South African Psychiatry - February 2019

REPORT
is focused on neurodevelopmental influences
towards depression and neurodegenerative
diseases studied in animal models.
His seminar was on ‘Brainstem Dysfunction in
Neuropsychiatric Disorders’ such as Alzheimer’s
Disease, Parkinson’s Disease and depression.
Despite the fundamental role of the brainstem in
regulating vital functional abilities such as arousal,
breathing, autonomic nervous system activity as
well as regulating all higher cerebral functions via
neurotransmitter projection systems originating in
the brainstem, the role of the brainstem has received
relatively little attention in most neuropsychiatric
disorders. His seminar reviewed 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).
Besides the dorsal and median raphe nuclei
complexes comprising mainly of serotoninproducing
neurons, the brainstem also contains
noradrenalin, dopamine and histamine-producing
nuclei, i.e. the locus coeruleus, the substantia
nigra and the mamillary bodies respectively. The
brainstem is furthermore the relay station of afferent
and efferent projections between the autonomic
nervous system in the peripheral body and higher
cerebral brain regions.
Over the past decades, the incidence of agerelated,
neurological and psychiatric disorders such
as Alzheimer’s disease, Parkinson’s disease, but
also depression has increased considerably. Mood
disorders are strongly related to exposure to stress.
THE HIPPOCAMPUS AND OTHER
FOREBRAIN STRUCTURES ARE THE
APEX OF STRESS HORMONE CONTROL
MECHANISMS AND DAMAGE TO THEM
MAY BE ONE WAY IN WHICH STRESS
HORMONE SECRETION ESCAPES FROM
INHIBITORY CONTROL IN DEPRESSION.
In turn, stress, probably through toxic effects of
glucocorticoids, decreases neurogenesis and
cell survival while antidepressants enhance these
processes in experimental animals. Therefore,
since treatment strategies are not yet available,
primary prevention in these age-related and stressrelated
neurological disorders is of importance.
As mentioned before most of the focus on
neurobiological questions on the above mentioned
diseases are related to forebrain structures since
they are often associated with cognitive dysfunction.
The brainstem is a highly neglected brain area in
neurodegenerative diseases, including Alzheimer’s
and Parkinson’s disease and frontotemporal lobar
degeneration. Likewise, despite a long-standing
recognition of brainstem involvement, relatively few
studies have addressed the exact mechanisms that
underlie brainstem autonomic dysfunction. Improved
insight in the cellular and molecular characteristics of
brainstem function is pivotal to study developmental
origins. In the area of depression, several observations
have been made in relation to changes in one
particular brain structure: the dorsal raphe nucleus.
In addition, dysfunction of the cerebellum is also
observed in Alzheimer’s disease and associated with
pulmonary deregulation. The dorsal raphe nucleus
is also involved in the circuit of stress regulated
processes and cognitive events. In order to gain
more information about the underlying mechanisms
that may govern neurodegeneration, e.g. amyloid
plaques, neurofibrillary tangles, and impaired
synaptic transmission in Alzheimer’s disease, a rat
dissociation culture model was established by Prof
Steinbusch and his colleagues that allows mimicking
of certain aspects of autopsy findings. They observed
a similar phenomenon in brains from patients
suffering from neurodegenerative disease since this
also related to changes in brain derived neurotropic
factor (BDNF) levels. The ascending projections and
multi-transmitter nature of the dorsal raphe nucleus
in particular and the brainstem in general stress its
role as a key target for research into Alzheimer’s and
Parkinson’s disease and autonomic dysfunction.
It also points towards the increased importance
and focus of the brainstem as a key area in various
neurodevelopmental and age-related diseases.
Prof Steinbusch taking questions from the audience.
Profs. Steinbusch and Tremblay with Wits Cortex Club members, students and staff
members.
Tanya Calvey has a background in evolutionary neurobiology and lectures morphological anatomy in the Faculty of Health
Sciences, University of the Witwatersrand. Tanya studies the neuropsychopharmacology of SUDs in humans and animals.
Her research team is multidisciplinary and her research is funded by the South African Medical Research Council, the
National Research Foundation and the International Society for Neurochemistry. Tanya is also actively involved in developing
neuroscience research in Africa. She is the Secretary of the Southern African Neuroscience Society and the co-founder of the
Wits Cortex Club. Correspondence: Tanya.Calvey@wits.ac.za
54 * SOUTH AFRICAN PSYCHIATRY ISSUE 18 2019