Heyes M P, Gravell M, London W T, Eckhaus M, Vickers J H, Yergey J A, April M, Blackmore D, Markey S P
Section on Analytical Biochemistry, NIMH, Bethesda, MD 20892.
Brain Res. 1990 Oct 29;531(1-2):148-58. doi: 10.1016/0006-8993(90)90768-7.
Sustained increases in CSF concentrations of the excitotoxin quinolinic acid (QUIN) occur in patients with AIDS and have been implicated in the pathogenesis of the AIDS dementia complex. Macaques in captivity may also develop immunodeficiency syndromes caused by retrovirus infection, including simian retrovirus type-D. In the present study, CSF QUIN concentrations were moderately increased in retrovirus type-D-positive/antibody-negative macaques (163.8 +/- 35.1 nmol/l; P less than 0.0001, n = 21) but not virus-negative/antibody-positive macaques (27.4 +/- 9.4 nmol/l, n = 8) compared to uninfected control macaques (23.0 +/- 1.6 nmol/l; n = 22). CSF QUIN concentrations in virus-positive/antibody-negative macaques tended to remain elevated over a 4-20 month period. Post-mortem studies of 9 virus-positive/antibody-negative macaques and 6 virus-negative/antibody-positive macaques revealed inflammatory responses in the brains of 6 of 9 virus-positive/antibody negative macaques, including lymphocytic infiltrates of the choroid plexus in 3 macaques, glial nodules in 3 macaques and perivascular infiltrates in 1 macaque. These lesions were not extensive and no evidence of brain atrophy was observed. No lesions were observed in the 6 antibody-positive/virus-negative macaques. Small increases in plasma L-kynurenine in virus-positive/antibody-negative macaques are consistent with activation of indoleamine-2,3-dioxygenase, the first enzyme in the kynurenine pathway. We conclude that sustained moderate increases in CSF QUIN occur in viremic simian retrovirus type-D macaques. The increases in CSF QUIN may reflect inflammatory responses within the brain or synthesis of QUIN precursors in systemic tissues, their entry into brain and subsequent conversion to QUIN. The neuropathologic significance of these increases in CSF QUIN remains to be determined.
艾滋病患者脑脊液中兴奋性毒素喹啉酸（QUIN）浓度持续升高，这与艾滋病痴呆综合征的发病机制有关。圈养猕猴也可能因逆转录病毒感染而患上免疫缺陷综合征，包括D型猿猴逆转录病毒感染。在本研究中，与未感染的对照猕猴（23.0±1.6 nmol/l；n = 22）相比，D型逆转录病毒阳性/抗体阴性的猕猴脑脊液中QUIN浓度中度升高（163.8±35.1 nmol/l；P＜0.0001，n = 21），而病毒阴性/抗体阳性的猕猴（27.4±9.4 nmol/l，n = 8）则未升高。病毒阳性/抗体阴性的猕猴脑脊液中QUIN浓度在4至20个月期间往往持续升高。对9只病毒阳性/抗体阴性猕猴和6只病毒阴性/抗体阳性猕猴进行的尸检研究显示，9只病毒阳性/抗体阴性猕猴中有6只大脑出现炎症反应，包括3只猕猴脉络丛淋巴细胞浸润、3只猕猴神经胶质结节和1只猕猴血管周围浸润。这些病变并不广泛，未观察到脑萎缩迹象。6只抗体阳性/病毒阴性猕猴未观察到病变。病毒阳性/抗体阴性猕猴血浆中L-犬尿氨酸略有升高，这与犬尿氨酸途径中的第一种酶吲哚胺-2,3-双加氧酶的激活一致。我们得出结论，感染猿猴D型逆转录病毒血症的猕猴脑脊液中QUIN持续中度升高。脑脊液中QUIN的升高可能反映了大脑内的炎症反应或全身组织中QUIN前体的合成、它们进入大脑并随后转化为QUIN。脑脊液中QUIN升高的神经病理学意义尚待确定。
