Grachev I D, Swarnkar A, Szeverenyi N M, Ramachandran T S, Apkarian A V
Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
J Neurochem. 2001 Apr;77(1):292-303. doi: 10.1046/j.1471-4159.2001.t01-1-00238.x.
In our most recent study of normal aging, we found decreased concentration of multiple chemicals in the brain of middle-aged subjects, as compared with younger subjects using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). We hypothesized that these age-dependent differences in brain chemistry changes might be a reflection of the multichemical-networking-profile (MCNP) changes during aging. Using (1)H-MRS and correlation analysis, we examined the patterns of regional chemical levels and MCNP within and across multiple brain regions for all nine chemicals of (1)H-MR spectra. The brain chemistry changes and MCNP patterns were compared between 21 young (19--31-year-old) and 31 middle-aged (40--52-year-old) normal volunteers. Middle-aged subjects demonstrated a significant decrease of chemical levels in the prefrontal cortex and sensorimotor cortex (SMC), as compared with the young age group. Of these, neurotransmitters GABA and glutamate in the dorsolateral prefrontal cortex (DLPFC) were altered the most. We also found a significant increase of overall chemical correlation strength in MCNP within and across all studied brain regions with increased age. These changes were caused by alterations in the pattern of negative chemical connectivity across brain regions, which become weaker (less negative) in middle-aged subjects. The interregional chemical connectivity for the cingulate cortex, SMC and the thalamus was changed the most with increased age. Increased levels of chemical correlation strength across brain regions in aging were found for most chemicals studied (including neurotransmitters GABA and glutamate), and not for N-acetyl aspartate. These age-related differences in the connectivity of neurotransmitters were not region dependent. The results suggest that aging is associated with changes of the regional brain chemistry and the brain MCNP. The latter process may reflect an adaptive or compensatory response (possibly related to the elongation of dendrites with aging) to reduced levels of regional brain chemicals. The (1)H-MRS approach proposed here can be used as a valuable tool in the study of the brain chemistry, MCNP and their relationships in normal and abnormal aging.
在我们最近一项关于正常衰老的研究中，与使用体内质子磁共振波谱（(1)H-MRS）的年轻受试者相比，我们发现中年受试者大脑中多种化学物质的浓度降低。我们推测，大脑化学变化中这些与年龄相关的差异可能反映了衰老过程中多化学物质网络图谱（MCNP）的变化。使用(1)H-MRS和相关分析，我们检查了(1)H-MR谱中所有九种化学物质在多个脑区内部和之间的区域化学水平和MCNP模式。对21名年轻（19 - 31岁）和31名中年（40 - 52岁）正常志愿者的大脑化学变化和MCNP模式进行了比较。与年轻组相比，中年受试者前额叶皮质和感觉运动皮质（SMC）中的化学物质水平显著降低。其中，背外侧前额叶皮质（DLPFC）中的神经递质γ-氨基丁酸（GABA）和谷氨酸变化最为明显。我们还发现，随着年龄增长，所有研究脑区内部和之间的MCNP中总体化学相关强度显著增加。这些变化是由脑区之间负性化学连接模式的改变引起的，中年受试者的这种连接模式变得更弱（负性更小）。随着年龄增长，扣带回皮质、SMC和丘脑的区域间化学连接变化最大。在大多数研究的化学物质（包括神经递质GABA和谷氨酸）中，发现衰老过程中脑区之间化学相关强度增加，而N-乙酰天门冬氨酸则不然。神经递质连接性的这些与年龄相关的差异并不依赖于脑区。结果表明，衰老与区域脑化学和大脑MCNP的变化有关。后一过程可能反映了对区域脑化学物质水平降低的适应性或补偿性反应（可能与衰老过程中树突的延长有关）。这里提出的(1)H-MRS方法可作为研究正常和异常衰老过程中脑化学、MCNP及其关系的有价值工具。
