Developmental maturation of the N‐methyl‐d‐aspartic acid receptor channel complex in postnatal rat brain

Abstract

The N-methyl-D-aspartate (NMDA) receptor plays an important role in developmental plasticity. Previous studies have reported differences between the NMDA receptor-channel complex in the rat pup brain and the adult brain. In the present study, modulation of the NMDA channel complex as a function of age was measured to determine when the temporal switching of the NMDA receptor from the immature form to the adult mature form takes place. [(3)H]MK-801 binding was measured in the rat forebrain from postnatal day 1 to day 21. Our data suggest the presence of two types of NMDA receptors - an immature type and a mature type. The immature NMDA receptor, seen during the early postnatal period (day 1-day 14) is highly sensitive to spermidine, L-glutamate alone potentiates [(3)H]MK-801 binding, and glycine failed to potentiate an L-glutamate-induced increase in [(3)H]MK-801 binding. During the late postnatal period (after day 14) spermidine alone did not increase [(3)H]MK-801 binding as potently as it did during the early postnatal period, high-affinity [(3)H]MK-801 binding was not seen in the presence of L-glutamate alone, and L-glutamate and glycine or L-glutamate and spermidine or L-glutamate, glycine and spermidine together, significantly increased [(3)H]MK-801 binding in a manner similar to that reported in the adult brain. Together, the pharmacology of the NMDA receptor during the early postnatal period differs from the adult-like receptor seen during the late postnatal period, and that in rats the apparent switching of the NMDA receptor from the immature type to the mature type takes place after the second postnatal week.

Attenuation of Acute Morphine Withdrawal in the Neonatal Rat by the Competitive NMDA Receptor Antagonist LY235959

“…The accumulating evidence indicates that the various subunits (NR1, NR2A-D, NR3A) composing the native NMDA receptor channel undergo dramatic differential change during the first few weeks of the postnatal life in the rat (Dingledine et al 1999). It has been suggested that the NMDA receptor is not present in fully mature form until the second postnatal week in the rat (Sircar 2000). Thus, the pharmacological effects of NMDA antagonism in the infant may not necessarily be comparable to those in the adult.…”

Mechanisms of Toxicity in Huntington’s Disease and the Role of Polyamines in NMDAR-Mediated Excitotoxicity: Review

“…89 Neonatal sıçanlarda poliamin biyosentezinin durdurulmasının, erişkinlik evresinde özellikle serebellumda nöronal kayıplara neden olduğu belirlenmiştir. 90,91 Poliaminlerin sinir sisteminde bu tip önemli bir etkide bulunmalarının temelinde NMDAR ile etkileşimleri olduğu düşünülmektedir. Gelişim evresinde MSS'de poliamin miktarının en yüksek seviyesinde olduğu ve gelişim tamamlandı-ğında miktarının azaldığı tespit edilmiştir.…”

“…Gelişim evresinde MSS'de poliamin miktarının en yüksek seviyesinde olduğu ve gelişim tamamlandı-ğında miktarının azaldığı tespit edilmiştir. 91 Gelişim döneminde NMDAR'nin de nöronal büyüme, hücre göçü ve sinaps oluşumunda etkili olması, poliaminlerin, NMDAR'yi düzenleyici işleve sahip olabileceklerini düşündürmektedir. 92 …”

The Effect of N-Methyl-D-Aspartate (NMDA) Receptor Blockade and Physical Environmental Enrichment During Childhood on Emotional and Cognitive Function in Adulthood in Balb/C Mice

“…Çalışmamızda NMDA reseptör blokajı yaptığımız gelişim penceresi, NMDA reseptörlerinin tamamen olgun şekle dönüştüğü zaman dilimini kapsamaktadır (41). NMDA reseptör blokajının sinaps oluşumunun yoğun olduğu yeni doğan döneminde apopitoza bağlı nörodejenerasyona, yeni doğandanvpuberteye geçiş aşamasında minimal nörodejenerasyona ve puberteden sonra yetişkin dönem-de ise eksitotoksik nörodejenerasyona neden olduğu gösterilmiştir (42)(43)(44).…”