Title

The alpha7 nicotinic receptor agonist 4OH-GTS-21 protects axotomized septohippocampal cholinergic neurons in wild type but not amyloid-overexpressing transgenic mice.

Journal

Neuroscience

Volume

148

Issue

None

Pages

230-7

Date

2007-08-10

Authors

Altman M | Hughes JA | King MA | Liu J | Meyer EM | Meyers C | Ren K | Siemann J

Treatment with 4OH-GTS-21 improved performance in both of these paradigms, with drug-induced improvements seen at a lower dose (0.3 mg/kg) in avoidance behavior than in the spatial memory–related task

Improved performance was seen each day in the Morris water task at the 2 mg/kg drug dose compared with saline-injected, lesioned animals

4OH-GTS-21 had no effect on the latency to enter the dark chamber during avoidance training (Fig. 1 ) or on swim speed in the Morris water task (data not shown), indicating that it had no discernible effect on locomotor function

FFX lesions also reduced the size of the septal cholinergic perikarya in saline-injected wild type mice in a manner that was largely prevented by treatment with 4OH-GTS-21 (Fig. 5)

4OH-GTS-21 had no effect on cholinergic cell size in the unlesioned sides of the septa of the wild type or PS1 mice, but did cause atrophy of these neurons in the APP/PS1 mice

4OH-GTS-21 had no protective effect on GABAergic neuronal number in this strain, with FFX lesions causing a 34±9% reduction compared with contralateral controls (n=10; P<0.05 compared with unlesioned side, one-way ANOVA).

The density of this deposition was not affected by 2 weeks of twice per day injections of 1 mg/kg 4OH-GTS-21 (275 deposits/section) or by FFX lesions (37±0.4 deposits/section)

Nine-month-old APP/PS1 mice had significant 6E10- staining amyloid deposition (32±5 deposits/section)

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