Novel application of behavioral assays allows dissociation of joint pathology from systemic extra-articular alterations induced by inflammatory arthritis
2016
Introduction: Although rheumatoid arthritis (RA) is a disease of
articular joints, patients often suffer from co-morbid neuropsychiatric
changes, such as anxiety, that may reflect links between
heightened systemic inflammation and abnormal regulation of
the hypothalamic-pituitary-adrenal (HPA) axis. Here, we apply
behavioral neuroscience methods to assess the impact of antigeninduced
arthritis (AIA) on behavioral performance in wild type (WT)
and interleukin-10 deficient (Il10-/-) mice. Our aim was to identify
limb-specific motor impairments, as well as neuropsychological
responses to inflammatory arthritis.
Methods: Behavioral testing was performed longitudinally in
WT and Il10-/- mice before and after the induction of arthritic
joint pathology. Footprint analysis, beam walking and open field
assessment determined a range of motor, exploratory and anxietyrelated
parameters. Specific gene changes in HPA axis tissues
were analyzed using qPCR.
Results: Behavioral assessment revealed transient motor and
exploratory impairments in mice receiving AIA, coinciding with joint
swelling. Hind limb coordination deficits were independent of joint
pathology. Behavioral impairments returned to baseline by 10 days
post-AIA in WT mice. Il10-/- mice demonstrated comparable levels
of swelling and joint pathology as WT mice up to 15 days post-AIA,
but systemic differences were evident in mRNA expression in HPA
axis tissues from Il10-/- mice post-AIA. Interestingly, the behavioral
profile of Il10-/- mice revealed a significantly longer time post-AIA for
activity and anxiety-related behaviors to recover.
Conclusions: The novel application of sensitive behavioral tasks
has enabled dissociation between behaviors that occur due to
transient joint-specific pathology and those generated by more
subtle systemic alterations that manifest post-AIA.
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