Douglas L. Feinstein, Sergey Kalinin and David Braun
The classical neurotransmitter noradrenaline (NA) has critical roles in modulating behaviors including those involved in sleep, anxiety, and depression. However, NA can also elicit anti-inflammatory responses in glial cells, can increase neuronal viability by inducing neurotrophic factor expression, and can reduce neuronal damage due to oxidative stress by scavenging free radicals. NA is primarily produced by tyrosine hydroxylase (TH) expressing neurons in the locus coeruleus (LC), a relatively small brainstem nucleus near the IVth ventricle which sends projections throughout the brain and spinal cord. It has been known for close to 50 years that LC neurons are lost during normal aging, and that loss is exacerbated in neurological diseases including Parkinson's disease and Alzheimer's disease. LC neuronal damage and glial activation has now been documented in a variety of other neurological conditions and diseases, however, the causes of LC damage and cell loss remain largely unknown. A number of approaches have been developed to address the loss of NA and increased inflammation associated with LC damage, and several methods are being explored to directly minimize the extent of LC neuronal cell loss or function. In this review, we will summarize some of the consequences of LC loss, consider several factors that likely contribute to that loss, and discuss various ways that have been used to increase NA or to reduce LC damage.