Aging associated changes in serotoninergic and dopaminergic pre- and postsynaptic neurochemical markers in the rat brain.
Measurements of endogenous levels of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC), and biochemical and autoradiographic investigations on 5-HT and DA receptors were made in various brain regions in male rats at three different ages: 3 months, 10 months and 22 months. Age-dependent decreases in 5-HT levels associated with parallel increases in 5-HIAA/5-HT ratio were observed in the hypothalamus, striatum, hippocampus and cerebral cortex, suggesting an accelerated 5-HT turnover in aged rats. Similarly, DA levels were lower, and DOPAC/DA ratio was higher in the striatum of 22-month-old compared to 3-month-old or 10-month-old rats. Of the three different classes of 5-HT receptors which were examined, 5-HT1B sites exhibited the largest age-dependent decrease in density, followed by 5-HT2 sites, while 5-HT1A sites remained practically unchanged during aging. By comparison, the loss of striatal D2 receptors in 22-month-old rats compared to young adults was much greater than that of any 5-HT receptor subtype. Such differential age-dependent alterations of the various classes of 5-HT receptors and of dopaminergic versus serotoninergic synaptic markers might be responsible for at least some of the functional deficits in aged animals.
Gozlan
H
H
INSERM U288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médicine Pitié-Salpêtrière, Paris, France.
Daval
G
G
Verge
D
D
Spampinato
U
U
Fattaccini
C M
CM
Gallissot
M C
MC
el Mestikawy
S
S
Hamon
M
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D015415:Biomarkers; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin; D004298:Dopamine