Stressor-induced Neurochemical
Changes: Genetic & Ontogenetic Factors
Communication may occur between the immune and central
nervous system, and cytokines (signaling molecules of the immune system) may
act as messengers (immunotransmitters) in this respect. The immune system
may act like a sensory organ informing the brain of antigenic challenge, and
given the nature of the neurochemical changes elicited by cytokines, immune
activation may be interpreted by the CNS as a stressor. It has been our contention
that the immune system may be part of a regulatory loop that, by virtue of
its effects on CNS functioning, might contribute to the symptoms of behavioral
pathologies, including mood and anxiety-related disorders, and may contribute
to cognitive disturbances frequently seen during immunotherapy in cancer patients.
Several macrophage-derived cytokines, such as interleukin
(IL)-1b, IL-6, and tumor necrosis factor-a (TNF-a), as well as IL-2 secreted
from T-helper cells, may be particularly important in subserving immune-brain
communication. The objective of this aspect of our research program is to
elucidate the potential neurochemical and behavioral sequelae of immune and
cytokine challenge. Our ongoing research (supported by CIHR), using rats,
assesses the effects of systemic and central cytokine administration (e.g.,
IL-1b, IL-6, TNF-a) on in vivo (by microdialysis) central monoamine and neuropeptide
activity in brain regions where stressors ordinarily have profound effects.
As well, we assess whether synergistic behavioral, neuroendocrine and neurotransmitter
effects occur between cytokines and stressors, and whether cytokine activation
induces a sensitization effect so that subsequent responses to either cytokine
treatment or stressor challenges are enhanced.
If cytokines play a role in affective illness, then
it would be expected that cytokine challenge (like stressors) will induce
behavioral changes reminiscent of depressive symptomatology (e.g., anhedonia)
and will provoke anxiogenic effects. Thus, the neurochemical effects of stressors
are paralleled by studies to assess the behavioral effects of cytokine treatments.
These include several tests of anhedonia, exploratory profiles, sickness behaviors,
working and reference memory changes, as well as several different tests of
anxiety.
Supported by CIHR
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