Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperPre-aggregated Aβ25–35 alters arginine metabolism in the rat hippocampus and prefrontal cortex
Highlights
▶Aβ25–35 altered NOS and arginase activity and protein expression in CA2/3. ▶Aβ25–35 resulted in increased ornithine and putrescine levels in CA2/3. ▶Aβ25–35 led to increased glutamate and putrescine levels in DG. ▶Aβ25–35 decreased agmatine levels in DG and prefrontal cortex. ▶Cluster analyses revealed differences for the hippocampus and prefrontal cortex.
Section snippets
Subjects
Sixteen male Sprague–Dawley rats, weighing between 330 and 400 g, were housed one per cage (33×21.5×17.5 cm3) with free access to food and water, and maintained on a 12-h light/dark cycle (lights on at 8 am). Surgical and behavioral procedures were conducted during the light period of the light–dark cycle. All experimental procedures were carried out in accordance with the regulations of the University of Otago Committee on Ethics in the Care and Use of Laboratory Animals. Every attempt was
Histological results
The cannula tracks were easily identified. For all of the animals, a cannula had been correctly implanted into each lateral ventricle.
Behavioral results
Fig. 2 presents animals' performance in the open field. There were significant differences between the Aβ35–25 and Aβ25–35 groups in terms of the duration of wall-supported rearings (t(14)=2.68, P<0.05; Fig. 2A) and groomings (t(14)=2.34, P<0.05; Fig. 2B), with the latter reared less and groomed more. There were no significant differences between the two groups
Discussion
Previous research has shown that a single i.c.v. infusion of pre-aggregated Aβ25–35 produces behavioral deficits (for a review see Gulyaeva and Stepanichev, 2010). In the present study, animals that received the i.c.v. infusion of Aβ25–35 (30 nmol/rat) displayed less wall-supported rearings, more groomings, and no change in terms of the path length traveled, the percentage of maze used, the percentage of time moving, and the percentage of time spent in the outer zone of the open-field apparatus
Conclusion
The present study demonstrated that a single bilateral i.c.v. infusion of pre-aggregated Aβ25–35 produced behavioral deficits and altered arginine metabolism at the time point of 1 week after Aβ infusion in a region-specific manner. Within the hippocampus, the CA2/3 and DG, but not CA1, appeared to be affected greatly. It has been shown that the DG functions as a “filter/gate” to prevent excessive excitatory input entering CA3, which has an important role in integrating various types of
Acknowledgments
We would like to thank Dr. Tomomi Gotoh for providing arginase II antibody. This work was supported by the Department of Anatomy and Structural Biology, University of Otago. S.A.C. was a recipient of the Allan Wilkinson Summer Studentship Scholarship, Otago Medical Research Foundation.
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