Bronzino J D, Austin La France R J, Morgane P J, Galler J R
Department of Engineering and Computer Science, Trinity College, Hartford, Connecticut 06106, USA.
Hippocampus. 1996;6(2):109-17. doi: 10.1002/(SICI)1098-1063(1996)6:2<109::AID-HIPO2>3.0.CO;2-K.
The ability of prenatally malnourished rats to establish and maintain long-term potentiation (LTP) of the perforant path/dentate granule cell synapse was examined in freely moving rats at 15, 30, and 90 days of age. Measures of the population EPSP slope and population spike amplitude (PSA) were calculated from dentate field potential recordings obtained prior to and at various times following tetanization of the perforant pathway. Significant enhancement of both population EPSP slope and PSA measures was obtained from all animals of both malnourished and well-nourished diet groups at 15 days of age. However, the magnitude of enhancement obtained from 15-day-old prenatally malnourished animals was significantly less than that of age-matched, well-nourished controls. At 30 days of age, PSA measures obtained from approximately 50% of prenatally malnourished 30-day-old rats showed no significant effect of tetanization, while measures obtained from the remaining 50% of these animals did not differ significantly from controls. EPSP slope measures for this age group followed much the same pattern, i.e., malnourished animals showing no significant enhancement of PSA measures exhibited only slight increases in EPSP slope beginning 1 h after tetanization and returned to baseline by 18 h post-tetanization. EPSP slope measures obtained from PSA-enhanced malnourished animals did not differ significantly from controls. At 90 days of age, PSA measures obtained from 50% of malnourished animals declined from pretetanization levels immediately following tetanization. Three hours after tetanization, however, this measure had increased to a level which did not differ significantly from that of the control group. PSA measures obtained from the remaining 50% of 90-day-old malnourished animals showed initial and sustained enhancement which did not differ significantly from those obtained from well-nourished age-matched controls. These results indicate that gestational protein malnutrition significantly affects the magnitude of tetanization-induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals) and significantly alters the time-course and magnitude of potentiation in approximately half of prenatally malnourished animals tested at 30 and 90 days of age. Given the primarily postnatal development of the dentate granule cells, these results may reflect malnutrition-induced delays in the neurogenesis and functional development of granule cells previously reported by our group. Most striking is the fact that significant impairments in LTP establishment were obtained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation commencing at birth is an intervention strategy incapable of ameliorating the effects of the gestational insult.
在15日龄、30日龄和90日龄的自由活动大鼠中，研究了产前营养不良大鼠建立和维持穿孔通路/齿状颗粒细胞突触长时程增强（LTP）的能力。从穿孔通路强直刺激之前及之后不同时间获得的齿状场电位记录中，计算群体兴奋性突触后电位（EPSP）斜率和群体峰电位幅度（PSA）。在15日龄时，营养不良组和营养良好组的所有动物的群体EPSP斜率和PSA测量值均有显著增强。然而，15日龄产前营养不良动物的增强幅度明显小于年龄匹配的营养良好对照组。在30日龄时，约50%的30日龄产前营养不良大鼠的PSA测量值显示强直刺激无显著影响，而其余50%动物的测量值与对照组无显著差异。该年龄组的EPSP斜率测量值呈现大致相同的模式，即PSA测量值无显著增强的营养不良动物，在强直刺激后1小时EPSP斜率仅略有增加，并在强直刺激后18小时恢复到基线水平。PSA增强的营养不良动物的EPSP斜率测量值与对照组无显著差异。在90日龄时，50%的营养不良动物的PSA测量值在强直刺激后立即从强直刺激前水平下降。然而，强直刺激后3小时，该测量值增加到与对照组无显著差异的水平。其余50%的90日龄营养不良动物的PSA测量值显示出初始和持续的增强，与年龄匹配的营养良好对照组无显著差异。这些结果表明，孕期蛋白质营养不良显著影响断奶前大鼠（15日龄动物）齿状颗粒细胞反应的强直刺激诱导增强幅度，并显著改变了约一半在30日龄和90日龄测试的产前营养不良动物的增强时程和幅度。鉴于齿状颗粒细胞主要在出生后发育，这些结果可能反映了我们小组先前报道的营养不良引起的颗粒细胞神经发生和功能发育延迟。最引人注目的是，90日龄的产前营养不良动物在LTP建立方面存在显著损伤，这意味着出生后开始的饮食康复是一种无法改善孕期损伤影响的干预策略。
