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NGF levels in the CNS of aged- rats following a subacute treatment with levocarnitine acetyl (ALCAR)
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Pharmacological Research, Vol. 26, Supplement 1, 1992
NGFLEVBLSINTHECNSOFAGEDRATSFOLLOWINGASLJBACUIETREATMENT WITHLEVOCARNITIh%ACETYL(ALCAR) Domitilla Navarra, Giulio Taglialatela, Roberto Cruciani, Maria Teresa Ramacci, Lueiano Angelucci* Institute for Research on Senescence,Sigma Tau, Pomezia, & *Farmacologia II, University of Rome, Rome, Italy We have previously shown that chronic treatment with ALCAR in old rats prevents some agerelated CNS impairments, which may be due to reduced neurotrophic support to neurons. Also, ALCAR potentiates NGF action in PC12 cells and prevents the reduction of NGF receptors in the aged rat CNS. Based on these findings, we have studied the effect of a subacute treatment with ALCAR (200 mg/kg ip for 8 days) on the NGF levels in the CNS of adult and aged rats. A significant increase of NGF levels in the hippocampus and basal forebrain of aged rats was observed following treatment with ALCAR, while no changes were found in the same CNS areas of ALCAR-treated adult animals. The NGF levels in frontal cortex and cerebellum were not affected by ALCAR in either adult or aged rats. No significant differences in CNS NGF content were observed between adult and aged untreated animals. These data suggest a strategy, of possible therapeutical importance, to increase NGF content in those CNS areas that are impaired in aged subjects, especially in the light of previous findings showing that a subacute i.c.v. treatment with NGF rescues atrophic cholinergic neurons of the basal forebrain and septum in aged rats ‘I. * Fischer et al., Nature 329: 65-68; 1987
CORTICO-STRIATAL GLUTAMATERGIC PATHWAYS MODULATION OF STRIATAL DOPANINE TURNOVER, ASCORBIC ACID CATABOLISM AND BEHAVIOR IN THE RAT P.Enrico, M .S.Desole, M . Niele, L.Fresu, G.Esposito, G. De of Pharmacology - Sassari Natale and E. M iele - Institute Levels of DA,DOPAC,ascorbic acid(M) and dehydroascorbic acid (DHAA) were determined by HPLC in the synaptosomal fraction and whole striatum of rats,whose fronto-parietal cortex had been bilaterally ablated,after a single apomorphine (AP0,l.O mg/kg sc),scopolamine (SCOP, 0,6 mg/kg SC) or d-amphetamine (AMPH, 2.0 mg/kg ip) injection,following a recovery period of 21 days.APO,SCOP and ANPH significantly increased the DHAA/AA ratio in the whole striatum of unoperated and sham operated rats,but failed to increase it in ablated rats.The synapto= somal DHAA/AA ratio was actually decreased in all groups.APO,SCOP and ANPH decreased the DOPAC/DA ratio in the whole striatum of all groups-Cortical ablation potentiated the AMPH-induced and attenuated the SCOP-induced motor hyperactivity.We conclude that APO-,SCOP- and ANPH-induced increase in striatal AA oxidation requires integrity of the cortico-striatal glutamatergic pathways. Furthermore,AA oxidation occurs in the extracellular space. Cortico-striatal glutamatergic pathways modulate both striatal dopaminergic system activity and behavior.Supported by MURST 60%
Pharmacological Research, Vol. 26, Supplement 1, 1992
NGFLEVBLSINTHECNSOFAGEDRATSFOLLOWINGASLJBACUIETREATMENT WITHLEVOCARNITIh%ACETYL(ALCAR) Domitilla Navarra, Giulio Taglialatela, Roberto Cruciani, Maria Teresa Ramacci, Lueiano Angelucci* Institute for Research on Senescence,Sigma Tau, Pomezia, & *Farmacologia II, University of Rome, Rome, Italy We have previously shown that chronic treatment with ALCAR in old rats prevents some agerelated CNS impairments, which may be due to reduced neurotrophic support to neurons. Also, ALCAR potentiates NGF action in PC12 cells and prevents the reduction of NGF receptors in the aged rat CNS. Based on these findings, we have studied the effect of a subacute treatment with ALCAR (200 mg/kg ip for 8 days) on the NGF levels in the CNS of adult and aged rats. A significant increase of NGF levels in the hippocampus and basal forebrain of aged rats was observed following treatment with ALCAR, while no changes were found in the same CNS areas of ALCAR-treated adult animals. The NGF levels in frontal cortex and cerebellum were not affected by ALCAR in either adult or aged rats. No significant differences in CNS NGF content were observed between adult and aged untreated animals. These data suggest a strategy, of possible therapeutical importance, to increase NGF content in those CNS areas that are impaired in aged subjects, especially in the light of previous findings showing that a subacute i.c.v. treatment with NGF rescues atrophic cholinergic neurons of the basal forebrain and septum in aged rats ‘I. * Fischer et al., Nature 329: 65-68; 1987
CORTICO-STRIATAL GLUTAMATERGIC PATHWAYS MODULATION OF STRIATAL DOPANINE TURNOVER, ASCORBIC ACID CATABOLISM AND BEHAVIOR IN THE RAT P.Enrico, M .S.Desole, M . Niele, L.Fresu, G.Esposito, G. De of Pharmacology - Sassari Natale and E. M iele - Institute Levels of DA,DOPAC,ascorbic acid(M) and dehydroascorbic acid (DHAA) were determined by HPLC in the synaptosomal fraction and whole striatum of rats,whose fronto-parietal cortex had been bilaterally ablated,after a single apomorphine (AP0,l.O mg/kg sc),scopolamine (SCOP, 0,6 mg/kg SC) or d-amphetamine (AMPH, 2.0 mg/kg ip) injection,following a recovery period of 21 days.APO,SCOP and ANPH significantly increased the DHAA/AA ratio in the whole striatum of unoperated and sham operated rats,but failed to increase it in ablated rats.The synapto= somal DHAA/AA ratio was actually decreased in all groups.APO,SCOP and ANPH decreased the DOPAC/DA ratio in the whole striatum of all groups-Cortical ablation potentiated the AMPH-induced and attenuated the SCOP-induced motor hyperactivity.We conclude that APO-,SCOP- and ANPH-induced increase in striatal AA oxidation requires integrity of the cortico-striatal glutamatergic pathways. Furthermore,AA oxidation occurs in the extracellular space. Cortico-striatal glutamatergic pathways modulate both striatal dopaminergic system activity and behavior.Supported by MURST 60%