Related Experiment Video
Updated: Oct 4, 2025
08:16
Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
Published on: June 17, 2015
18.5K
Amyloid-β oligomers in the nucleus accumbens decrease motivation via insertion of calcium-permeable AMPA receptors
Changyong Guo1, Di Wen1, Yihong Zhang1
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Molecular Psychiatry
|February 2, 2022
Summary
Alzheimer's Disease (AD) linked apathy may stem from abnormal brain activity in the nucleus accumbens. Blocking specific receptors prevents synaptic damage and motivation loss, offering a potential therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Neuropsychiatric symptoms like apathy are common in Alzheimer's Disease (AD).
- The nucleus accumbens (NAc), crucial for motivation, shows AD-related pathology.
- Understanding NAc's role in AD is vital for patient quality of life.
Purpose of the Study:
- To investigate the neuronal mechanisms underlying AD-associated neuropsychiatric symptoms in the NAc.
- To identify the role of synaptic receptors in AD-induced synaptic degeneration and motivation deficits.
Main Methods:
- Examined the presence and function of calcium-permeable (CP)-AMPA receptors (AMPARs) in the NAc.
- Utilized amyloid-beta oligomers (AβOs) to model AD pathology.
- Assessed the effects of blocking NAc CP-AMPARs on synaptic structure and function.
Main Results:
- Normally absent CP-AMPARs were detected in the NAc upon exposure to AβOs.
- AβO-induced CP-AMPARs were critical for synaptic loss and motivation deficits.
- Blocking NAc CP-AMPARs prevented AβO-induced synaptic pruning and dysfunction.
Conclusions:
- AβO-triggered synaptic insertion of CP-AMPARs is a key mechanism in AD synaptic degeneration.
- Preserving synaptic integrity in the NAc may prevent or delay AD-associated psychiatric symptoms.
Related Concept Videos
01:30Regulation of Food Intake
791
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
791
01:16Calmodulin-dependent Signaling
5.4K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.4K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.9K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.9K
03:03Amyloid Fibrils
10.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
10.5K
01:26Neurochemical Transmission: Sites of Drug Action
2.8K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.8K
01:27Adrenergic Neurons: Neurotransmission
4.4K
Postganglionic sympathetic fibers (except those supplying the sweat glands) releasing noradrenaline or norepinephrine are called noradrenergic or adrenergic neurons. Noradrenaline, dopamine, adrenaline, or epinephrine are collectively called "catecholamines" as they contain a catechol moiety and an amine side chain. The five stages of neurotransmitter release involve their synthesis, storage, release, reuptake and metabolism.
Synthesis: Catecholamine synthesis requires tyrosine, which...
Synthesis: Catecholamine synthesis requires tyrosine, which...
4.4K