Rtpcr

Hypothalamus

pg/mg pg/ml

Hypothalamus

pg/mg pg/ml

0 2 4 6 hr □ Hypcfrdansfl Raara

Figure 3. Systemic administration of LPS induces the expression of IL-ip and IL-lra in the brain of mice. Mice were injected intraperitoneally with LPS (lOpg/mouse) and killed just before or at different times after injection. Total RNA was extracted from the hypothalamus and submitted to RT-PCR to determine transcripts for IL-lp and IL-lra, using beta2-microg!obulin (P2mgl) as an internal standard. Levels of IL-lfS were measured in the hypothalamus (pg/mg protein) and plasma (pg/ml) using a validated ELISA (mean of 5 different experiments).

Figure 4. Vagotomy attenuates the depressing effects of systemic IL-ip on social exploration of a juvenile conspecific introduced into the home cage of the test animal. The experiment was carried out on rats that had been submitted to vagotomy (VOX) or sham surgery (sham) 4 weeks before the test. Solvent or recombinant rat IL-ip (15|ig/rat) was injected ip immediately after the first behavioral session that took place at time 0 (baseline) and the same animals were tested again with different juveniles 2, 4, and 6h later (n = 5 for each experimental group). Duration of exploration was expressed as percentage of baseline (81 to lOOsec for 4min of test) (From Bluthe et al., 1996b).

Figure 4. Vagotomy attenuates the depressing effects of systemic IL-ip on social exploration of a juvenile conspecific introduced into the home cage of the test animal. The experiment was carried out on rats that had been submitted to vagotomy (VOX) or sham surgery (sham) 4 weeks before the test. Solvent or recombinant rat IL-ip (15|ig/rat) was injected ip immediately after the first behavioral session that took place at time 0 (baseline) and the same animals were tested again with different juveniles 2, 4, and 6h later (n = 5 for each experimental group). Duration of exploration was expressed as percentage of baseline (81 to lOOsec for 4min of test) (From Bluthe et al., 1996b).

abdominal cavity and sensed by afferent vagal terminals since vagotomy did not block sickness behaviour induced by subcutaneous and intravenous injections of IL-lp (Bluthe, Michaud, Kelley, & Dantzer, 1996a), and had no effect on sickness behaviour induced by central injection of IL-lp (Fig. 5) (Bluthe, Michaud, Kelley, & Dantzer, 1996b).

According to the hypothesis of a neural transmission pathway of immune signals from the periphery to the brain, section of vagal afferents should abrogate the induction of brain cytokines expression in response to intraperitoneal administration of LPS and IL-ip. In accordance with this prediction, vagotomy was demonstrated to abrogate LPS- and IL-ip-induced increases in IL-ip mRNA in the hypothalamus and

Figure 5. Vagotomy does not block the depressing effect of icv IL-lß on social exploration. Solvent or recombinant rat IL-lß (45ng/rat) was injected icv immediately after the first behavioral session that took place at time 0 (baseline). Same conventions as in Fig. 4 (n = 5 for each experimental group). Baseline values varied from 96 to 127sec for 4min of test). From Bluthe et al., 1996b).

Figure 5. Vagotomy does not block the depressing effect of icv IL-lß on social exploration. Solvent or recombinant rat IL-lß (45ng/rat) was injected icv immediately after the first behavioral session that took place at time 0 (baseline). Same conventions as in Fig. 4 (n = 5 for each experimental group). Baseline values varied from 96 to 127sec for 4min of test). From Bluthe et al., 1996b).

hippocampus but not in the pituitary (Layé et al., 1995; Hansen, Taishi, Chen, & Krueger, 1998).

The brain actions of peripheral cytokines that are mediated by neural afferents also include fever and activation of the HPA axis since vagotomy attenuates LPS-induced fever and increase in plasma ACTH levels (Watkins, Maier, & Goehler, 1995).

All of these data converge to support the hypothesis that vagal afferents transmit the immune message from the abdominal cavity to the brain. Whether other neural afferents are involved in the transmission of the immune message originating from other bodily sites to the brain and whether the circumventricular organs are also involved in the relatively rare case in which cytokine levels dramatically increase in the general circulation remain to be determined.

Defeat Depression

Defeat Depression

Learning About How To Defeat Depression Can Have Amazing Benefits For Your Life And Success! Discover ways to cope with depression and melancholic tendencies! Depression and anxiety particularly have become so prevalent that it’s exceedingly common for individuals to be taking medication for one or even both of these mood disorders.

Get My Free Ebook


Post a comment