EVIDENCE FOR ASPARTATE-IMMUNOREACTIVE NEURONS IN THE NEOSTRIATUM OF THE RAT: MODULATION BY THE MESENCEPHALIC DOPAMINE PATHWAY VIA D1-SUBTYPE OF RECEPTOR
Section snippets
EXPERIMENTAL PROCEDURES
Male Sprague-Dawley rats (B & K, Stockholm, Sweden) with access to food and water ad libitum were used in the experiments. The rats were maintained in a temperature-controlled environment on a 12 h light/dark cycle, and all experiments were performed under the light period. The experimental protocols performed in the present study were approved by the Swedish Committee for Ethical Experiments on Laboratory Animals.
RESULTS
All 6-OHDA-lesioned rats showed a strong contralateral rotational behaviour (> 10 turns/min) following SKF 38393 (20 mg/kg, s.c.) or quinpirole (5 mg/kg, s.c.), whether given in a single or four repeated doses. The rotational behaviour induced by SKF 38393 was totally abolished following SCH 23390 (0.5 mg/kg, s.c.). No rotational behaviour was observed following saline.
DISCUSSION
The present results demonstrate that there is a small number of neurons in the neostriatum of the rat which binds antibodies raised against aspartate conjugated with keyhole-limpet hemocyanine. The levels of this aspartate-LI are influenced by DA stimulation, probably via D1 subtype of receptors. Indeed, the strongest staining pattern was seen in the 6-OHDA-deafferented neostriatum following multiple doses of the D1 receptor agonist SKF 38393. [64]The effect was unilateral, suggesting that it
CONCLUSION
An interesting question is whether or not the increase in aspartate levels seen in the rat in the present study can occur also in the human brain. For example, can L-DOPA treatment increase aspartate-levels in the DA denervated Parkinsonian brain, and if so, what are the behavioural and long-term biochemical consequences of an increased aspartate release? Can this increased aspartate release produce overstimulation of glutamate receptors, leading to excitotoxic and to further neurodegenerative
Acknowledgements
This study was supported by grants from the Swedish Medical Research Council (2887, 8669), Marianne och Marcus Wallenbergs Stiftelse, Karolinska Institutes fonder andÅke Wibergs Stiftelse. Z-B. Y. is recipient of a scholarship from Karolinska Institute; E.P. is a recipient of a Parke-Davis Neuroscience Research Centre (Cambridge, U.K.) scholarship. R. R-P. is a recipient of a “Basque Government Postdoctoral Research Fellowship”.
References (87)
- et al.
Purification of specific antibody against aspartate and immunocytochemical localization of aspartergic neurons in the rat brain
Neuroscience
(1987) - et al.
Characterization of cholinergic neurons in the rat neostriatum. A combination of choline acetyltransferase immunocytochemistry
Golgi-impregnation and electron microscopy. Neuroscience
(1984) - et al.
The anatomy of neuropeptide Y-containing neurons in rat brain
Neuroscience
(1985) - et al.
Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system-II
Immunohistochemical analysis. Neuroscience
(1986) - et al.
Light microscopic and ultrastructural localization of immunoreactive substance P in the dorsal horn of monkey spinal cord
Neuroscience
(1982) - et al.
Immunohistochemical localization of aspartate in corticofugal pathways
Neurosci. Lett.
(1991) - et al.
Differential amino acid release in rat neostriatum following lesioning of the cortico-striatal pathway
Brain Res.
(1982) - et al.
Amino acid neurotransmitters and their pathways in the mammalian central nervous system
Neuroscience
(1983) - et al.
Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study
Brain Res.
(1988) - et al.
The release of labelled l-glutamic acid from rat neostriatum in vivo following stimulation of frontal cortex
Neuroscience
(1980)
Neurotransmitter and neuromodulators in the basal ganglia
Trends Neurosci.
Evidence that striatal efferents relate to different dopamine receptors
Brain Res.
SCH 23390— the first selective dopamine D-1 antagonist
Eur. J. Pharmac.
The distribution of enkephalin-immunoreactive cell bodies in the rat central nervous system
Neurosci. Lett.
Immunohistochemical localization of γ-aminobutyric acid- and aspartate-containing neurons in the guinea pig vestibular nuclei
Brain Res.
Amino acid neurotransmission: spotlight on synaptic vesicles
Trends Neurosci.
A glutamatergic corticostriatal pathway
Brain Res.
Mechanism of action of α-latrotoxin: the presynaptic stimulatory toxin of the black widow spider venom
Trends Pharmac. Sci.
Serotonin-, substance P- and glutamate/aspartate-like immunoreactivities in medullo-spinal pathways of rat and primate
Neuroscience
Different neuronal localization of aspartate-like and glutamate-like immunoreactivities in the hippocampus of rat, guinea pig, and Senegalese baboon (Papio papio), with a note on the distribution of gamma-aminobutyrate
Neuroscience
The glutamate decarboxylase-, leucine enkephalin-, methionine enkephalin- and substance P- immunoreactive neurons in the neostriatium of the rat and cat: Evidence for partial population overlap
Neuroscience
Glutamate release in vitro from corticostriatal terminals
Brain Res.
Aspartate-like immunoreactivity in primary afferent neurons
Neuroscience
Excitatory amino acid transmitters and their receptors in neural circuits of the cerebral neocortex. neurosci
Res.
Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system
Brain Res.
Immunohistochemical evidence for a dynorphin immunoreactive striatonigral pathway
Eur. J. Pharmac.
NADPH-diaphorase: a selective histochemical marker for the cholinergic neurons of the pontine reticular formation
Neurosci. Lett.
Excitatory amino acids and central synaptic transmission
Trends Pharmac. Sci.
Evidence for the coexistence of glutamate decarboxylase and met-enkephalin immunoreactivities in axon terminals of rat ventral pallidum
Brain Res.
Neuropeptide Y distribution in rat brain
Science
The K-opioid receptor is primarily postsynaptic: Combined immunohistochemical localization of the receptor and endogenous opioids
Proc. Natn. Acad. Sci. U.S.A.
Effect of cholecystokinin octapeptide on endogenous amino acid release from the rat ventromedial nucleus of the hypothalamus and striatum
J. Neurochem.
Glutamate decarboxylase-immunoreactive structures in the rat neostriatum: a correlated light and electron microscopic study including a combination of Golgi impregnation with immunocytochemistry
J. comp. Neurol.
Excitatory amino acid receptors in the vertebrate central nervous system
Pharmac. Rev.
The pharmacology of amino acids related to γ-aminobutyric acid
Pharmac. Rev.
Glutamate: a neurotransmitter in mammalian brain
J. Neurochem.
Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis
J. Neurosci.
In vivo release of endogeneous amino acids from rat striatum: further evidence for a role of glutamate and aspartate in corticostriatal neurotransmission
J. Neurochem.
Production and characterization of four anti-neuropeptide Y monoclonal antibodies
Hybridoma
Aspartate- and glutamate-like immunoreactivities in rat hippocampal slices: depolarization-induced redistribution and effects of precursors
Eur. J. Neurosci.
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2012, Brain Research BulletinCitation Excerpt :A potential candidate is GABA as the vast majority of neostriatal neurons and intrinsic intrastriatal synapses are GABAergic, the latter arising from GABAergic interneurons and from axon collaterals of spiny projection neurons (Tepper et al., 2004); GABA has also been shown to be increased by CCK-8 (Barnes et al., 1991; Rakovska, 1995b). It could be that the effect is mediated through an increase in aspartate (Asp) as intrinsic Asp neurons (seemingly not colocalized with glutamate) (Pettersson et al., 1996) have also been observed in neostriatum and aspartate is significantly increased by CCK-8 as monitored by in vivo microdialysis (You et al., 1994, 1996). Several lines of evidence indicate a complex interplay between dopamine and CCK-8 in striatum: a coexistence of CCK-8 and dopamine in mesencephalic neurons innervating striatum (Hokfelt et al., 1980), an apparently complex modulatory role of CCK-8 for DA release, as CCK-8 has been reported to either increase (Vickeroy and Bianchi, 1987; Marshall et al., 1990) or decrease DA release (Altar et al., 1988; Lane et al., 1986; Cosi et al., 1989; Rakovska, 1995a), and a reciprocal complex modulatory role of DA for CCK-8 as it has been elucidated that at low doses DA enhances CCK release (due to interaction with the more sensitive D2-receptors) whereas high DA doses reduce neostriatal CCK release (due to DA interaction with D1-receptors (Meyer and Krauss, 1983, Meyer et al., 1984; Conzelmann et al., 1984); mRNA CCK levels in the rat striatum have been shown to be elevated following treatment with DA agonists (Ding and Mocchetti, 1992).
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2011, NeuroscienceCitation Excerpt :Our additional finding showing that changes in the striatal HVA/DA ratios were paralleled by corresponding changes in striatal aspartate levels, adds strength to the above interpretation. Thus, striatal aspartate immunoreactive neurons have been reported to be subjected to modulation by the mesencephalic dopamine pathway, with both upregulation after D-1 receptor stimulation (Pettersson et al., 1996), and selective D1 agonist induced increase of aspartate but not glutamate release, as determined by microdialysis (Herrera-Marschitz et al., 1998). This is in accord with our observations of elevated striatal HVA/DA ratios (as an Index of increased DA release) being accompanied, in the human α-syn group of mice, by elevated striatal aspartate levels, that is, increased release; exposure to Mn decreased striatal DA release (cf. lower HVA/DA ratios) and simultaneously cancelled the aspartate changes.
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2008, Brain Research BulletinImmunohistological characterization of striatal and amygdalar structures in the telencephalon of the fire-bellied toad Bombina orientalis
2005, NeuroscienceCitation Excerpt :In Bombina, the dorsal pallidum differs from the rostrally situated striatum proper by the presence of neuron clusters containing high concentrations of NADPH-diaphorase at its very caudal aspect. Further similarities with the mammalian pattern are the presence of neurons ir for aspartate (Pettersson et al., 1996), calretinin (Cooper and Stanford, 2002; Lévesque et al., 2003) and GABA, although the latter seem to be much less abundant. As in mammals, the striato-pallidum of frogs reveals a high concentration of catecholaminergic fibers (i.e. dopamine) and a homogenous distribution of serotonergic fibers (Pasik et al., 1984; Soghomonian et al., 1987).
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2002, Neurobiology of Disease