Age-Related Changes in the N-Methyl-d-aspartate Receptor Binding Sites within the Human Basal Ganglia

Villares, Joào; Stávale, João N.

doi:10.1006/exnr.2001.7737

Cited by 23 publications

(10 citation statements)

References 70 publications

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“…The neostriatal glutamatergic system is presented by efferent endings that originate from the neocortex. Autoradiography revealed high density of NMDA glutamate receptors in NS and their irregular distribution in the basal ganglia [12]. Close morphological and functional relationships were revealed between glutamatergic and nigrostriatal dopaminergic endings in NS.…”

Section: Resultsmentioning

confidence: 96%

Neostriatal glutamatergic system is involved in the pathogenesis of picrotoxin-induced choreomyoclonic hyperkinesis

Yakimovskii

Varshavskaya

2004

Bull Exp Biol Med

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Administration of dizocilpine (MK-801, noncompetitive antagonist of NMDA glutamate receptors) into the neostriatum decreased the reproducibility and duration of hyperkinesis in rats induced by repeated microinjections of GABA(A) receptor antagonist picrotoxin. By contrast, glutamate potentiated the hyperkinetic and convulsive effect of picrotoxin and promoted the inhibition of conditioned avoidance response. Our results indicate that the striatal glutamatergic system is involved in the development of locomotor and cognitive disorders associated with deficiency of the neostriatal GABAergic system and playing a role in the pathogenesis of Huntington's chorea.

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Section: Resultsmentioning

confidence: 96%

Neostriatal glutamatergic system is involved in the pathogenesis of picrotoxin-induced choreomyoclonic hyperkinesis

Yakimovskii

Varshavskaya

2004

Bull Exp Biol Med

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“…The NK1R-SP system also interacts with serotonin, noradrenalin, glutamate and GABA neurotransmitter systems (Bailey et al, 2004 ;Gobbi and Blier, 2005 ;Maubach et al, 2002 ;Millan et al, 2001 ;Santarelli et al, 2001). Within these neurotransmitter systems, a 2 -adrenoceptors, b-adrenoceptors and NMDA receptors have also been reported to decline during ageing in humans and rodents (Pascual et al, 1991 ;Sastre et al, 2001 ;Segovia et al, 2001 ;Villares and Stavale, 2001). In contrast, 5-HT 1A and GABA A receptors do not appear to change with ageing in humans (Parsey et al, 2002 ;Rabiner et al, 2002 ;Suhara et al, 1993).…”

Section: Age and Nk1rmentioning

confidence: 82%

Gender and age affect NK1 receptors in the human brain – a positron emission tomography study with [18F]SPA-RQ

Nyman

Eskola

Kajander

et al. 2006

Int. J. Neuropsychopharm.

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Substance P (SP) is a neurotransmitter and neuromodulator that mediates its effects in the brain predominantly via the neurokinin-1 receptors (NK1Rs). NK1Rs and SP have been shown clinically to be involved in nausea and emesis after chemotherapy (CINV) and have been implicated preclinically in a range of neuropsychiatric disorders but unlike CINV their blockade in these conditions does not have proven clinical value. We investigated whether age and gender affects NK1R binding potential (NK1R-BP; an index of receptor availability) in the living human brain using PET and [18F]SPA-RQ, a highly specific NK1R antagonist. Forty-five healthy volunteers (35 male and 10 female), aged between 19 and 55 years were studied. NK1R-BP was estimated using the simplified reference tissue model with cerebellum as a reference region. A regression analysis indicated that that a loss of NK1R is associated with normal ageing as shown by decreased NK1R-BP (average rate 7% per decade). Statistically significant negative associations between age and NK1R-BP were observed in temporal, parietal and frontal cortex, hippocampus and parahippocampal formation. In addition preliminary data were obtained suggesting possible gender differences in NK1R-BP in the cortex and putamen with females having a lower NK1R-BP. The exact physiological significance of these results remains to be elucidated but conceptually they could be involved in age-related CNS disorders or those with gender differences in prevalence.

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“…Independent studies describe alterations to the glutamatergic system with age and suggest a role for Glu in cognitive functioning, but few animal and no human studies have demonstrated the functional significance of age-related alterations to the glutamatergic system. Autoradiography of postmortem rodent and human tissue demonstrates lower Glu receptor binding with older age in basal ganglia (Mitchell and Anderson 1998;Villares and Stavale 2001), cerebellum (Tsiotos et al 1989;Simonyi et al 2000), and hippocampus (Tamaru et al 1991;Court et al 1993). Chromatrographic assays detect age-related declines in total Glu concentration in homogenized rat cerebrum (Tyce and Wong 1980;Dawson et al 1989;Benuck et al 1995) but not autopsied putamen (Kornhuber et al 1993) or biopsied basal frontal, basal temporo-occipital, temporal, and parietal cortices (Knorle et al 1997) of human tissue.…”

Section: Introductionmentioning

confidence: 99%

Low Striatal Glutamate Levels Underlie Cognitive Decline in the Elderly: Evidence from In Vivo Molecular Spectroscopy

et al. 2008

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Glutamate (Glu), the principal excitatory neurotransmitter of prefrontal cortical efferents, potentially mediates higher order cognitive processes, and its altered availability may underlie mechanisms of age-related decline in frontally based functions. Although animal studies support a role for Glu in age-related cognitive deterioration, human studies, which require magnetic resonance spectroscopy for in vivo measurement of this neurotransmitter, have been impeded because of the similarity of Glu's spectroscopic signature to those of neighboring spectral brain metabolites. Here, we used a spectroscopic protocol, optimized for Glu detection, to examine the effect of age in 3 brain regions targeted by cortical efferents-the striatum, cerebellum, and pons-and to test whether performance on frontally based cognitive tests would be predicted by regional Glu levels. Healthy elderly men and women had lower Glu in the striatum but not pons or cerebellum than young adults. In the combined age groups, levels of striatal Glu (but no other proton metabolite also measured) correlated selectively with performance on cognitive tests showing age-related decline. The selective relations between performance and striatal Glu provide initial and novel, human in vivo support for age-related modification of Glu levels as contributing to cognitive decline in normal aging.

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Age-Related Changes in the N-Methyl-d-aspartate Receptor Binding Sites within the Human Basal Ganglia

Cited by 23 publications

References 70 publications

Neostriatal glutamatergic system is involved in the pathogenesis of picrotoxin-induced choreomyoclonic hyperkinesis

Neostriatal glutamatergic system is involved in the pathogenesis of picrotoxin-induced choreomyoclonic hyperkinesis

Gender and age affect NK1 receptors in the human brain – a positron emission tomography study with [18F]SPA-RQ

Low Striatal Glutamate Levels Underlie Cognitive Decline in the Elderly: Evidence from In Vivo Molecular Spectroscopy

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