Note: This research concerns ALS, but also associates this particular research to SBMA (Kennedy's Disease) Article found on 7th Space Interactive
The peripheral immune system is implicated in modulating microglial
activation, neurodegeneration and disease progression in amyotrophic
lateral sclerosis (ALS). Specifically, there is reduced thymic function
and regulatory T cell (Treg) number in ALS patients and mutant
superoxide dismutase 1 (SOD1) mice, while passive transfer of Tregs
ameliorates disease in mutant SOD1 mice.
Here, we assessed the
effects of augmenting endogenous CD4+ T cell number by stimulating the
thymus using surgical castration on the phenotype of transgenic SOD1G93A
mice.MethodMale SOD1G93A mice were castrated or sham operated, and
weight loss, disease onset and progression were examined. Thymus atrophy
and blood CD4+, CD8+ and CD4+ FoxP3+ T cell numbers were determined by
fluorescence activated cell sorting (FACS).
Motor neuron counts,
glial cell activation and androgen receptor (AR) expression in the
spinal cord were investigated using immunohistochemistry and Western
blotting. Differences between castrated and sham mice were analysed
using an unpaired t test or one-way ANOVA.
Castration significantly increased thymus weight and total CD4+ T cell
numbers in SOD1G93A mice, although Tregs levels were not affected.
Despite this, disease onset and progression were similar in castrated
and sham SOD1G93A mice. Castration did not affect motor neuron loss or
astrocytic activation in spinal cords of SOD1G93A mice; however,
microglial activation was reduced, specifically M1 microglia.
also show that AR is principally expressed in spinal motor neurons and
progressively downregulated in spinal cords of SOD1G93A mice from
disease onset which is further enhanced by castration.
These results demonstrate that increasing thymic function and CD4+ T
cell number by castration confers no clinical benefit in mutant SOD1
mice, which may reflect an inability to stimulate neuroprotective Tregs.
Nonetheless, castration decreases M1 microglial activation in the
spinal cord without any clinical improvement and motor neuron rescue, in
contrast to other approaches to suppress microglia in mutant SOD1 mice.
Lastly, diminished AR expression in spinal motor neurons, which links
to another motor neuron disorder, spinal bulbar muscular atrophy (SBMA),
may contribute to ALS pathogenesis and suggests a common disease
pathway in ALS and SBMA mediated by disruption of AR signalling in motor
Author: Rebecca K SheeanRichard H WestonNirma D PereraAngela Dâ€™AmicoStephen L NuttBradley J Turner - Credits/Source: Journal of Neuroinflammation 2015, 12:40
Published on: 2015-02-27 -
News Provider: 7thSpace Interactive / EUPB Press Office
Copyright by the authors listed above - made available via BioMedCentral (Open Access).