RECIPROCAL CHANGES IN EXPRESSION OF MESSENGER-RNA FOR NERVE GROWTH-FACTOR AND ITS RECEPTORS TRKA AND LNGFR IN BRAIN OF AGED RATS IN RELATION TO MAZE-LEARNING DEFICITS

Quantitative in situ hybridization was used to examine the expression of mRNA for nerve growth factor (NGF) and its receptors, p140Trk (TrkA ) and p75LNGFR (LNGFR), in different brain regions of adult (3-month-o ld) and aged (27-month-old) Wistar rats. The brain regions studied wer e hippocampus (dentate gyrus, CA3 region), basal forebrain (medial sep tum, diagonal band) and caudate-putamen. Prior to hybridization histoc hemistry behaviorally impaired as well as severely impaired animals we re selected from a large group of old rats according to their performa nce in the Morris water maze. The impaired rats showed longer escape l atencies and, thus, implicitly impaired performance in the place versi on of the task, but did not differ from adult controls on the platform crossing measure registered during the spatial probe trial. The sever ely impaired rats were significantly impaired on both measures, both i n comparison with the adult animals and in comparison with the impaire d aged rats. Inspection of the hippocampus revealed no age- or perform ance-related changes in NGF mRNA levels. The overall expression of Trk A mRNA in basal forebrain and caudate was found to be decreased in the impaired (-20%) as well as the severely impaired aged rats (-17%). A significant increase in p75LNGFR mRNA was found in the basal forebrain of the impaired rats in comparison with the severely impaired aged ra ts (+35%) and adult animals (+33%). These findings show that age-relat ed maze performance deficits are accompanied by a decrease in basal fo rebrain and striatal TrkA mRNA expression. The increase in basal foreb rain LNGFR mRNA levels observed in impaired, but not severely impaired , aged rats may reflect an early manifestation of processes underlying age-related cognitive deficits and may constitute a restorative and/o r compensatory mechanism, since these rats displayed fewer deficits in navigation of the maze.