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NMDA receptors mediate an early up-regulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease.
J Neurosci Res. 2009 Aug 01; 87(10):2308-18.JN

Abstract

The clinical symptoms of Parkinson's disease (PD) appear late and only when the degenerative process at the level of the nigrostriatal dopamine (DA) pathway is quite advanced. An increase in brain-derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry to study N-methyl-D-aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6-hydroxydopamine (6-OHDA). A time-dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6-OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase-immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6-OHDA also produced an early and transient augmentation of pan-BDNF, exon II-BDNF, and exon III-BDNF transcripts in the ipsilateral SN. The pan-BDNF and exon II-BDNF transcript increases were completely abolished by the prior systemic administration of MK-801, a selective antagonist of NMDA receptors. MK-801 also blocked the increase in BDNF-IR cells in SN observed 7 days after unilateral 6-OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD.

Authors+Show Affiliations

Laboratory of Biochemical Pharmacology, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. gbustos@bio.puc.clNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19326433

Citation

Bustos, Gonzalo, et al. "NMDA Receptors Mediate an Early Up-regulation of Brain-derived Neurotrophic Factor Expression in Substantia Nigra in a Rat Model of Presymptomatic Parkinson's Disease." Journal of Neuroscience Research, vol. 87, no. 10, 2009, pp. 2308-18.
Bustos G, Abarca J, Bustos V, et al. NMDA receptors mediate an early up-regulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease. J Neurosci Res. 2009;87(10):2308-18.
Bustos, G., Abarca, J., Bustos, V., Riquelme, E., Noriega, V., Moya, C., & Campusano, J. (2009). NMDA receptors mediate an early up-regulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease. Journal of Neuroscience Research, 87(10), 2308-18. https://doi.org/10.1002/jnr.22063
Bustos G, et al. NMDA Receptors Mediate an Early Up-regulation of Brain-derived Neurotrophic Factor Expression in Substantia Nigra in a Rat Model of Presymptomatic Parkinson's Disease. J Neurosci Res. 2009 Aug 1;87(10):2308-18. PubMed PMID: 19326433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA receptors mediate an early up-regulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease. AU - Bustos,Gonzalo, AU - Abarca,Jorge, AU - Bustos,Victor, AU - Riquelme,Eduardo, AU - Noriega,Viviana, AU - Moya,Catherine, AU - Campusano,Jorge, PY - 2009/3/28/entrez PY - 2009/3/28/pubmed PY - 2009/9/1/medline SP - 2308 EP - 18 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 87 IS - 10 N2 - The clinical symptoms of Parkinson's disease (PD) appear late and only when the degenerative process at the level of the nigrostriatal dopamine (DA) pathway is quite advanced. An increase in brain-derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry to study N-methyl-D-aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6-hydroxydopamine (6-OHDA). A time-dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6-OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase-immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6-OHDA also produced an early and transient augmentation of pan-BDNF, exon II-BDNF, and exon III-BDNF transcripts in the ipsilateral SN. The pan-BDNF and exon II-BDNF transcript increases were completely abolished by the prior systemic administration of MK-801, a selective antagonist of NMDA receptors. MK-801 also blocked the increase in BDNF-IR cells in SN observed 7 days after unilateral 6-OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/19326433/NMDA_receptors_mediate_an_early_up_regulation_of_brain_derived_neurotrophic_factor_expression_in_substantia_nigra_in_a_rat_model_of_presymptomatic_Parkinson's_disease_ L2 - https://doi.org/10.1002/jnr.22063 DB - PRIME DP - Unbound Medicine ER -