Article Figures & Data
Figures
- Figure 1.
Cognitive and neuropathological consequences of saporin lesions. A, Visuo-spatial reference memory, assessed in Y-maze (10 trials: PBS, n = 24; 0.08 μg, n = 30; 0.4 μg, n = 25; 15 trials: PBS, n = 14, 0.08 μg, n = 20; 0.4 μg, n = 10). Main effects by two-way repeated-measures ANOVA are shown in the text. Significant post hoc differences between 0.4 μg mu-p75-sap and all other groups are denoted by *p < 0.05. B, Working memory performance, assessed by T-maze alternation (PBS, n = 29; 0.08 μg, n = 52; 0.4 μg, n = 32). C–E, Representative photomicrographs of ChAT-positive neuronal depletion in the medial septum/diagonal band in PBS (C), 0.08 μg mu-p75-sap (D), and 0.4 μg mu-p75-sap (E). Scale bar: (in E) C–E, 200 μm. F–H, Histochemical AChE enzyme activity using the thiocholine method in the hippocampus of 0.08 μg (G) and 0.4 μg mu-p75-sap-treated (H) animals compared with nonlesioned controls (F). Scale bar: (in H) F–H, 200 μm. I, Correlation between ChAT-positive cells and Y-maze performance in trial block two. J, Mean ChAT-positive cells, in three regions spanning the medial septum/diagonal band, in 0.08 μg mu-p75-sap (n = 13) and PBS controls (n = 6), 50 d postlesion (*p < 0.05, Bonferroni post hoc after significant two-way ANOVA). K, Histochemical AChE enzyme activity in the hippocampus of 0.08 μg mu-p75-sap (n = 15) and PBS controls (n = 5; t test, **p < 0.01). L, ChAT mRNA expression in the medial septum in 0.08 μg mu-p75-sap (n = 10) animals relative to PBS controls (n = 9; t test, *p < 0.05).
- Figure 2.
Acute microglial response to cholinergic lesion. A, B, Quantitative PCR data for TNF-α and SRA2 at 3 and 35 d postinjection of PBS or mu-p75-saporin. ***p < 0.001 by Bonferroni post hoc test after a significant one-way ANOVA. Representative micrographs of microglial IBA-1 immunolabeling in the medial septum and dentate gyrus 6 d after PBS injection (C, D) and 6 d (E, F) or 40 d (G, H) after mu-p75-sap (0.08 μg) injection. Scale bar: (in C) C–H, 100 μm.
- Figure 3.
LPS-induced working memory deficits and cholinergic dependence. A, T-maze alternation of PBS or saporin-lesioned animals challenged intraperitoneally with LPS (100 μg/kg) or sterile saline 40 ± 2 d after surgery (n: PBS + sal, 9; PBS + LPS, 6; SAP + sal, 19; SAP + LPS, 10). Bonferroni post hoc tests after significant two-way repeated-measures ANOVA are indicated by ***p < 0.001 and *p < 0.05. B, Cholinergic dependence of T-maze performance was verified by testing 1 h postsystemic challenge with scopolamine hydrobromide (1 mg/kg, i.p., n = 10) or saline (n = 13). Significant interaction between time and treatment by repeated-measures ANOVA is indicated by **p < 0.01. C, Working memory deficits 3 h post-LPS (100 μg/kg) were partially protected against by the acetylcholinesterase inhibitor donepezil (1 mg/kg, i.p.), administered 1 h after LPS. Statistically significant differences by Bonferroni post hoc test after significant main effects by repeated-measures ANOVA are denoted by *p < 0.05 (p75-sap + donepezil n = 14; p75-sap + LPS n = 16; p75-sap + LPS + donepezil n = 8).
- Figure 4.
CNS inflammatory response to systemic LPS in lesioned animals. Expression of proinflammatory genes IL-1β, TNFα, IL-6, CXCL1, and downstream genes PTX-3 and TNFAIP2 in septum and hippocampus 3 h after LPS (100 μg/kg, i.p.) or saline (40 d postlesion). n = 4 for PBS + saline and n = 5 for other groups. Main effects of LPS (two-way ANOVA) are described in main text.
