The postmortem human brain as a tool to study central nervous system disease

Abnormalities in noradrenergic transmission are likely to play a role in behavioral expressions of a number of psychiatric and neurological disorders. The extent to which these abnormalities are pathognomonic, or even principal pathological features contributing to the illness, remains debatable. Interest in the potential for pathological abnormalities in central norepinephrine in central nervous system (CNS) disorders derives from the three general observations: (1) disruption of behaviors known to be heavily influenced by noradrenergic transmission that are associated with the illness; (2) demonstration that pharmacological manipulation of noradrenergic transmission can precipitate, modify, or alleviate symptoms of these disorders; and (3) certain CNS disorders are characterized pathologically by a loss of noradrenergic neurons in the brain. Research on the pathology of central noradrenergic systems in CNS diseases and their relationship to behavioral alterations utilizes a variety of techniques, most of which are technically indirect, given that we currently are unable to directly measure noradrenergic neuron activity, noradrenergic receptor signaling, or norepinephrine release in vivo in living humans. In vivo imaging methods now permit investigators to measure occupancy of certain receptors, but application of these methods specifically to noradrenergic proteins, such as receptors, enzymes or transporters, has been limited.

One method to study the role of norepinephrine in the CNS disorders is to utilize postmortem brain tissue from subjects with a given psychiatric or neurological condition.