Laboratory of Neuroendocrinology and Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, Slovenia.
Celica, BIOMEDICAL, Ljubljana, Slovenia.
FEBS J. 2018 Oct;285(19):3645-3656. doi: 10.1111/febs.14456. Epub 2018 Apr 16.
Impairment of the main noradrenergic nucleus of the human brain, the locus coeruleus (LC), which has been discovered in 1784, represents one of defining factors of neurodegenerative diseases progression. Projections of LC neurons release noradrenaline/norepinephrine (NA), which stimulates astrocytes, homeostatic neuroglial cells enriched with adrenergic receptors. There is a direct correlation between the reduction in noradrenergic innervations and cognitive decline associated with ageing and neurodegenerative diseases. It is, therefore, hypothesized that the resilience of LC neurons to degeneration influences the neural reserve that in turn determines cognitive decline. Deficits in the noradrenergic innervation of the brain might be reversed or restrained by increasing the activity of existing LC neurons, transplanting noradrenergic neurons, and/or using drugs that mimic the activity of NA on astroglia. Here, these strategies are discussed with the aim to understand how astrocytes integrate neuronal network activity in the brain information processing in health and disease.
1784 年发现的人类大脑主要去甲肾上腺素能核——蓝斑（LC）的损伤，是神经退行性疾病进展的决定性因素之一。LC 神经元的投射释放去甲肾上腺素/正肾上腺素（NA），刺激富含肾上腺素能受体的星形胶质细胞，即神经胶质细胞。去甲肾上腺素能神经支配的减少与衰老和神经退行性疾病相关的认知能力下降之间存在直接的相关性。因此，人们假设 LC 神经元对变性的适应能力会影响决定认知能力下降的神经储备。通过增加现有 LC 神经元的活性、移植去甲肾上腺素能神经元和/或使用模拟 NA 对星形胶质细胞活性的药物，可能逆转或抑制大脑去甲肾上腺素能神经支配的不足。在这里，讨论了这些策略，目的是了解星形胶质细胞如何在健康和疾病中整合神经元网络活动进行大脑信息处理。
