Metabotropic glutamate receptor 5 (mGluR5)-mediated phosphoinositide hydrolysis and NMDA-potentiating effects are blunted in the striatum of aged rats: a possible additional mechanism in striatal senescence.
The aim of the present work was to verify whether an impairment of subtype 5 metabotropic glutamate receptor-mediated neurotransmission did occur in the aged striatum. To this end, the ability of the subtype 5 metabotropic glutamate receptor agonist, RS-2-chloro-5-hydroxyphenylglycine, to stimulate phosphoinositide hydrolysis and to potentiate N-methyl-d-aspartate-induced effects in striatal slices from young (3 months) and aged (24 months) rats was compared. The ability of RS-2-chloro-5-hydroxyphenylglycine to induce maximal phosphoinositide turnover and to potentiate N-methyl-d-aspartate effects was significantly reduced in slices from old vs. young rats. These changes were associated with a significant reduction in the expression of subtype 5 metabotropic glutamate receptor protein (-28.8%) and phospholipase C-beta1 (-55.8%) in old striata, while receptor messenger ribonucleic acid expression was unchanged. These results show that the signalling associated with subtype 5 metabotropic glutamate receptors undergoes significant age-related changes and that a reduced expression of subtype 5 metabotropic glutamate receptors and, more importantly, phospholipase C-beta1 may account for the functional decline of subtype 5 metabotropic glutamate receptors.
Domenici
Maria Rosaria
MR
Department of Pharmacology, Istituto Superiore di Sanità, Viale Regina Elena, 299 00161 Rome, Italy.
Pintor
Annita
A
Potenza
Rosa Luisa
RL
Gaudi
Simona
S
Grò
Maria Cristina
MC
Passarelli
Francesca
F
Reggio
Rosaria
R
Galluzzo
Mariangela
M
Massotti
Marino
M
Popoli
Patrizia
P
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006868:Hydrolysis; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009924:Organ Culture Techniques; D010716:Phosphatidylinositols / Q000378:metabolism; D054799:Phospholipase C beta; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
C578937:Grm5 protein, rat; D007527:Isoenzymes; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518035:Plcb1 protein, rat