Fornai Francesco, Puglisi-Allegra Stefano
Department of Translational Research and New Technologies on Medicine and Surgery, University of Pisa, Via Roma 55, Pisa, PI, 56126, Italy; IRCCS Neuromed, Via Atinense 18, Pozzilli, IS, Italy.
IRCCS Neuromed, Via Atinense 18, Pozzilli, IS, Italy.
Neurosci Biobehav Rev. 2021 Apr;123:238-256. doi: 10.1016/j.neubiorev.2021.01.015. Epub 2021 Jan 23.
The catecholamine-containing brainstem nuclei locus coeruleus (LC) and ventral tegmental area (VTA) are critically involved in stress responses. Alterations of catecholamine systems during chronic stress may contribute to neurodegeneration, including cognitive decline. Stress-related catecholamine alterations, while contributing to anxiety and depression, might accelerate neuronal degeneration by increasing the formation of toxic dopamine and norepinephrine by-products. These, in turn, may impair proteostasis within a variety of cortical and subcortical areas. In particular, the molecular events governing neurotransmission, neuroplasticity, and proteostasis within LC and VTA affect a variety of brain areas. Therefore, we focus on alterations of autophagy machinery in these nuclei as a relevant trigger in this chain of events. In fact, these catecholamine-containing areas are mostly prone to autophagy-dependent neurodegeneration. Thus, we propose a dynamic hypothesis according to which stress-induced autophagy alterations within the LC-VTA network foster a cascade towards early neurodegeneration within these nuclei.
含儿茶酚胺的脑干核团蓝斑（LC）和腹侧被盖区（VTA）在应激反应中起关键作用。慢性应激期间儿茶酚胺系统的改变可能导致神经退行性变，包括认知能力下降。与应激相关的儿茶酚胺改变在导致焦虑和抑郁的同时，可能通过增加有毒多巴胺和去甲肾上腺素副产物的形成来加速神经元变性。反过来，这些可能会损害各种皮质和皮质下区域的蛋白质稳态。特别是，在LC和VTA内控制神经传递、神经可塑性和蛋白质稳态的分子事件会影响多个脑区。因此，我们将重点关注这些核团中自噬机制的改变，将其作为这一系列事件中的一个相关触发因素。事实上，这些含儿茶酚胺的区域最容易发生自噬依赖性神经退行性变。因此，我们提出了一个动态假说，即应激诱导的LC-VTA网络内的自噬改变会引发一系列反应，导致这些核团内早期神经退行性变。
