Relationship of APP mRNA transcripts and levels of NGF and low-affinity NGF receptors to behavioral measures of age-related cognitive dysfunction.
This study was designed to examine the relationship between cognitive function and endogenous levels of NGF, low-affinity NGF receptor (LNGFR), and amyloid precursor protein (APP) mRNAs. Using 3 month (n = 5), 18 month (n = 40), and 29 month (n = 17) Fischer-344 male rats, cognitive function was assessed with the Morris water maze, reverse transcription and polymerase chain reaction were used to quantify APP mRNAs, and NGF and LNGFR levels were determined with an ELISA. Cognitive function declined progressively with age from 3 months to 18 months, and from 18 months to 29 months, but only RNA content in the tissue declined significantly from 3 months to 18 months. Between 18 month and 29 month rats were small but statistically significant decreases only for Kunitz protease inhibitor (KPI)-inclusive mRNAs and cortical NGF levels. There was a small but statistically significant correlation between cognitive function and %KPI (the amount of KPI APP mRNAs relative to the total amount of APP mRNA), with lower %KPI related to more impaired spatial learning. No other statistically significant correlation or linear relationship could be detected between cognitive function and any of the other neurological measures or any combination of these measures (i.e., hippocampal levels of APP 695 mRNA, cortical and hippocampal levels of NGF, and cortical, hippocampal, and basal forebrain levels of LNGFR).(ABSTRACT TRUNCATED AT 250 WORDS)
Lindner
M D
MD
University of Rochester School of Medicine, Monroe Community Hospital, New York 14620.
Dworetzky
S I
SI
Sampson
C
C
Loy
R
R
D000375:Aging / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007858:Learning; D008297:Male; D008568:Memory / Q000502:physiology; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D016548:Prosencephalon / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D014158:Transcription, Genetic
D016564:Amyloid beta-Protein Precursor; D017931:DNA Primers; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor