Rapoport Stanley I, Schapiro Mark B, May Conrad
Section on Brain Physiology and Metabolism, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Arch Neurol. 2004 Nov;61(11):1721-4. doi: 10.1001/archneur.61.11.1721.
Markers of human brain dopamine metabolism are reported to decline with age. However, the cerebrospinal fluid (CSF) concentration of homovanillic acid (HVA), a major dopamine metabolite, is reported to not change or to increase in elderly individuals.
To estimate the rate of delivery of HVA from the brain to CSF, taking into account the HVA concentration gradient in the spinal subarachnoid space and CSF flow.
Homovanillic acid concentrations were measured in 5 serial 6-mL aliquots of CSF removed from the L3-4 or L4-5 interspaces of 7 healthy young (mean +/- SD age, 28.7 +/- 4.6 years) subjects and 7 healthy elderly (mean +/- SD age, 77.1 +/- 6.3 years) subjects. Cisterna magna HVA concentrations were estimated from the slopes of the HVA concentrations along the spinal subarachnoid space. The products of cisternal HVA concentrations and published values for CSF flow were used to estimate lower limits for brain delivery of HVA to CSF, according to the Fick principle.
The mean +/- SD HVA concentration in the initial lumbar CSF sample in the young subjects, 116 +/- 66 pmol/mL, did not differ significantly from 140 +/- 86 pmol/mL in the elderly subjects. Estimated cisternal HVA concentrations equaled 704 and 640 pmol/mL, respectively, in the young and elderly subjects. Multiplying these concentrations by CSF flow rates of 591 and 294 mL/d, respectively, gave lower limits for rates of delivery of HVA from the brain to CSF. These rates equaled 416 and 175 nmol/d, respectively.
A 50% decline in the lower limit for the rate of HVA delivery from the brain to CSF in elderly individuals is consistent with other evidence that brain dopaminergic neurotransmission declines with age.
据报道，人类脑多巴胺代谢标志物会随着年龄增长而下降。然而，据报道，主要多巴胺代谢产物高香草酸（HVA）的脑脊液（CSF）浓度在老年人中并未改变或有所升高。
考虑到脊髓蛛网膜下腔的HVA浓度梯度和脑脊液流动情况，估算HVA从脑向脑脊液的输送速率。
从7名健康年轻（平均±标准差年龄，28.7±4.6岁）受试者和7名健康老年（平均±标准差年龄，77.1±6.3岁）受试者的L3 - 4或L4 - 5椎间隙采集5份连续6 mL的脑脊液样本，测量其中HVA的浓度。根据沿着脊髓蛛网膜下腔的HVA浓度斜率估算枕大池HVA浓度。根据菲克原理，将枕大池HVA浓度与已发表的脑脊液流动值相乘，以估算HVA从脑向脑脊液输送的下限速率。
年轻受试者初始腰段脑脊液样本中HVA的平均±标准差浓度为116±66 pmol/mL，与老年受试者的140±86 pmol/mL无显著差异。年轻和老年受试者的估算枕大池HVA浓度分别为704和640 pmol/mL。将这些浓度分别乘以591和294 mL/d的脑脊液流速，得出HVA从脑向脑脊液输送速率的下限。这些速率分别为416和175 nmol/d。
老年人中HVA从脑向脑脊液输送速率下限下降50%，与脑多巴胺能神经传递随年龄下降的其他证据一致。
