Differential Regulation of the Expression of Nerve Growth Factor, Brain-Derived Neurotrophic Factor, and Neurotrophin-3 after Excitotoxicity in a Rat Model of Huntington's Disease

Abstract

In the present study we have evaluated changes in nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin 3 (NT-3) mRNA expression induced by different glutamate receptor agonists injected into the neostriatum. Up-regulation of NGF expression was observed at 24 h after intrastriatal quinolinate injection, anN-methyl-d-aspartate receptor agonist, and this increase was maintained up to 7 days after lesion. NGF up-regulation was also apparent in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) treatment from 6 to 16 h postinjection. Instead, BDNF was up-regulated only at 6 h after kainate or AMPA excitotoxicity. Interestingly, NT-3 mRNA was down-regulated from 10 to 16 h following AMPA lesion, while 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid injection enhanced NT-3 mRNA levels at 10 h. Our results show a specific neurotrophin response induced by stimulation of each glutamate receptor. These activity-dependent changes might be involved in neuronal plasticity processes and may underlie the differential vulnerability of striatal neurons observed in neurodegenerative disorders.