Novel views on brainstem structure and function and their implications in brain disorders

Abstract

The brainstem as the evolutionary oldest part of the brain plays a pivotal role in the regulation of cardiac and respiratory function. It regulates the central nervous system, and maintains consciousness and regulates the sleep cycle. Despite these fundamental roles of the brainstem in regulating vital functional abilities such as autonomic nervous system activity as well as regulating all higher cerebral functions via neurotransmitter projections systems originating in the brainstem, the role of the brainstem is mostly neglected in most neuropsychiatric disorders. Besides the dorsal and median raphe nuclei complex comprising mainly serotonin-producing neurons, the brainstem also contains noradrenalin, dopamine and histamine-producing nuclei, i.e. resp. the Locus Coeruleus, the Substantia Nigra and the Mamillary Bodies. Most of the focus on neurobiological questions on above mentioned disease are related to forebrain structures since they are often associated with cognitive dysfunction. As a consequence the brainstem has been highly neglected in neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s (PD) disease and frontotemporal lobar degeneration. In the area of depression, several observations have been made in relation to changes in one particular brain structure: the Dorsal Raphe Nucleus (DRN). In addition dysfunction of the cerebellum is also observed in AD and associated with pulmonary deregulation. The DRN is also related in the circuit of stress regulated processes and cognitive events. The ascending projections and multitransmitter nature of the DRN in particular and the brainstem in general stress its role as a key target for AD/PD research and autonomic dysfunction. It also points towards the increased importance and focus of the brainstem as key area in various neurodevelopmental and age-related diseases. The current presentation aims to review the neuroanatomy of the brainstem as well as the current status on findings, derived from a wide range of studies using molecular, cellular and imaging technologies, of brainstem involvement in neurodevelopmental (i.e. autism, schizophrenia) and neurodegenerative disorders (Alzheimer’s and Parkinson’s disease).