Figure 10

Chronic stress increases the lipopolysaccharide-induced loss of dopaminergic neurons in the substantia nigra. (A) Coronal section showing tyrosine hydroxylase (TH) immunoreactivity after the injection of vehicle (arrow) in nonstressed animals. (B) TH immunoreactivity after the injection of vehicle (arrow) in stressed animals. No significant changes can be observed. (C) TH immunoreactivity after the injection of 2 μg of lipopolysaccharide (LPS) into the substantia nigra (SN) of nonstressed rats. There is a loss of dopaminergic neurons around the injection track (arrow). (D) TH immunoreactivity after the injection of 2 μg of LPS into the SN of stressed rats. The loss of neurons is higher around the injection track (arrow). (E) RU486 (mifepristone (11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)) diminished the loss of TH-positive neurons caused by the combined action of LPS and stress. Scale bar: 500 μm. Abbreviations: V, vehicle; S, stress; L, lipopolysaccharide; SL, lipopolysaccharide injected into stressed animals; SLR, lipopolysaccharide injected into stressed animals treated with RU486. (F) Quantification of the number of TH-positive cells. Results are mean ± SD of four independent experiments expressed as TH-positive cells within the bounded area of the SN. P < 0.001 by analysis of variance followed by least significant difference post hoc test for multiple comparisons. a, compared with V; b, compared with S; c, compared with L; d, compared with SL. (G) Immunofluorescence of TH after the injection of 2 μg of LPS into the SN of stressed rats. (H) Immunofluorescence of Iba-1 after the injection of 2 μg of LPS into the SN of stressed rats. (I) Merged image of (G) and (H) showing activated microglia around the dopaminergic neurons. Scale bars in (G) through (I): 100 μm.