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Effect of NMDA antagonists on the death of cerebellar granule neurons at different ages.
Neurosci Lett. 2006 May 08; 398(3):241-5.NL

Abstract

Cerebellar granule neurons (CGN) are the most abundant neuronal type in the cerebellum. During development, these cells migrate from the external to the internal granule layer (IGL), where they receive excitatory glutamatergic and cholinergic contacts from mossy fibers. During this period of development a large proportion of CGN are eliminated via apoptosis. In vitro studies have demonstrated that when CGN are obtained from rats at postnatal day 8 (P8), the sustained activation of N-methyl-D-aspartate (NMDA) receptor at 2-4 days in vitro rescues neurons from cell death. The NMDA action on cultured CGN could mimic the in vivo actions of the transient activation of the glutamate receptors by the transmitter released by mossy fibers by P12. However, some results suggest that glutamate stimulation could be relevant for CGN at earlier stages of development. In this study we evaluated the effect of NMDA receptor stimulation or blockade on the cell death of both in vivo and cultured CGN obtained from P2 to P8 rats. Our results showed that the blockade of NMDA receptors with the antagonists D,L-2-amino-5-phosphonovaleric acid or dizocilpine (MK-801) reduces cell survival to 20-40%, whereas NMDA treatment increases neuronal survival by approximately 50-60%. In vivo, the treatment with MK-801 reduced the number of apoptotic CGN in the molecular layer (ML) from P5 to P8. These results suggest that NMDA receptor stimulation plays a critical role in the regulation of CGN death during the first week of rat cerebellar development.

Authors+Show Affiliations

Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D. F., México. salavez@buckinstitute.orgNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16469441

Citation

Alavez, Silvestre, et al. "Effect of NMDA Antagonists On the Death of Cerebellar Granule Neurons at Different Ages." Neuroscience Letters, vol. 398, no. 3, 2006, pp. 241-5.
Alavez S, Blancas S, Morán J. Effect of NMDA antagonists on the death of cerebellar granule neurons at different ages. Neurosci Lett. 2006;398(3):241-5.
Alavez, S., Blancas, S., & Morán, J. (2006). Effect of NMDA antagonists on the death of cerebellar granule neurons at different ages. Neuroscience Letters, 398(3), 241-5.
Alavez S, Blancas S, Morán J. Effect of NMDA Antagonists On the Death of Cerebellar Granule Neurons at Different Ages. Neurosci Lett. 2006 May 8;398(3):241-5. PubMed PMID: 16469441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of NMDA antagonists on the death of cerebellar granule neurons at different ages. AU - Alavez,Silvestre, AU - Blancas,Sugela, AU - Morán,Julio, Y1 - 2006/02/15/ PY - 2005/11/16/received PY - 2005/12/15/revised PY - 2006/01/03/accepted PY - 2006/2/14/pubmed PY - 2006/6/9/medline PY - 2006/2/14/entrez SP - 241 EP - 5 JF - Neuroscience letters JO - Neurosci Lett VL - 398 IS - 3 N2 - Cerebellar granule neurons (CGN) are the most abundant neuronal type in the cerebellum. During development, these cells migrate from the external to the internal granule layer (IGL), where they receive excitatory glutamatergic and cholinergic contacts from mossy fibers. During this period of development a large proportion of CGN are eliminated via apoptosis. In vitro studies have demonstrated that when CGN are obtained from rats at postnatal day 8 (P8), the sustained activation of N-methyl-D-aspartate (NMDA) receptor at 2-4 days in vitro rescues neurons from cell death. The NMDA action on cultured CGN could mimic the in vivo actions of the transient activation of the glutamate receptors by the transmitter released by mossy fibers by P12. However, some results suggest that glutamate stimulation could be relevant for CGN at earlier stages of development. In this study we evaluated the effect of NMDA receptor stimulation or blockade on the cell death of both in vivo and cultured CGN obtained from P2 to P8 rats. Our results showed that the blockade of NMDA receptors with the antagonists D,L-2-amino-5-phosphonovaleric acid or dizocilpine (MK-801) reduces cell survival to 20-40%, whereas NMDA treatment increases neuronal survival by approximately 50-60%. In vivo, the treatment with MK-801 reduced the number of apoptotic CGN in the molecular layer (ML) from P5 to P8. These results suggest that NMDA receptor stimulation plays a critical role in the regulation of CGN death during the first week of rat cerebellar development. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/16469441/Effect_of_NMDA_antagonists_on_the_death_of_cerebellar_granule_neurons_at_different_ages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(06)00005-X DB - PRIME DP - Unbound Medicine ER -