Short-term behavioral alterations are associated with infection and aid the recovery from sickness.
However, concerns have raised that sustained behavioral disturbances after acute neuroinflammation
could relate to neurological diseases in the long run. We aimed to explore medium- and longterm
behavioral disturbances after acute neuroinflammation in rats, using a model based on the
intracerebroventricular administration of the enzyme neuraminidase (NA), which is part of some
pathogenic bacteria and viruses. Neurological and behavioral assessments were performed 2 and
10 weeks after the injection of NA, and neuroinflammation was evaluated by gene expression and
histology. No alterations were observed regarding basic neurological functions or locomotor capacity
in NA-injected rats. However, they showed a reduction in unsupported rearing, and increased
grooming and freezing behaviors, which indicate anxiety-like behavior. A principal component
analysis including a larger set of parameters further supported such anxiety-like behavior. The
anxiety profile was observed 2 weeks after NA-injection, but not after 10 weeks. Concomitantly, the
amygdala presented increased number of microglial cells showing a morphologic bias towards an
activated state. A similar but subtler tendency was observed in hypothalamic microglia located in the
paraventricular nucleus. Also, in the hypothalamus the pattern recognition receptor toll-like receptor
4 (TLR4) was slightly overexpressed 2 weeks after NA injection. These results demonstrate that
NA-induced neuroinflammation provokes anxiety-like behavior in the medium term, which disappears
with time. Concurrent microgliosis in the amygdala could explain such behavior. Further experiments
should aim to explore subtle but long-lasting alterations observed 10 weeks after NA injection, both in
amygdala and hypothalamus, as well as mild behavioral changes.
