Wetmore L, Nance D M
Department of Physiology and Pathology, University of Manitoba, Winnipeg, Canada.
Exp Neurol. 1991 Aug;113(2):226-36. doi: 10.1016/0014-4886(91)90179-g.
The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats.
外侧隔区（LSA）与大鼠各种精神神经内分泌过程的调控有关。内分泌系统和免疫系统之间的相互作用以及免疫中的性别差异反映了免疫和神经内分泌系统的相互依存关系。外侧隔区的海人酸（KA）损伤不仅会改变神经内分泌过程，还会导致雌性大鼠体液免疫受到抑制。目前，我们评估了外侧隔区神经毒性损伤对雄性和雌性大鼠体液免疫反应及体重调节的影响。通过立体定位向成年雄性和雌性大鼠的外侧隔区注入0.25微升海人酸（1.5微克/微升）或0.5微升软骨藻酸（DA；0.3微克/微升）造成双侧损伤。在另一项研究中，仅对雌性大鼠使用0.25微升DA（0.6微克/微升）造成外侧隔区损伤。假手术包括向外侧隔区双侧注射0.9%的生理盐水。在用完全弗氏佐剂中的100微克卵清蛋白免疫后，检查这些损伤对抗体产生的影响。在免疫后的第7天和第14天采集血样。通过酶放大ELISA测定法测量抗卵清蛋白IgM和IgG抗体滴度。如先前发现的那样，成年雌性大鼠中海人酸诱导的外侧隔区损伤导致体重增加和体液免疫反应受到抑制。然而，神经毒素软骨藻酸造成的外侧隔区损伤对体重有类似影响，但对体液免疫没有影响。在雄性大鼠中，外侧隔区的海人酸或软骨藻酸损伤对体重调节和体液免疫反应均无影响。这些结果表明，外侧隔区神经毒性损伤对体重调节和体液免疫反应的影响具有性别特异性，进一步证明两种密切相关的海人酸盐神经毒素对体液免疫反应有不同影响，但对体重调节有类似影响。因此，雌性大鼠外侧隔区中参与体重抑制性控制的神经元对海人酸和软骨藻酸均敏感，而与免疫调节相关的外侧隔区神经元受海人酸和软骨藻酸的影响不同。更有趣的是，注意到软骨藻酸易感性存在性别差异，与雌性大鼠相比，雄性大鼠在注入软骨藻酸后外侧隔区的细胞损失更大。
