Mascarucci P, Perego C, Terrazzino S, De Simoni M G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Neuroscience. 1998 Oct;86(4):1285-90. doi: 10.1016/s0306-4522(98)00105-5.
The involvement of vagal afferents in the communication pathway from the immune system to the brain was studied. Glutamate was measured in the nucleus tractus solitarius, the brain area receiving glutamatergic vagal afferents, after peripheral injection of lipopolysaccharide or interleukin-1 beta. Intraperitoneal or intravenous saline or intraperitoneal heat-inactivated interleukin-1 beta increased glutamate release, measured by brain microdialysis in freely-moving rats at 20 min (137 +/- 19%, 126 +/- 10% and 133 +/- 6%, respectively), without inducing any other change up to 3 h after injection. Intraperitoneal lipopolysaccharide (10 micrograms/rat) increased glutamate at 20 min (132 +/- 10%) and at 60 min (208 +/- 26%). To compare lipopolysaccharide effectiveness by the two routes, serum levels of interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha were measured. Intravenous lipopolysaccharide induced each cytokine more rapidly and efficiently than intraperitoneal lipopolysaccharide. Perfusion with tetrodotoxin (1 microM) in the dialysis probe decreased glutamate basal levels by approximately 20% and completely prevented lipopolysaccharide effects, showing the neuronal component of the glutamate measured. Except for the 20-min increase, intravenous lipopolysaccharide (10 micrograms/rat) did not affect glutamate release. Intraperitoneal interleukin-1 beta (4 micrograms/rat) increased glutamate release at 20 min (126 +/- 6%) and at 40 min (150 +/- 18%). These data indicate that vagal glutamatergic system in the nucleus tractus solitarius is activated by intraperitoneal injections of immunoactive compounds.
研究了迷走神经传入纤维在从免疫系统到大脑的通信通路中的作用。在腹腔注射脂多糖或白细胞介素-1β后，测量孤束核（接受谷氨酸能迷走神经传入纤维的脑区）中的谷氨酸水平。腹腔内或静脉内注射生理盐水或腹腔内注射热灭活的白细胞介素-1β可增加谷氨酸释放，在自由活动的大鼠中通过脑微透析在20分钟时测量（分别为137±19%、126±10%和133±6%），注射后3小时内未引起任何其他变化。腹腔注射脂多糖（10微克/只大鼠）在20分钟时（132±10%）和60分钟时（208±26%）增加谷氨酸水平。为比较两种途径注射脂多糖的效果，测量了白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α的血清水平。静脉注射脂多糖比腹腔注射脂多糖更迅速、有效地诱导每种细胞因子。在透析探针中灌注河豚毒素（1微摩尔）可使谷氨酸基础水平降低约20%，并完全阻止脂多糖的作用，表明所测量的谷氨酸具有神经元成分。除了20分钟时的增加外，静脉注射脂多糖（10微克/只大鼠）不影响谷氨酸释放。腹腔注射白细胞介素-1β（4微克/只大鼠）在20分钟时（126±6%）和40分钟时（150±18%）增加谷氨酸释放。这些数据表明，腹腔注射免疫活性化合物可激活孤束核中的迷走神经谷氨酸能系统。
