Structural and molecular correlates of cognitive aging in the rat

Abstract

Aging is associated with cognitive decline. Herein, we studied a large cohort of old age and young adult male rats and confirmed that, as a group, old rats display poorer spatial learning and behavioral flexibility than younger adults. Surprisingly, when animals were clustered as good and bad performers, our data revealed that while in younger animals better cognitive performance was associated with longer dendritic trees and increased levels of synaptic markers in the hippocampus and prefrontal cortex, the opposite was found in the older group, in which better performance was associated with shorter dendrites and lower levels of synaptic markers. Additionally, in old, but not young individuals, worse performance correlated with increased levels of BDNF and the autophagy substrate p62, but decreased levels of the autophagy complex protein LC3. In summary, while for younger individuals “bigger is better”, “smaller is better” is a more appropriate aphorism for older subjects.

Vangl2, a core component of the WNT/PCP pathway, regulates adult hippocampal neurogenesis and age-related decline in cognitive flexibility

“…This procedure, called reversal, was sufficient to uncover a deficit in flexibility in mutant adult mice as they were unable to adapt their strategy. This deficit was also evident when mice were retested at middle age, indicating that the early deficit of Vangl2 is consistent with an advanced onset of a decrease in flexibility otherwise observed with normal aging in mice (Matzel et al, 2011;Yang et al, 2019), rats (Mota et al, 2019), non-human primates (Joly et al, 2014) and humans (van Boxtel et al, 1998). It is also interesting to highlight that although repeated training improved performances in control mice, mutant mice did not benefit from this previous training suggesting that they did not remember the task.…”

“…The different processes involved in episodic memory formation, i.e. the ability to encode and retrieve past experiences and to use the learned information in a novel condition, rely upon the hippocampal formation (Eichenbaum et al, 1990;Bunsey and Eichenbaum, 1996), and an impairment of its integrity is considered a key phenomenon in the appearance of age-related memory deficits (Anon, 2016;Gonzalez-Escamilla et al, 2018;Mota et al, 2019).…”

Responsiveness of dentate neurons generated throughout adult life is associated with resilience to cognitive aging

“…These conclusions have been obtained using the hippocampal‐dependent version of the Morris water maze (measuring reference memory with variable starting points), one of the most widely used behavioral tests to study normal aging in rats; this task does not involve food restriction or the administration of shock to encourage participation of old animals and is very sensitive to the aging process (Kennard & Woodruff‐Pak, 2011; Lubec et al., 2019; Mota et al., 2019). Although inter‐individual differences in memory in aged rats have been demonstrated in other type of mazes (Barrett, Bennie, Trieu, Ping, & Tsafoulis, 2009; Temido‐Ferreira et al., 2018), in object location memory tasks (Lux, Masseck, Herlitze, & Sauvage, 2017), and in the hole‐board task (Lubec et al., 2019), we chose to use the water maze because it is the most widely used task to study the implication of adult‐born neurons in aged rats (our own work, (Bizon & Gallagher, 2003; Marrone, Ramirez‐Amaya, & Barnes, 2012)) whereas their role remains largely unexplored using the other tasks.…”

Estradiol promotes and progesterone reduces anxiety-like behavior produced by nicotine withdrawal in rats

“…Individual rats were grouped and differences in physical signs, EPM, LDT, and corticosterone levels were compared using a between subjects t-test. This k-means categorization process has been used to classify older and younger animals according to their performance in working memory and behavioral flexibility tasks (Mota et al, 2019).…”