DIFFERENTIAL AND SEX-SPECIFIC EFFECTS OF KAINIC ACID AND DOMOIC ACID LESIONS IN THE LATERAL SEPTAL AREA OF RATS ON IMMUNE FUNCTION AND BODY-WEIGHT REGULATION

DIFFERENTIAL AND SEX-SPECIFIC EFFECTS OF KAINIC ACID AND DOMOIC ACID LESIONS IN THE LATERAL SEPTAL AREA OF RATS ON IMMUNE FUNCTION AND BODY-WEIGHT REGULATION
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DOI:
10.1016/0014-4886(91)90179-g
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发表时间:
1991-08-01
影响因子:
5.3
通讯作者:
NANCE, DM
NANCE, DM
中科院分区:
医学2区
文献类型:
--
作者:
WETMORE, L;NANCE, DM

文献摘要

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大鼠外侧隔区(LSA)参与了多种精神神经内分泌过程的控制。内分泌和免疫系统之间的相互作用以及免疫的性别差异反映了免疫和神经内分泌系统的相互依赖性。海人酸(KA)损伤外侧隔区不仅改变神经内分泌过程,而且产生抑制体液免疫在雌性大鼠。目前,我们已经评估了LSA神经毒性损伤对雄性和雌性大鼠体液免疫应答和体重调节的影响。通过立体定向将0.25 μl红藻氨酸(1.5 μg/μl)或0.5 μl软骨藻酸(DA; 0.3 μg/μl)注入成年雄性和雌性大鼠的LSA中,造成双侧LSA损伤。在另一项研究中,仅在雌性大鼠中使用0.25 μl DA(0.6 μg/μl)产生LSA损伤。假手术包括向LSA中双侧注射0.9%盐水。在用100 μg卵清蛋白的完全弗氏佐剂免疫后,检查这些病变对抗体产生的影响。在免疫后第7天和第14天收集血液样品。抗卵清蛋白IgM和IgG抗体滴度通过酶放大ELISA测定来测量。如前所述,KA诱导的成年雌性大鼠LSA病变导致体重增加和体液免疫应答抑制。然而,用神经毒素DA产生的LSA病变对体重有类似的影响,但对体液免疫没有影响。在雄性大鼠中,无论是体重调节,也不是体液免疫反应的影响KA或DA病变的LSA。这些结果表明,神经毒性LSA病变对体重调节和体液免疫反应的影响是性别特异性的,并进一步表明,两个密切相关的红藻氨酸神经毒素对体液免疫反应有不同的影响,但对体重调节有相似的影响。因此,在LSA中的神经元,参与抑制控制体重的雌性大鼠是敏感的KA和DS,而在LSA中的神经元与免疫调节的差异KA和DA的影响。进一步的兴趣,DA的敏感性的性别差异,注意到,与雄性大鼠表现出更大的细胞损失的LSA DA输注后,与雌性大鼠相比。
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 μl of kainic acid (1.5 μg/μl) or 0.5 μl of domoic acid (DA; 0.3 μg/μl) into the LSA. In an additional study, LSA lesions using 0.25 μl of DA (0.6 μg/μl) 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 μg 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 DS, 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.