South African Psychiatry - February 2019

REPORT
CELLULAR
NEUROSCIENCE
OF PSYCHIATRIC
DISORDERS
Tanya Calvey
On the 23 rd of November, 2018, the Wits
Cortex Club hosted two prominent
neuroscientists (Profs. Harry Steinbusch
and Marie-Ève Tremblay) to address
the Wits Faculty of Health Sciences on cellular
mechanisms involved in various psychiatric
disorders. The lunch time seminar took place in
the Adler Museum of Medicine and was funded
by the National Research Foundation and the Wits
Department of Psychiatry.
Marie-Ève Tremblay is an Associate Professor of
Molecular Medicine at Université Laval, Québec,
Canada. Her research focuses on elucidating the
roles of microglia in the loss of synapses, which
is one of the best pathological correlates of
cognitive decline across chronic stress, aging, and
neurodegenerative diseases.
Her seminar ‘Dark microglia across contexts of health
and disease’ uncovered the recent characterization
by her laboratory of an ultra-structurally distinct
microglial subtype that is predominantly associated
with pathological states. These cells are rare in
steady state conditions, but become prevalent
upon chronic stress, aging, and Alzheimer’s disease
pathology, where they account for two-thirds of the
normal microglial population. They exhibit several
signs of cellular stress including a condensed,
electron-dense cytoplasm and nucleoplasm giving
them a ‘dark’ appearance in electron microscopy,
accompanied by endoplasmic reticulum dilation,
mitochondrial alterations, and a loss of nuclear
heterochromatin pattern. The physiological
significance of these dark
microglia has yet to be elucidated
but they appear extremely active,
frequently reaching for synaptic
clefts, while extensively encircling
axon terminals, dendritic spines,
and excitatory synapses with their
highly ramified and extremely thin
processes. In addition, her recent
work revealed the occurrence
Tanya Calvey
of these dark microglia in a
schizophrenia mouse model induced by a prenatal
immunological challenge, as well as in early
postnatal brain development, two conditions where
synaptic pruning is exacerbated.
THESE FINDINGS INDICATE THAT DARK
MICROGLIA COULD REPRESENT A SUBSET
OF CELLS THAT BECOME STRESSED
AS A RESULT OF THEIR HYPERACTIVE
INVOLVEMENT WITH THE REMODELING
OF NEURONAL CIRCUITS ACROSS
DEVELOPMENT, PLASTICITY, AND DISEASE.
Prof. Harry Steinbusch is appointed as Professor in
Cellular Neuroscience, chairman of the Department
of Translational Neuroscience, past-director of the
School for Mental Health and Neuroscience, current
Director of the European Graduate School for
Neuroscience at Maastricht University and President
of the Neurotoxicity Society. He is the founding editor of
the Journal of Chemical Neuroanatomy. His research
SOUTH AFRICAN PSYCHIATRY ISSUE 18 2019 * 53