Rett Syndrome, such as respiration and cognition, we hypothesize that the locus coeruleus is a critical site at which loss of MECP2 results in CNS dysfunction. Restoration of normal locus ceruleus function may therefore be of potential therapeutic value in the treatment of Rett Syndrome." This could explain why a norepinephrine reuptake inhibitor (desipramine, DMI), which enhances the extracellular NE levels at all noradrenergic synapses, ameliorated some Rett syndrome symptoms in a mouse model of Rett syndrome. Neurodegenerative diseases The locus ceruleus is affected in many forms of neurodegenerative diseases: genetic and idiopathic Parkinson's disease, progressive supranuclear palsy, Pick's disease or Alzheimer's disease. It is also affected in Down syndrome. For example, there is up to 80% loss of locus ceruleus neurons in Alzheimer's disease, Mouse models of Alzheimer's disease show accelerated progression after chemical destruction of the locus ceruleus, and neurofibrillary tangles, a primary biomarker of Alzheimer's disease, may be found in the locus ceruleus decades before any clinical symptoms. The norepinephrine from locus ceruleus cells in addition to its neurotransmitter role locally diffuses from "varicosities". As such it provides an endogenous anti-inflammatory agent in the microenvironment around the neurons, glial cells, and blood vessels in the neocortex and hippocampus. It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokines and promotes phagocytosis of Aβ. This suggests that degeneration of the locus ceruleus might be responsible for increased Aβ deposition in AD brains. Degeneration of pigmented neurons in this region in Alzheimer's and Parkinson's disease can be visualized in vivo with Neuromelanin MRI. Since the marked degeneration of locus coeruleus, and the neuroprotective properties of noradrenaline, Ian Robertson proposed the "Noradrenergic Theory of Cognitive Reserve" which postulates that the upregulation of the locus coeruleus-noradrenergic system throughout the lifespan may enhance cognitive stimulation contributing to cognitive reserve preventing from neurodegeneration. Recent evidence appear to support this theory reporting the locus coeruleus integrity primarily responsible of biological brain maintenance, cognitive efficiency, and reduced neuropathological burden. Sleep deprivation Animal studies showed that sleep deprivation can reduce the number of neurons in the locus coeruleus. Therefore the possibility of lasting damages to human brain functions due to sleep deprivation has become a matter of discussion. History The locus coeruleus was discovered in 1784 by Félix Vicq-d'Azyr, redescribed later by Johann Christian Reil in 1809 and named by the brothers Joseph and Karl Wenzel in 1812. High monoamine oxidase