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NMDA and non-NMDA receptor-mediated differential Ca2+ load and greater vulnerability of motor neurons in spinal cord cultures.
Neurochem Int. 2008 Jan; 52(1-2):247-55.NI

Abstract

Glutamate receptor activated neuronal cell death has been implicated in the pathogenesis of motor neuron disease but the molecular mechanism responsible for neuronal dysfunction needs to be elucidated. In the present study, we examined the contribution of NMDA and non-NMDA sub-types of glutamate receptors in selective vulnerability of motor neurons. Glutamate receptor activated Ca2+ signaling, mitochondrial functions and neurotoxicity in motor neurons and other spinal neurons were studied in mixed spinal cord primary cultures. Exposure of cells to glutamate receptor agonists glutamate, NMDA and AMPA elevated the intracellular Ca2+, mitochondrial Ca2+ and caused mitochondrial depolarization and cytotoxicity in both motor neurons and other spinal neurons but a striking difference was observed in the magnitude and temporal patterns of the [Ca2+]i responses between the two neuronal cell types. The motor neurons elicited higher Ca2+ load than the other spinal neurons and the [Ca2+]i levels were elevated for a longer duration in motor neurons. AMPA receptor stimulation was more effective than NMDA. Both the NMDA and non-NMDA receptor antagonists APV and NBQX inhibited the Ca2+ entry and decreased the cell death significantly; however, NBQX was more potent than APV. Our results demonstrate that both NMDA and non-NMDA sub-types of glutamate receptors contribute to glutamate-mediated motor neuron damage but AMPA receptors play the major role. AMPA receptor-mediated excessive Ca2+ load and differential handling/regulation of Ca2+ buffering by mitochondria in motor neurons could be central in their selective vulnerability to excitotoxicity.

Authors+Show Affiliations

Department of Biophysics, National Institute of Mental Health and Neuro Sciences, Bangalore 560 029, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17692996

Citation

Sen, Indrani, et al. "NMDA and non-NMDA Receptor-mediated Differential Ca2+ Load and Greater Vulnerability of Motor Neurons in Spinal Cord Cultures." Neurochemistry International, vol. 52, no. 1-2, 2008, pp. 247-55.
Sen I, Joshi DC, Joshi PG, et al. NMDA and non-NMDA receptor-mediated differential Ca2+ load and greater vulnerability of motor neurons in spinal cord cultures. Neurochem Int. 2008;52(1-2):247-55.
Sen, I., Joshi, D. C., Joshi, P. G., & Joshi, N. B. (2008). NMDA and non-NMDA receptor-mediated differential Ca2+ load and greater vulnerability of motor neurons in spinal cord cultures. Neurochemistry International, 52(1-2), 247-55.
Sen I, et al. NMDA and non-NMDA Receptor-mediated Differential Ca2+ Load and Greater Vulnerability of Motor Neurons in Spinal Cord Cultures. Neurochem Int. 2008;52(1-2):247-55. PubMed PMID: 17692996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA and non-NMDA receptor-mediated differential Ca2+ load and greater vulnerability of motor neurons in spinal cord cultures. AU - Sen,Indrani, AU - Joshi,Dinesh C, AU - Joshi,Preeti G, AU - Joshi,Nanda B, Y1 - 2007/07/01/ PY - 2007/03/06/received PY - 2007/06/16/revised PY - 2007/06/19/accepted PY - 2007/8/19/pubmed PY - 2008/5/6/medline PY - 2007/8/19/entrez SP - 247 EP - 55 JF - Neurochemistry international JO - Neurochem Int VL - 52 IS - 1-2 N2 - Glutamate receptor activated neuronal cell death has been implicated in the pathogenesis of motor neuron disease but the molecular mechanism responsible for neuronal dysfunction needs to be elucidated. In the present study, we examined the contribution of NMDA and non-NMDA sub-types of glutamate receptors in selective vulnerability of motor neurons. Glutamate receptor activated Ca2+ signaling, mitochondrial functions and neurotoxicity in motor neurons and other spinal neurons were studied in mixed spinal cord primary cultures. Exposure of cells to glutamate receptor agonists glutamate, NMDA and AMPA elevated the intracellular Ca2+, mitochondrial Ca2+ and caused mitochondrial depolarization and cytotoxicity in both motor neurons and other spinal neurons but a striking difference was observed in the magnitude and temporal patterns of the [Ca2+]i responses between the two neuronal cell types. The motor neurons elicited higher Ca2+ load than the other spinal neurons and the [Ca2+]i levels were elevated for a longer duration in motor neurons. AMPA receptor stimulation was more effective than NMDA. Both the NMDA and non-NMDA receptor antagonists APV and NBQX inhibited the Ca2+ entry and decreased the cell death significantly; however, NBQX was more potent than APV. Our results demonstrate that both NMDA and non-NMDA sub-types of glutamate receptors contribute to glutamate-mediated motor neuron damage but AMPA receptors play the major role. AMPA receptor-mediated excessive Ca2+ load and differential handling/regulation of Ca2+ buffering by mitochondria in motor neurons could be central in their selective vulnerability to excitotoxicity. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/17692996/NMDA_and_non_NMDA_receptor_mediated_differential_Ca2+_load_and_greater_vulnerability_of_motor_neurons_in_spinal_cord_cultures_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(07)00162-3 DB - PRIME DP - Unbound Medicine ER -