Fiacco Todd A, Rosene Douglas L, Galler Janina R, Blatt Gene J
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
J Comp Neurol. 2003 Feb 17;456(4):350-60. doi: 10.1002/cne.10531.
The postnatal development of excitatory amino acid receptor types including kainate, N-methyl-D-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was assessed in the hippocampus, entorhinal cortex, and adjacent neocortex in normal and prenatally protein malnourished rats ages 15, 30, 90, and 220 postnatal days by quantitative autoradiography. Tritiated ligands used to measure binding site density were (3)[H]kainate, (3)[H]MK-801, and (3)[H]AMPA, respectively. Kainate receptors showed statistically significant increases in binding density in stratum lucidum of CA3 (hippocampal mossy fiber zone) in 90- and 220-day-old malnourished rats compared with age- and sex-matched controls but not in 15- or 30-day-old malnourished rats. Compared with previous anatomic studies, these results are mostly in agreement with a significantly decreased hippocampal mossy fiber plexus in 15-, 90-, and 220-day-old rats but not in 30-day-old rats. These results suggested that the increased density of postsynaptic kainate receptors located mainly on proximal apical dendrites of CA3 pyramidal cells may be compensatory to decreased glutamate release due to the reduction in mossy fiber plexus. In contrast, the density of putative NMDA and AMPA receptors quantified in prenatally malnourished rats was comparable to the density quantified in age- and sex-matched control rats, as were all three receptor types in entorhinal cortex and adjacent neocortex. Thus, the selectivity of the compensation of (3)[H]kainate-labeled mossy fiber plexus in adult but not in early postnatal developing malnourished rats may help ensure continued breeding and survival of the species under otherwise adverse environmental conditions.
通过定量放射自显影技术,评估了正常及产前蛋白质营养不良大鼠在出生后15天、30天、90天和220天海马体、内嗅皮质及相邻新皮质中包括海人酸、N-甲基-D-天冬氨酸(NMDA)和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)在内的兴奋性氨基酸受体类型的产后发育情况。用于测量结合位点密度的氚化配体分别为(3)[H]海人酸、(3)[H]MK-801和(3)[H]AMPA。与年龄和性别匹配的对照组相比,90日龄和220日龄营养不良大鼠CA3区(海马苔藓纤维区)的透明层中海人酸受体结合密度有统计学显著增加,但15日龄或30日龄营养不良大鼠未见此现象。与先前的解剖学研究相比,这些结果大多与15日龄、90日龄和220日龄大鼠海马苔藓纤维丛显著减少一致,但30日龄大鼠未见此现象。这些结果表明,主要位于CA3锥体细胞近端顶树突上的突触后海人酸受体密度增加可能是对由于苔藓纤维丛减少导致的谷氨酸释放减少的一种代偿。相反,产前营养不良大鼠中推定的NMDA和AMPA受体密度与年龄和性别匹配的对照大鼠中测得的密度相当,内嗅皮质和相邻新皮质中的三种受体类型也是如此。因此,(3)[H]海人酸标记的苔藓纤维丛在成年但非出生后早期发育的营养不良大鼠中的代偿选择性,可能有助于确保该物种在其他不利环境条件下的持续繁殖和生存。