Long-term calorie restriction prevented memory impairment in middle-aged male mice and increased a marker of DNA oxidative stress in hippocampal dentate gyrus

Author(s)

Benfato, Izabelle Dias ; Quintanilha, Ana Carolina Silvares ; Henrique, Jessica Salles ; Souza, Melyssa Alves ; Rosario, Barbara dos Anjos ; Beserra-Filho, Jose Ivo Araujo ; Ribeiro, Alessandra Mussi ; Maluf, Luciana Le Sueur ; de Oliveira, Camila Aparecida Machado

• Document type: Journal article
• Source: NEUROBIOLOGY OF LEARNING AND MEMORY; v. 209, p. 10-pg., 2024-02-16.

Abstract

Calorie restriction (CR) is a non-invasive and economic approach known to increase healthspan and life expectancy, through a decrease in oxidative stress, an increase in neurotrophins, among other benefits. However, it is not clear whether its benefit could be noted earlier, as at the beginning of middle -age. Hence, we aimed to determine whether six months of long-term CR, from early adulthood to the beginning of middle age (10 months of age) could positively affect cognitive, neurochemical, and behavioral parameters. Male C57BL6/J mice were randomly distributed into Young Control (YC, ad libitum food), Old Control (OC, ad libitum food), and Old Restricted (OR, 30 % of caloric restriction) groups. To analyze the cognitive and behavioral aspects, the novel object recognition task (NOR), open field, and elevated plus maze tests were performed. In addition, immunohistochemistry targeting Delta FosB (neuronal activity), brain -derived neurotrophic factor (BDNF) and the DNA oxidative damage (8OHdG) in hippocampal subfields CA1, CA2, CA3, and dentate gyrus (DG), and in basolateral amygdala and striatum were performed. Our results showed that long-term CR prevented short-term memory impairment related to aging and increased 8OHdG in hippocampal DG. BDNF was not involved in the effects of either age or CR on memory at middle -age, as it increased in CA3 of the OC group but was not altered in OR. Regarding anxiety -type behavior, no parameter showed differences between the groups. In conclusion, while the effects of long-term CR on anxiety -type behavior were inconclusive, it mitigated the memory deficit related to aging, which was accompanied by an increase in hippocampal 8OHdG in DG. Future studies should investigate whether the benefits of CR would remain if the restriction were interrupted after this long-term protocol. (AU)

• FAPESP's process: 11/05932-3 - Molecular mechanisms involved in the modulation of spontaneous physical activity and development of obesity
• Grantee: Camila Aparecida Machado de Oliveira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/04528-0 - Evaluation of spontaneous physical activity and compensatory behavior in experimental model and obese individuals engaged in an interdisciplinary program for obesity treatment
• Grantee: Camila Aparecida Machado de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/26075-8 - Central control of spontaneous physical activity in mice submitted or not to caloric restriction during aging process
• Grantee: Izabelle Dias Benfato
• Support Opportunities: Scholarships in Brazil - Doctorate