The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Activation of Group II Metabotropic Glutamate Receptors Inhibits Synaptic Excitation of the Substantia Nigra Pars Reticulata
Open accessAbstract
Loss of nigrostriatal dopaminergic neurons in Parkinson's disease (PD) leads to increased activity of glutamatergic neurons in the subthalamic nucleus (STN). Recent studies reveal that the resultant increase in STN-induced excitation of basal ganglia output nuclei is responsible for the disabling motor impairment characteristic of PD. On the basis of this, it is possible that any manipulation that reduces activity at excitatory STN synapses onto basal ganglia output nuclei could be useful in the treatment of PD. We now report that group II metabotropic glutamate receptors (mGluRs) are presynaptically localized on STN terminals and that activation of these receptors inhibits excitatory transmission at STN synapses. In agreement with the hypothesis that this could provide a therapeutic benefit in PD, a selective agonist of group II mGluRs induces a dramatic reversal of catalepsy in a rat model of PD. These results raise the exciting possibility that selective agonists of group II mGluRs could provide an entirely new approach to the treatment of PD. These novel therapeutic agents would provide a noninvasive pharmacological treatment that does not involve the manipulation of dopaminergic systems, thus avoiding the problems associated with current therapies.
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“It was shown that activation of mGluR2s can also regulate release of other neurotransmitters: it can inhibit GABA release via a presynaptic mechanism (Bradley et al. 2000; Pilc et al. 2008).”
From Short- and Long-Term Consequences of Nicotine Exposure during Adolescence for Prefrontal Cortex Neuronal Network Function (2012) · cites this paper as Bradley et al. 2000
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Cites
Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation
Limousin, P., Pollak, P., Benazzouz, A., Hoffmann, D., Bas, J. L., Perret, J., Benabid, A., & Broussolle, E. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90062-4 · Cited by 1,480
Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease.
Laitinen, L., Bergenheim, A. T., & Hariz, M. (1992) · Journal of Neurosurgery · doi:10.3171/jns.1992.76.1.0053 · Cited by 1,120
Shigemoto, R., Kinoshita, A., Wada, E., Nomura, S., Ohishi, H., Takada, M., Flor, P. J., Neki, A., Abe, T., Nakanishi, S., et al. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-19-07503.1997 · Cited by 1,116
Kita, H., & Kitai, S. T. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902600309 · Cited by 591
Alternative excitotoxic hypotheses
Albin, R. L., & Greenamyre, J. T. (1992) · Neurology · doi:10.1212/wnl.42.4.733 · Cited by 574 · cited 1×
“Furthermore, glutamate has been implicated as an excitotoxic agent in PD (Albin and Greenamyre, 1992; Rodriguez et al., 1998), suggesting that increased excitatory drive to the SNc may contribute to the progressive loss of SNc dopaminergic neurons in PD.”
BackgroundBaron, M. S., Vitek, J. L., Green, J., Kaneoke, Y., Hashimoto, T., Turner, R. S., Woodard, J. L., DeLong, M. R., Bakay, R. A. E., Cole, S. A., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410400305 · Cited by 559
Ohishi, H., Shigemoto, R., Nakanishi, S., & Mizuno, N. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903350209 · Cited by 516
Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat
Testa, C. M., Standaert, D. G., Young, A. R., & Penney, J. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-05-03005.1994 · Cited by 512
Subthalamic nucleus‐mediated excitotoxicity in parkinson's disease: A target for neuroprotection
Rodríguez‐Oroz, M., Obeso, J. A., & Olanow, C. W. (1998) · Annals of Neurology · doi:10.1002/ana.410440726 · Cited by 399
Luján, R., Roberts, J. D. B., Shigemoto, R., Ohishi, H., & Somogyi, P. (1997) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(97)00051-3 · Cited by 395
Research works printed but not linked: 1
- Wichmann T DeLong MR (1997) Physiology of the basal ganglia and pathophysiology of movement disorders of basal ganglia origin. in Movement disorders: neurological principles and practice, ed Watts RL (McGraw-Hill, New York), pp 87–97.
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Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
Jeffrey Conn, P., Christopoulos, A., & Lindsley, C. W. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2760 · Cited by 1,063
Awad, H., Hubert, G. W., Smith, Y., Levey, A. I., & Conn, P. J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-21-07871.2000 · Cited by 423
Self-citationMetabotropic glutamate receptors in the basal ganglia motor circuit
Conn, P. J., Battaglia, G., Marino, M. J., & Nicoletti, F. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1763 · Cited by 344
Self-citationGoriounova, N. A., & Mansvelder, H. D. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012120 · Cited by 307
“It was shown that activation of mGluR2s can also regulate release of other neurotransmitters: it can inhibit GABA release via a presynaptic mechanism (Bradley et al. 2000; Pilc et al. 2008).”
BackgroundGlutamate Receptors as Therapeutic Targets for Parkinsons Disease
Johnson, K. A., Conn, P. J., & Niswender, C. M. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709789824606 · Cited by 251
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Metadata
- Authors
- Bradley, S. R., Marino, M. J., Wittmann, M., Rouse, S. T., Awad, H., Levey, A. I., & Conn, P. J.
- Affiliations
- University of Tübingen (DE)
- Emory University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-05-01
- Volume
- 20
- Issue
- 9
- Pages
- 3085-3094
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6773118
- OpenAlex
- W1926939570
- Cited by
- 141
- References
- 54
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 6
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Journal of Neuroscience Nursing
- Funders
- National Parkinson Foundation
- Emory University
- National Institutes of Health
- U.S. Army
- Parkinsonfonden
- Topics
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- group II metabotropic glutamate receptors, substantia nigra pars reticulata, subthalamic nucleus, Parkinson's disease, basal ganglia, glutamatergic synapses, presynaptic inhibition, catalepsy, mGluR agonists, glutamatergic neurons
- MeSH terms
- Animals, Bridged Bicyclo Compounds, Catalepsy, Haloperidol, Male, Parkinson Disease, Substantia Nigra, Rats, Sprague-Dawley, Receptors, Presynaptic, Receptors, Metabotropic Glutamate, Dopamine Antagonists, Excitatory Amino Acid Agonists, Glutamic Acid, Excitatory Postsynaptic Potentials, Subthalamic Nucleus, Rats
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