Introduction : Doublecortin (DCX) is a microtubule associated protein expressed by
migrating neural precursors. DCX is also expressed in approximately 4% of all cortical
cells in adult normal primate brain. DCX expression is also enhanced locally in response
to an acute insult made to the brain. This is thought to play a role in plasticity or neural
repair. That being said, it would be interesting to know how the expression of DCX is
modified in a more chronic insult, like in neurodegeneration such as in Parkinson's
Disease (PD) and Alzheimer's Disease (AD). The aim of my study is to study the
expression of DCX cells in the cortex of patients having a neurodegenerative
disease, compared to control patients.
Method: DCX cells quantification on 9 DCX‐stained 5 μm thick formalin fixed paraffin
embedded brain sections: 3 Alzheimer's disease patients, 3 Parkinson's disease patients
and 3 control patients. Each patient had several sections that we could stain with
different stainings (GALLYA, TAU, DCX). By using a computerized image analysis system
(Explora Nova, La Rochelle, France), cortical columns were selected on areas on the
cortex with a lot of degeneration subjectively observed on GALLYA stained sections and
on TAU stained sections. Then total number of cells was counted on TAU sections, where
all nuclei were colored in blue. Then the DCX cells were counted on the corresponding
DCX sections. These values were standardized to a reference surface area. The ratio of
DCX cells over total cells was then calculated.
Results : There is a difference of DCX cell expression between Alzheimer's Disease
patients and control patients. The percentage of dcx cells in the cortex of an Alzheimer's
patient is around 12.54% ± 2.17%, where as in the cortex of control patients, it is around
5.47% ± 0.83%.
On the other hand, there is no significant difference in the ratio of DCX cells over total
cells between parkinson's patients and control patients, both having around 5% of DCX
cells.
Discussion: There is a dramatic increase of DCX expression in AD (12.5%) compared to
PD and controls (5.5%). The increase in DCX ratio in AD may have two potential causes:
1.The increased ratio is due to DCX cells being more resistant to degeneration compared
to surrounding cells which are degenerating due to AD, leading to the cortical atrophy
observed in AD patients. So the decrease of total cells without any change in the number
of DCX cells makes the ratio bigger in AD compared to the controls.
2.The increased ratio is due to an actual increase in DCX cells. This means that there is
some neural repair to compensate the degenerative process, just like the repair process
observed in acute lesions to the brain.
This second idea can be integrated in the broader point of view of neuroinflammation.
The progression of the disease would trigger neuroinflammation and the process
following the primary inflammatory response which is neural repair. So our study can
show that the increase in DCX cells is an attempt to repair the degenerated neurons, in
the context of neuroinflammation triggered by the physiopathological progression of the
disease.