AGE-RELATED-CHANGES IN THE RELATIVE ABUNDANCE OF NMDAR1 MESSENGER-RNASPLICED VARIANTS IN THE RAT-BRAIN

WE have investigated the age-dependent profile of two groups of NMDAR1 mRNA isoforms, the NR1(0XX) and the NR1(1XX), which are characterized by the absence and the presence, respectively, of an N-terminal posit ioned 21 amino acid insert. mRNAs of the two spliced variants were inv estigated at different ages in discrete rat brain areas by means of th e reverse transcription-polymerase chain reaction. The existence of re gional variations was confirmed as well as a region-specific pattern o f NR1(0XX/1XX) ratio and its age-dependent changes. At 6 months, the r atio was >3 in prosencephalic structures and <1 in metencephalic regio ns. The greatest age-related changes were found in the cerebellum that switched from a maximal ratio of 5.1 +/- 0.4 at day 6 through a progr essive decay down to the value of 0.3 +/- 0.04 at 24 months. Age-depen dent changes of the different NR1 spliced variant mRNAs are relevant t o understand possible regulatory mechanisms of the pharmacological pro perties and functions of different NMDAR subtypes.