Synergistic deleterious effect of chronic stress and sodium azide in the mouse hippocampus.

Alzheimer's disease is the most common cause of dementia in the elderly. Although the primary cause of the disease is presently unknown, to date several risk factors have been described. Evidence suggests that one of these risk factors could be chronic stress.

Peripheral inflammation increases the deleterious effect of CNS inflammation on the nigrostriatal dopaminergic system.

Evidence supports the role of inflammation in the development of neurodegenerative diseases. In this work, we are interested in inflammation as a risk factor by itself and not only as a factor contributing to neurodegeneration. We tested the influence of a mild to moderate peripheral inflammation (injection of carrageenan into the paws of rats) on the degeneration of dopaminergic neurons in an animal model based on the intranigral injection of lipopolysaccharide (LPS), a potent inflammatory agent.

Striatal ablation of GABAergic neurons prevents the in vivo neuroprotective effect of DCG-IV against the MPP+-induced neurotoxicity on dopaminergic nerve terminals.

In previous studies we found that intrastriatal DCG-IV administration, an agonist for group II metabotropic glutamate receptor: (i) protected striatal dopaminergic terminals against MPP(+)-induced neurotoxicity (Matarredona et al., 2001); (ii) selectively destroyed striatal GABAergic neurons (Venero et al., 2002) and (iii) induced early robust up-regulation of brain-derived neurotrophic factor (BDNF) in nigral dopaminergic neurons afferents in a target-dependent manner (Rite et al.

Effect of in vivo striatal perfusion of lipopolysaccharide on dopamine metabolites.

We have used the microdialysis technique to perfuse different concentrations of LPS in the rat's striatum 24h after the implantation of a microdialysis probe. Dopamine metabolites in the dialysate obtained from the rat brain were measured by HPLC using electrochemical detection. Results show that intrastriatal perfusion of different concentrations of LPS produced a dose-dependent decrease in the extracellular DOPAC output, with no effect on the extracellular HVA output.