Guidi Sandra, Ciani Elisabetta, Severi Sabina, Contestabile Antonio, Bartesaghi Renata
Dipartimento di Fisiologia Umana e Generale, Università di Bologna, Bologna, Italy.
Hippocampus. 2005;15(3):285-301. doi: 10.1002/hipo.20050.
In all species examined, the dentate gyrus develops over an extended period that begins during gestation and continues up to adulthood. The aim of this study was to investigate the pattern of postnatal cell production in the dentate gyrus of the guinea pig, a rodent whose brain development has features more closely resembling the human condition than the most commonly used rodents (rat and mouse). Animals of different postnatal (P) ages received one or multiple injections of bromodeoxyuridine (BrdU), and the number of labeled cells in the dentate gyrus was counted after time intervals of 24 h or longer. The total granule cell number and the volume of the granule cell layer were evaluated in Nissl-stained brain sections from P1 and P30 animals. P1-P5 animals were treated with MK-801 to analyze the effect of NMDA receptor blockade on cell proliferation. Cell production occurred at a high rate (9,000-13,000 labeled cells 24 h after one injection) from P1 to P20, with a peak at 3-6 days of age, and then slowly declined from P20 to P30. The production of new cells continued in adult animals, although at a much-reduced rate (400 cells 24 h after one injection). About 20% of the labeled cells survived after a 17-day period and most (60%) of these cells had a neuronal phenotype. The total number of granule cells increased over the first postnatal month; in 30-day-old animals, it was 20% greater than in 1-day-old animals. Administration of MK-801 to P1-P5 animals caused an increase in cell proliferation restricted to the dorsal dentate gyrus. The present data show that, although the guinea pig dentate gyrus develops largely before birth, the production of new neurons continues at a high rate during the first postnatal month, leading to a considerable increase in cell number. This developmental pattern, resembling the human and nonhuman primate condition, may make the guinea pig a useful rodent model in developmental studies on dentate gyrus neurogenesis.
在所有被研究的物种中，齿状回在一个较长的时期内发育，这个时期始于妊娠期并持续至成年期。本研究的目的是调查豚鼠齿状回出生后细胞生成的模式，豚鼠作为一种啮齿动物，其大脑发育特征比最常用的啮齿动物（大鼠和小鼠）更接近人类情况。不同出生后（P）年龄的动物接受一次或多次溴脱氧尿苷（BrdU）注射，在24小时或更长的时间间隔后，对齿状回中标记细胞的数量进行计数。在出生后第1天（P1）和第30天（P30）动物的尼氏染色脑切片中评估颗粒细胞总数和颗粒细胞层的体积。对出生后第1天至第5天（P1 - P5）的动物用MK - 801进行处理，以分析NMDA受体阻断对细胞增殖的影响。从出生后第1天到第20天，细胞生成率很高（一次注射后24小时有9000 - 13000个标记细胞），在3 - 6日龄时达到峰值，然后从出生后第20天到第30天缓慢下降。成年动物中仍有新细胞生成，尽管速率大幅降低（一次注射后24小时有400个细胞）。约20%的标记细胞在17天的时间段后存活，其中大多数（60%）细胞具有神经元表型。颗粒细胞总数在出生后的第一个月内增加；在30日龄的动物中，比1日龄的动物多20%。对出生后第1天至第5天的动物给予MK - 801导致细胞增殖增加，且仅限于齿状回背侧。目前的数据表明，尽管豚鼠齿状回在很大程度上在出生前就已发育，但出生后第一个月内新神经元的生成仍以较高速率持续，导致细胞数量显著增加。这种发育模式类似于人类和非人类灵长类动物的情况，可能使豚鼠成为齿状回神经发生发育研究中一种有用的啮齿动物模型。
