Abstract:
Parkinson’s disease (PD) is the second most common neurodegenerative disease. Patients with
PD experience a myriad of debilitating symptoms including ‘parkinsonian symptoms’ such as
resting tremor and bradykinesia. Neuropathologically, PD is characterised by neuronal loss in
the substantia nigra (SN), resulting in decreased dopaminergic innervation in the striatum.
However, studies investigating the role of non-neuronal cells in neurodegenerative disease is
increasingly important. Non-neuronal cells such as glia, including microglia and astrocytes act
to maintain homeostasis and can respond rapidly to insult and neuroinflammatory signals by
becoming ‘activated’. Post-mortem investigation of the PD SN has revealed increased glial
activation, whilst the role of glia in the PD striatum remains to be fully elucidated.
This study aimed to investigate microglia and astrocytes in the PD striatum by characterizing
glial immunoreactivity patterns and morphology in striatal sections from the Neurological
Foundation Human Brain Bank. Post-mortem human striatal tissue sections from n=8 PD and
n=8 control cases were subjected to free-floating immunohistochemical processes, utilising
antibodies: anti- Human Leukocyte Antigen–DR (HLA-DR) and anti- Ionized calciumbinding
adapter molecule 1 (Iba-1) for identification of microglia and anti- Glial fibrillary
acidic protein (GFAP) for identification of astrocytes. Processed sections were imaged with the
V-slide automated microscope. Automated image analysis software MetaMorphⓇ was used to
determine protein expression, cell count and morphology measurements for each glial
antibody.
No significant differences were found in Iba-1, HLA-DR or GFAP immunoreactivity patterns
or morphology, with the exception of a significant increase in the number of HLA-DR
processes, which may be indicative of microglial activation toward a hyper-ramified/
hypertrophic state. However, trending increases were seen in HLA-DR and GFAP
immunoreactivity patterns and morphology, which were not significant due to variable PD
data. High variability was demonstrated throughout the PD cohort for all three markers which
could be indicative of external factors or sub-groupings in the PD group. Larger sample sizes
should be applied in future studies, not only to fully encapsulate the extent of PD variability
and reveal any sub-groups, but also to validate any trending increases. Unveiling the role of
glia in PD neuropathology allows for greater understanding of pathological processes.