Extracellular ATP Neurotransmission and Nicotine Sex-Specifically Modulate Habenular Neuronal Activity in Adolescence.

The recent increase in the use of nicotine products by teenagers has revealed an urgent need to better understand the impact of nicotine on the adolescent brain. Here, we sought to examine the actions of extracellular ATP as a neurotransmitter and to investigate whether ATP and nicotinic signaling interact during adolescence. With the GRAB (G-protein-coupled receptor activation-based ATP sensor), we first demonstrated that nicotine induces extracellular ATP release in the medial habenula, a brain region involved in nicotine aversion and withdrawal.

Intracellular Injection of Brain Extracts from Alzheimer's Disease Patients Triggers Unregulated Ca Release from Intracellular Stores That Hinders Cellular Bioenergetics.

Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer's disease (AD) by promoting uncontrolled elevation of cytosolic Ca in neurons. We have previously shown that synthetic Aβ42 oligomers stimulate abnormal intracellular Ca release from the endoplasmic reticulum stores, suggesting that a similar mechanism of Ca toxicity may be common to the endogenous Aβs oligomers. Here, we use human postmortem brain extracts from AD-affected patients and test their ability to trigger Ca fluxes when injected intracellularly into Xenopus oocytes.

Upregulated Ca Release from the Endoplasmic Reticulum Leads to Impaired Presynaptic Function in Familial Alzheimer's Disease.

Neurotransmitter release from presynaptic terminals is primarily regulated by rapid Ca influx through membrane-resident voltage-gated Ca channels (VGCCs). Moreover, accumulating evidence indicates that the endoplasmic reticulum (ER) is extensively present in axonal terminals of neurons and plays a modulatory role in synaptic transmission by regulating Ca levels. Familial Alzheimer's disease (FAD) is marked by enhanced Ca release from the ER and downregulation of Ca buffering proteins.

Quantifying the dose-dependent impact of intracellular amyloid beta in a mathematical model of calcium regulation in xenopus oocyte.

Alzheimer's disease (AD) is a devastating illness affecting over 40 million people worldwide. Intraneuronal rise of amyloid beta in its oligomeric forms (iAβOs), has been linked to the pathogenesis of AD by disrupting cytosolic Ca2+ homeostasis. However, the specific mechanisms of action are still under debate and intense effort is ongoing to improve our understanding of the crucial steps involved in the mechanisms of AβOs toxicity.

PunctaSpecks: A tool for automated detection, tracking, and analysis of multiple types of fluorescently labeled biomolecules.

Recent advances in imaging technology and fluorescent probes have made it possible to gain information about the dynamics of subcellular processes at unprecedented spatiotemporal scales. Unfortunately, a lack of automated tools to efficiently process the resulting imaging data encoding fine details of the biological processes remains a major bottleneck in utilizing the full potential of these powerful experimental techniques. Here we present a computational tool, called PunctaSpecks, that can characterize fluorescence signals arising from a wide range of biological molecules under normal and pathological conditions.