Time-dependent sensitization of corticotropin-releasing hormone, arginine vasopressin and c-fos immunoreactivity within the mouse brain in response to tumor necrosis factor-alpha
S. Hayley et al., Time-dependent sensitization of corticotropin-releasing hormone, arginine vasopressin and c-fos immunoreactivity within the mouse brain in response to tumor necrosis factor-alpha, NEUROSCIENC, 106(1), 2001, pp. 137-148
Stressor or cytokine treatments, such as interleukin-1 beta, promote time-d
ependent alterations of hypothalamic-pituitary-adrenal functioning, includi
ng increased arginine vasopressin stores within corticotropin-releasing hor
mone (CRH) terminals in the external zone of the median eminence. Likewise,
we have previously shown that the proinflammatory cytokine, tumor necrosis
factor-alpha (TNF-alpha), provoked a time-dependent sensitization of neuro
endocrine and brain monoamine activity. To further explore the protracted c
onsequences of TNF-alpha, the present investigation determined whether the
cytokine sensitized activity of neuroendocrine regulatory brain regions, as
assessed by c-fos expression, and had protracted consequences on amygdaloi
d CRH, as well as hypothalamic corticotropin secretagogues. Indeed, immunor
eactivity for arginine vasopressin and corticotropin-releasing hormone, and
their colocalization within cell terminals of the median eminence, varied
over time following an initial 4.0-mug tumor necrosis factor-a treatment, p
eaking after 7 days and normalizing within 28 days. Within the central amyg
dala, a sensitization effect was evident as reflected by increased CRH immu
noreactivity, but this effect required re-exposure to the cytokine, unlike
the median eminence, changes that simply evolved with the passage of time.
As well, tumor necrosis factor-a provoked a marked sensitization of c-fos s
taining within the paraventricular nucleus of the hypothalamus, supraoptic
nucleus and the central amygdala.
From these data we suggest that tumor necrosis factor-alpha influences resp
onsivity of stressor-reactive brain regions and has protracted effects on c
entral neuropeptide expression within the hypothalamus and central amygdala
, although the time course for the effects vary across brain regions. Evide
ntly, exposure to tumor necrosis factor-a may promote neuroplasticity of br
ain circuits involved in mediating neuroendocrine, sickness or inflammatory
responses. It is suggested that such a sensitization may influence the res
ponse to immunological and traumatic insults and may thus be relevant to be
havioral pathology. (C) 2001 IBRO. Published by Elsevier Science Ltd. All r
ights reserved.