Rykova V I, Leberfarb E Y, Stefanova N A, Shevelev O B, Dymshits G M, Kolosova N G
Institute of Cytology and Genetics, SB of RAS, 10 ul. Acad. Lavrentjeva, Novosibirsk 630090, Russia.
Adv Gerontol. 2011;24(2):234-43.
Proteoglycans (PG) are involved in the brain development as well as in the pathogenesis of age-related neurodegenerative disorders but underlying mechanism remains poorly understood. We showed that senescence-accelerated OXYS rats are suitable model of age-related cerebral dysfunctions. Here the content and composition of PG in the postnatal development and during behavioral decline were examined in the brain of OXYS and Wistar(control) rats at the ages of 1, 7, 14 days and 1, 2 and 14 months. Thereafter behavior in open field (OF) and elevated plus maze (EPM) was investigated. Data confirmed the absence of differences in the performance in tasks between Wistar and OXYS rats at the age of 1 month and showed faster age-related anxiety-like behavior decline in OXYS rats. The distribution of PG and the extent of their sulfation undergo dramatic and rapid changes in the brain during postnatal development both in Wistar and OXYS rats. Significant differences in these parameters appeared in the period of development of behavioral decline in OXYS rats. In contrast, no interstrain differences were revealed in the content and composition of PG in 14-month-old rats when behavior deteriorations are already developed. The results suggest that behavioral deterioration in OXYS rats occurs against the background of altered composition, quantity and glycosaminoglycans (GAG) sulfation.
蛋白聚糖(PG)参与大脑发育以及与年龄相关的神经退行性疾病的发病机制,但其潜在机制仍知之甚少。我们发现衰老加速的OXYS大鼠是与年龄相关的脑功能障碍的合适模型。在此,研究了OXYS大鼠和Wistar(对照)大鼠在出生后1天、7天、14天以及1个月、2个月和14个月时大脑中PG在出生后发育过程中和行为衰退期间的含量和组成。此后,研究了旷场试验(OF)和高架十字迷宫试验(EPM)中的行为。数据证实,1月龄时Wistar大鼠和OXYS大鼠在任务表现上没有差异,且显示OXYS大鼠与年龄相关的焦虑样行为衰退更快。在Wistar大鼠和OXYS大鼠出生后发育过程中,大脑中PG的分布及其硫酸化程度都发生了显著而快速的变化。在OXYS大鼠行为衰退期,这些参数出现了显著差异。相比之下,在行为衰退已经出现的14月龄大鼠中,未发现品系间PG含量和组成的差异。结果表明,OXYS大鼠的行为衰退是在PG组成、数量和糖胺聚糖(GAG)硫酸化改变的背景下发生的。