: Английский

Citations

1342
Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy DOI
Mark J. Millan,

Y. Agid,

Martin Brüne

et al.

Nature Reviews Drug Discovery, Journal Year: 2012, Volume and Issue: 11(2), P. 141 - 168

Published: Feb. 1, 2012

Language: Английский

Citations

1162
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease DOI Creative Commons
Tara L. Spires‐Jones, Bradley T. Hyman

Neuron, Journal Year: 2014, Volume and Issue: 82(4), P. 756 - 771

Published: May 1, 2014

Language: Английский

Citations

1041
AMPARs and Synaptic Plasticity: The Last 25 Years DOI Creative Commons
Richard L. Huganir,

Roger A. Nicoll

Neuron, Journal Year: 2013, Volume and Issue: 80(3), P. 704 - 717

Published: Oct. 1, 2013

Language: Английский

Citations

903
Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain DOI

Tim Bliss,

Graham L. Collingridge, Bong‐Kiun Kaang

et al.

Nature reviews. Neuroscience, Journal Year: 2016, Volume and Issue: 17(8), P. 485 - 496

Published: June 16, 2016

Language: Английский

Citations

650
Pathogenic mechanisms following ischemic stroke DOI

Seyed Esmaeil Khoshnam,

William Winlow,

Maryam Farzaneh

et al.

Neurological Sciences, Journal Year: 2017, Volume and Issue: 38(7), P. 1167 - 1186

Published: April 17, 2017

Language: Английский

Citations

563
Anti-LGI1 encephalitis DOI
Agnes van Sonderen, Roland D. Thijs,

Elias C. Coenders

et al.

Neurology, Journal Year: 2016, Volume and Issue: 87(14), P. 1449 - 1456

Published: Sept. 3, 2016

This nationwide study gives a detailed description of the clinical features and long-term outcome anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.We collected patients prospectively from October 2013, retrospectively samples sent to our laboratory January 2007. LGI1 antibodies were confirmed with both cell-based assay immunohistochemistry. Clinical information was obtained in interviews their relatives medical records. Initial MRI follow-up revised blindly. Neuropsychological assessment performed those over 2 years.Annual incidence Netherlands 0.83/million. A total 34/38 had limbic encephalitis. Subtle focal seizures (66%, autonomic or dyscognitive) faciobrachial dystonic (FBDS, 47%) mostly occurred before onset memory disturbance. Later disease course, 63% tonic-clonic seizures. showed hippocampal T2 hyperintensity 74% patients. These lesions evolved regularly into mesial temporal sclerosis (44%). Substantial response immunotherapy seen 80%, early slow recovery cognition. At ≥2 years, most surviving reported mild residual cognitive deficit spatial disorientation. 86% persistent amnesia for period. Relapses common (35%) presented up 8 years after initial disease. Two-year case fatality rate 19%.Anti-LGI1 encephalitis is homogenous syndrome, showing FBDS other subtle manifestations, followed by disturbances. Better recognition will lead earlier diagnosis, essential prompt start treatment. Long-term favorable, but relapses are common.

Language: Английский

Citations

540
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels DOI Open Access
Kasper B. Hansen, Lonnie P. Wollmuth, Derek Bowie

et al.

Pharmacological Reviews, Journal Year: 2021, Volume and Issue: 73(4), P. 1469 - 1658

Published: Oct. 1, 2021

Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels critical to brain function and centrally implicated numerous psychiatric neurologic disorders. There different classes iGluRs with a variety receptor subtypes each class that play distinct roles neuronal functions. The diversity iGluR subtypes, their unique functional properties roles, has motivated large number studies. Our understanding advanced considerably since first subunit gene was cloned 1989, research focus expanded encompass facets biology have been recently discovered exploit experimental paradigms made possible technological advances. Here, we review insights from more than 3 decades studies an emphasis on progress occurred past decade. We cover structure, function, pharmacology, neurophysiology, therapeutic implications for all assembled subunits encoded 18 genes. SIGNIFICANCE STATEMENT: Glutamate important virtually aspects either involved mediating some clinical features neurological disease or represent target treatment. Therefore, pharmacology this will advance our many at molecular, cellular, system levels provide new opportunities treat patients.

Language: Английский

Citations

469