Cognitive stimulation during lifetime and in the aged phase improved spatial memory, and altered neuroplasticity and cholinergic markers of mice

Author(s)

Baraldi, Ticiana ^{[1, 2]} ; Schoewe, Natalia Mendes ^{[1, 3, 2]} ; Balthazar, Janaina ^{[1, 3, 2]} ; Monteiro-Silva, Karla Cristina ^{[4, 2]} ; Albuquerque, Marilia Silva ^{[1, 3, 2]} ; Buck, Hudson Sousa ^{[4, 2]} ; Viel, Tania Araujo ^{[1, 3, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Arts Sci & Humanities, Lab Biomed & Biotechnol, BR-03828080 Sao Paulo - Brazil

^[2] Res Grp Neuropharmacol Aging, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Grad Course Pharmacol, BR-05508900 Sao Paulo - Brazil

^[4] Fac Ciencias Med Santa Casa Sao Paulo, Dept Physiol Sci, BR-01221020 Sao Paulo - Brazil

• Document type: Journal article
• Source: Experimental Gerontology; v. 48, n. 8, p. 831-838, AUG 2013.
• Web of Science Citations: 14

Abstract

In the central nervous system, the degree of decline in memory retrieval along the aging process depends on the quantity and quality of the stimuli received during lifetime. The cholinergic system modulates long-term potentiation and, therefore, memory processing. This study evaluated the spatial memory, the synaptic plasticity and the density of cholinergic markers in the hippocampi of mice submitted to cognitive stimulation during lifetime or during their aged phase. Male C(57)Bl/6 mice (2 months old) were exposed to enriched environment during 15 months (EE-15). An age-matched group was left in standard cages during the same period (SC-15). Spatial memory was evaluated using the Barnes maze at 2, 5, 11 and 17 months of age. At the 17-month-old time point, EE-15 mice showed better performance in the spatial memory task (P < 0.05), when compared to C-15 mice. Other two groups of mice were left in regular cages until the age of 15 months, and then one of the groups was transferred to an enriched environment for two months (EE-2). The other group was kept in regular cages (C-2). After two months of stimulation, EE-2 showed a significant increase in spatial memory (P < 0.01). At the end, brains were extracted and kept at -80 degrees C. Slices were obtained from one hemisphere in a cryostat (20 mu m, -18 degrees C) and thaw-mounted on gelatin coated slides. Synaptic densities, cellular bodies, BDNF densities and alpha 4 beta 2 nicotinic cholinergic receptors (nAChR) were evaluated by immunohistochemistry. Autoradiography for alpha 7 nAChR was conducted using {[}I-125]-alpha-bungarotoxin. The other half of the brains was used for Western blotting analysis of choline acetyltransferase (ChAT) density. There was no difference in synaptophysin or MAP-2 densities, but BDNF was increased in some hippocampal areas of EE-15 and EE-2, in comparison to control groups. In the same way, increases in ChAT and alpha 7 densities, but not in alpha 4 beta 2, were observed. Both cognitive stimuli during lifetime or during the aged phase improved spatial memory of mice. No difference in structural plasticity was observed, but the maintenance of memory can be due to improvement in long-term potentiation functionality in the hippocampus, modulated, at least, by BDNF and the cholinergic system. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 07/07433-9 - Evaluation of the nicotinic cholinergic neuroplasticity at the amygdala, after cognitive stimulation, in an animal model of neurodegeneration and in aging
• Grantee: Tânia Araújo Viel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/04215-3 - Aging process and memory behavior in rats: relevance of the cholinergic system
• Grantee: Marilia Silva de Albuquerque
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 11/14636-9 - Relationship between chronic treatment with lithium and the role of cholinergic system in neuroinflammation
• Grantee: Natália Mendes Schowe
• Support Opportunities: Scholarships in Brazil - Master