scholarly journals Disruption of Exocytosis in Sympathoadrenal Chromaffin Cells from Mouse Models of Neurodegenerative Diseases

2020 ◽  
Vol 21 (6) ◽  
pp. 1946
Author(s):  
Antonio M. G. de Diego ◽  
Diana Ortega-Cruz ◽  
Antonio G. García

Synaptic disruption and altered neurotransmitter release occurs in the brains of patients and in murine models of neurodegenerative diseases (NDDs). During the last few years, evidence has accumulated suggesting that the sympathoadrenal axis is also affected as disease progresses. Here, we review a few studies done in adrenal medullary chromaffin cells (CCs), that are considered as the amplifying arm of the sympathetic nervous system; the sudden fast exocytotic release of their catecholamines—stored in noradrenergic and adrenergic cells—plays a fundamental role in the stress fight-or-flight response. Bulk exocytosis and the fine kinetics of single-vesicle exocytotic events have been studied in mouse models carrying a mutation linked to NDDs. For instance, in R6/1 mouse models of Huntington’s disease (HD), mutated huntingtin is overexpressed in CCs; this causes decreased quantal secretion, smaller quantal size and faster kinetics of the exocytotic fusion pore, pore expansion, and closure. This was accompanied by decreased sodium current, decreased acetylcholine-evoked action potentials, and attenuated [Ca2+]c transients with faster Ca2+ clearance. In the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), CCs exhibited secretory single-vesicle spikes with a slower release rate but higher exocytosis. Finally, in the APP/PS1 mouse model of Alzheimer’s disease (AD), the stabilization, expansion, and closure of the fusion pore was faster, but the secretion was attenuated. Additionally, α-synuclein that is associated with Parkinson’s disease (PD) decreases exocytosis and promotes fusion pore dilation in adrenal CCs. Furthermore, Huntington-associated protein 1 (HAP1) interacts with the huntingtin that, when mutated, causes Huntington’s disease (HD); HAP1 reduces full fusion exocytosis by affecting vesicle docking and controlling fusion pore stabilization. The alterations described here are consistent with the hypothesis that central alterations undergone in various NDDs are also manifested at the peripheral sympathoadrenal axis to impair the stress fight-or-flight response in patients suffering from those diseases. Such alterations may occur: (i) primarily by the expression of mutated disease proteins in CCs; (ii) secondarily to stress adaptation imposed by disease progression and the limitations of patient autonomy.

2019 ◽  
Vol 40 (1) ◽  
pp. 014002 ◽  
Author(s):  
Amin Derakhshan ◽  
Mohammad Mikaeili ◽  
Ali Motie Nasrabadi ◽  
Tom Gedeon

2018 ◽  
Vol 108 ◽  
pp. 1404-1411
Author(s):  
Mahsa Rahmani ◽  
Mousa Mohammadnia-Afrouzi ◽  
Hamid Reza Nouri ◽  
Sadegh Fattahi ◽  
Haleh Akhavan-Niaki ◽  
...  

Science ◽  
1995 ◽  
Vol 270 (5236) ◽  
pp. 644-646 ◽  
Author(s):  
A. S. P. Jansen ◽  
X. V. Nguyen ◽  
V. Karpitskiy ◽  
T. C. Mettenleiter ◽  
A. D. Loewy

Author(s):  
Angela Duckworth ◽  

For more than a century, scientists have known that acute stress activates the fight-or-flight response. When your life is on the line, your body reacts instantly: your heart races, your breath quickens, and a cascade of hormones sets off physiological changes that collectively improve your odds of survival. More recently, scientists have come to understand that the fight-or-flight response takes a toll on the brain and the body—particularly when stress is chronic rather than acute. Systems designed to handle transient threats also react to stress that occurs again and again, for weeks, months, or years. It turns out that poverty, abuse, and other forms of adversity repeatedly activate the fight-or-flight response, leading to long-term effects on the immune system and brain, which in turn increase the risk for an array of illnesses, including asthma, diabetes, arthritis, depression, and cardiovascular disease. Pioneering neuroscientist Bruce McEwen called this burden of chronic stress “allostatic load.”


Author(s):  
David Anthony Pittaway

The Covid-19 pandemic accelerated the global trend towards spending increasing amounts of time online. I explore some of the potential negative consequences of lockdown-induced increases in time spent online, and I argue that the stressful context of the pandemic and lockdowns is exacerbated by being online beyond that which is required for essential purposes. Time spent online may increase stress levels by perpetuating the sympathetic nervous system's fight-or-flight response, draining a person’s energy and diminishing one’s ability to deal with illness. I frame the situation as one in which the pandemic context, combined with a mandatory need to be online more, forces many people into what Daniel Kahneman calls “System 1 thinking”, or “fast thinking”. I argue that digital hygiene requires the suspension of System 1 thinking, and that “philosophical perception” resonates with potential remedies in this regard.


2019 ◽  
Vol 597 (15) ◽  
pp. 3867-3883 ◽  
Author(s):  
Lianguo Wang ◽  
Stefano Morotti ◽  
Srinivas Tapa ◽  
Samantha D. Francis Stuart ◽  
Yanyan Jiang ◽  
...  

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