scholarly journals Sex-dependent effects of chronic exercise on cognitive flexibility but not hippocampal Bdnf in aging mice

2021 ◽  
Author(s):  
Annabel Short ◽  
Viet Bui ◽  
Isabel Zbukvic ◽  
Anthony Hannan ◽  
Terence Pang ◽  
...  
Keyword(s):  
Young Adult ◽  
Cognitive Flexibility ◽  
Cognitive Abilities ◽  
Conditioned Fear ◽  
Voluntary Exercise ◽  
Running Wheel ◽  
Bdnf Mrna ◽  
Male And Female ◽  
Age Related ◽  
Old Mice

Cognitive impairments associated with advanced age involve alterations in the hippocampus that changes to experience throughout life. The hippocampus is critical for cognitive flexibility involved with extinction and reinstatement of conditioned fear. It is widely accepted that regular exercise can be beneficial for hippocampal function. Therefore, we asked whether chronic voluntary exercise in middle-aged mice can improve extinction and/or reinstatement of conditioned fear compared to standard housing. Eight-month-old male and female C57Bl/6J mice had access to a running wheel or remained in standard housing until 11 months of age. Alongside control standard-housed young adult (3-month-old) mice, they received tone-footshock pairings, which were subsequently extinguished with tone-alone presentations the next day. Half of the mice then received a reminder in the form of a single footshock. Male and female 11-month-old mice housed in standard conditions exhibited impaired reinstatement compared to young adult mice. However, for males that had access to a running wheel from 8 months of age, the reminder treatment rescued reinstatement ability. This was not observed in females. Additionally, exercise during middle age in both sexes increased expression of Bdnf mRNA in the hippocampus, specifically exon 4 mRNA. These results show that, at least for males, physical exercise is beneficial for reducing age-related decline in cognitive abilities. Despite not affecting reinstatement, exercise also increased Bdnf gene expression in the female hippocampus, which could potentially benefit other forms of hippocampus-dependent cognition.

scholarly journals Sex-dependent effects of chronic exercise on cognitive flexibility in aging mice

2020 ◽  
Author(s):  
Annabel K. Short ◽  
Viet Bui ◽  
Isabel C. Zbukvic ◽  
Anthony J. Hannan ◽  
Terence Y. Pang ◽  
...  
Keyword(s):  
Young Adult ◽  
Cognitive Flexibility ◽  
Cognitive Abilities ◽  
Conditioned Fear ◽  
Chronic Exercise ◽  
Running Wheel ◽  
Male And Female ◽  
Age Related ◽  
Reminder Treatment ◽  
Old Mice

AbstractCognitive impairments associated with advanced age are a growing concern in our aging society. Such impairments are associated with alterations in brain structure and function, especially in the hippocampus, which changes to experience throughout life. It is well-known that regular exercise can maintain hippocampus volume. The hippocampus is critical for cognitive flexibility involved with extinction and reinstatement of conditioned fear. Therefore, we asked whether voluntary chronic exercise in middle-aged mice can improve extinction and/or reinstatement of conditioned fear compared to standard housing. Eight-month-old male and female C57Bl/6J mice had access to a running wheel or remained in standard housing until 11 months of age. Alongside control standard-housed young adult (3-month-old) mice, they received tone-footshock pairings, which were subsequently extinguished with tone-alone presentations the next day. Half of the mice then received a reminder treatment in the form of a single footshock. Both male and female 11-month-old mice housed in standard conditions exhibited impaired reinstatement compared to young adult mice. However, for males that had access to a running wheel from 8 months of age, the reminder treatment rescued reinstatement ability. This was not observed in females. Additionally, exercise during middle age in both sexes increased expression of Bdnf mRNA in the hippocampus, specifically exon 4 mRNA. These results show that, at least for males, physical exercise is beneficial for reducing age-related decline in cognitive abilities. Despite not rescuing their impaired reinstatement, exercise also increased Bdnf gene expression in the female hippocampus, which could potentially benefit other forms of hippocampal-dependent cognition.

scholarly journals Stroke Induces a BDNF-Dependent Improvement in Cognitive Flexibility in Aged Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Josh Houlton ◽  
Lisa Y. Y. Zhou ◽  
Deanna Barwick ◽  
Emma K. Gowing ◽  
Andrew N. Clarkson
Keyword(s):  
Animal Model ◽  
Cognitive Flexibility ◽  
Cognitive Deficits ◽  
Cox Regression ◽  
Reversal Task ◽  
Critical Window ◽  
Aged Mice ◽  
Sham Surgery ◽  
Age Related ◽  
Old Mice

Stroke remains a leading cause of disability worldwide. Recently, we have established an animal model of stroke that results in delayed impairment in spatial memory, allowing us to better investigate cognitive deficits. Young and aged brains show different recovery profiles after stroke; therefore, we assessed aged-related differences in poststroke cognition. As neurotrophic support diminishes with age, we also investigated the involvement of brain-derived neurotrophic factor (BDNF) in these differences. Young (3-6 months old) and aged (16-21 months old) mice were trained in operant touchscreen chambers to complete a visual pairwise discrimination (VD) task. Stroke or sham surgery was induced using the photothrombotic model to induce a bilateral prefrontal cortex stroke. Five days poststroke, an additional cohort of aged stroke animals were treated with intracerebral hydrogels loaded with the BDNF decoy, TrkB-Fc. Following treatment, animals underwent the reversal and rereversal task to identify stroke-induced cognitive deficits at days 17 and 37 poststroke, respectively. Assessment of sham animals using Cox regression and log-rank analyses showed aged mice exhibit an increased impairment on VD reversal and rereversal learning compared to young controls. Stroke to young mice revealed no impairment on either task. In contrast, stroke to aged mice facilitated a significant improvement in reversal learning, which was dampened in the presence of the BDNF decoy, TrkB-Fc. In addition, aged stroke control animals required significantly less consecutive days and correction trials to master the reversal task, relative to aged shams, an effect dampened by TrkB-Fc. Our findings support age-related differences in recovery of cognitive function after stroke. Interestingly, aged stroke animals outperformed their sham counterparts, suggesting reopening of a critical window for recovery that is being mediated by BDNF.

Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice

2012 ◽  
Vol 302 (9) ◽  
pp. C1306-C1315 ◽  
Author(s):  
Jeff R. S. Leiter ◽  
Ritika Upadhaya ◽  
Judy E. Anderson
Keyword(s):  
Nitric Oxide ◽  
Voluntary Exercise ◽  
Limiting Factors ◽  
Vascular Density ◽  
Vascular Perfusion ◽  
Cell Hyperplasia ◽  
No Donor ◽  
Age Related ◽  
Old Mice ◽  
Sarcolemmal Integrity

Age-related sarcopenia reduces the size, strength, and function of muscle, and the diameter of muscle fibers. It also disrupts the dystrophin-glycoprotein complex, dislocating nitric oxide synthase 1 (NOS-1) and reducing sarcolemmal integrity. This study of quadriceps muscle in 18-mo-old mice showed that NO-donor treatment with isosorbide dinitrate (I) for 6 wk, in combination with voluntary exercise for 3 wk, increased muscle mass by 25% and stimulated cell proliferation. The resulting fiber hypertrophy was accompanied by a lower ratio of protein:DNA, consistent with myogenic-cell hyperplasia. Treatment enhanced the ratio of NOS-1:β-dystroglycan in correlation with fiber diameter, improved sarcolemmal integrity, and increased vascular density after an increase in vascular endothelial growth factor protein at 3 wk. Results demonstrate that age-related muscle refractoriness to exercise can be overcome with NO-donor treatment. Since activation of muscle stem cells and vascular perfusion are limiting factors in the maintenance, regeneration, and growth of aged muscle, results suggest the feasibility of using NO-donor drugs to combat atrophy and muscle ischemia. Improved function and quality of life from the NO-amplified effects of exercise may be useful in aging and other conditions such as disuse, insulin resistance, or microgravity.

scholarly journals Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo

2019 ◽  
Vol 20 (3) ◽  
pp. 589 ◽  
Author(s):  
Maria Olmedillas del Moral ◽  
Nithi Asavapanumas ◽  
Néstor Uzcátegui ◽  
Olga Garaschuk
Keyword(s):  
Young Adult ◽  
Brain Aging ◽  
Critical Role ◽  
Low Grade ◽  
Middle Aged ◽  
Senescent Phenotype ◽  
Adult Mice ◽  
Age Related ◽  
Old Mice

Brain aging is characterized by a chronic, low-grade inflammatory state, promoting deficits in cognition and the development of age-related neurodegenerative diseases. Malfunction of microglia, the brain-resident immune cells, was suggested to play a critical role in neuroinflammation, but the mechanisms underlying this malfunctional phenotype remain unclear. Specifically, the age-related changes in microglial Ca2+ signaling, known to be linked to its executive functions, are not well understood. Here, using in vivo two-photon imaging, we characterize intracellular Ca2+ signaling and process extension of cortical microglia in young adult (2–4-month-old), middle-aged (9–11-month-old), and old (18–21-month-old) mice. Our data revealed a complex and nonlinear dependency of the properties of intracellular Ca2+ signals on an animal’s age. While the fraction of cells displaying spontaneous Ca2+ transients progressively increased with age, the frequencies and durations of the spontaneous Ca2+ transients followed a bell-shaped relationship, with the most frequent and largest Ca2+ transients seen in middle-aged mice. Moreover, in old mice microglial processes extending toward an ATP source moved faster but in a more disorganized manner, compared to young adult mice. Altogether, these findings identify two distinct phenotypes of aging microglia: a reactive phenotype, abundantly present in middle-aged animals, and a dysfunctional/senescent phenotype ubiquitous in old mice.

Calcium spark properties in ventricular myocytes are altered in aged mice

2006 ◽  
Vol 290 (4) ◽  
pp. H1566-H1574 ◽  
Author(s):  
Susan E. Howlett ◽  
Scott A. Grandy ◽  
Gregory R. Ferrier
Keyword(s):  
Young Adult ◽  
Ventricular Myocytes ◽  
Adult Life ◽  
Field Stimulation ◽  
Calcium Spark ◽  
Age Related ◽  
Transient Rise ◽  
Decay Times ◽  
Old Mice ◽  
Age Related Changes

This study determined whether whole cell Ca2+ transients and unitary sarcoplasmic reticulum (SR) Ca2+ release events are constant throughout adult life or whether Ca2+ release is altered in aging ventricular myocytes. Myocytes were isolated from young adult (∼5 mo old) and aged (∼24 mo old) mice. Spontaneous Ca2+ sparks and Ca2+ transients initiated by field stimulation were detected with fluo-4. All experiments were conducted at 37°C. Ca2+ transient amplitudes were reduced, and Ca2+ transient rise times were abbreviated in aged cells stimulated at 8 Hz compared with young adult myocytes. Furthermore, the incidence and frequency of spontaneous Ca2+ sparks were markedly higher in aged myocytes compared with young adult cells. Spark amplitudes and spatial widths were similar in young adult and aged myocytes. However, spark half-rise times and half-decay times were abbreviated in aged cells compared with younger cells. Resting cytosolic Ca2+ levels and SR Ca2+ stores were assessed by rapid application of caffeine in fura-2-loaded cells. Neither resting Ca2+ levels nor SR Ca2+ content differed between young adult and aged cells. Thus increased spark frequency in aging cells was not attributable to increased SR Ca2+ stores. Furthermore, the decrease in Ca2+ transient amplitude was not due to a decrease in SR Ca2+ load. These results demonstrate that alterations in fundamental SR Ca2+ release units occur in aging ventricular myocytes and raise the possibility that alterations in Ca2+ release may reflect age-related changes in fundamental release events rather than changes in SR Ca2+ stores and diastolic Ca2+ levels.

scholarly journals Differential ageing trajectories in motivation, inhibitory control and cognitive flexibility in Barbary macaques ( Macaca sylvanus )

2020 ◽  
Vol 375 (1811) ◽  
pp. 20190617 ◽  
Author(s):  
Eva-Maria Rathke ◽  
Julia Fischer
Keyword(s):  
Problem Solving ◽  
Inhibitory Control ◽  
Cognitive Flexibility ◽  
Cognitive Abilities ◽  
Macaca Sylvanus ◽  
Barbary Macaques ◽  
Related Variation ◽  
Societal Norms ◽  
Age Related ◽  
Effect Of Age

Across the lifespan, the performance in problem-solving tasks varies strongly, owing to age-related variation in cognitive abilities as well as the motivation to engage in a task. Non-human primates provide an evolutionary perspective on human cognitive and motivational ageing, as they lack an insight into their own limited lifetime, and ageing trajectories are not affected by customs and societal norms. To test age-related variation in inhibitory control, cognitive flexibility and persistence, we presented Barbary macaques ( Macaca sylvanus ), living at La Forêt des Singes in Rocamadour (France), with three problem-solving tasks. We conducted 297 trials with 143 subjects aged 2–30 years. We found no effect of age on success and latency to succeed in the inhibitory control task. In the cognitive flexibility task, 21 out of 99 monkeys were able to switch their strategy, but there was no evidence for an effect of age. Yet, the persistence in the motivation task as well as the overall likelihood to participate in any of the tasks declined with increasing age. These results suggest that motivation declines earlier than the cognitive abilities assessed in this study, corroborating the notion that non-human primates and humans show similar changes in motivation in old age. This article is part of the theme issue ‘Evolution of the primate ageing process'.

scholarly journals TET1-mediated DNA hydroxy-methylation regulates adult remyelination

2019 ◽  
Author(s):  
Sarah Moyon ◽  
Rebecca Frawley ◽  
Katy LH Marshall-Phelps ◽  
Linde Kegel ◽  
Sunniva MK Bøstrand ◽  
...  
Keyword(s):  
Young Adult ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Epigenetic Mark ◽  
Adult Mice ◽  
Age Related ◽  
Genome Wide ◽  
Solute Carrier ◽  
Tet Enzymes ◽  
Old Mice

AbstractAdult myelination is essential for brain function and response to injury, but the molecular mechanisms remain elusive. Here we identify DNA hydroxy-methylation, an epigenetic mark catalyzed by Ten-Eleven translocation (TET) enzymes, as necessary for adult myelin repair.While DNA hydroxy-methylation and high levels of TET1 are detected in young adult mice during myelin regeneration after demyelination, this process is defective in old mice. Constitutive or inducible lineage-specific ablation of Tet1 (but not of Tet2) recapitulate the age-related decline of DNA hydroxy-methylation and inefficient remyelination. Genome-wide hydroxy-methylation and transcriptomic analysis identify numerous TET1 targets, including several members of the solute carrier (Slc) gene family. Lower transcripts for Slc genes, including Slc12a2, are observed in Tet1 mutants and old mice and are associated with swelling at the neuroglial interface, a phenotype detected also in zebrafish slc12a2b mutants.We conclude that TET1-mediated DNA hydroxy-methylation is necessary for adult remyelination after injury.

Cognitive Aging in a Precision Sport Context

1996 ◽  
Vol 1 (3) ◽  
pp. 166-179 ◽  
Author(s):  
Bo Molander ◽  
Lars Bäckman
Keyword(s):  
Older Adult ◽  
Cognitive Abilities ◽  
Cognitive Aging ◽  
Motor Performance ◽  
Intervention Programs ◽  
Laboratory Studies ◽  
High Arousal ◽  
Memory And Attention ◽  
Age Related ◽  
Principal Finding

Highly skilled miniature golf players were examined in a series of field and laboratory studies. The principal finding from these studies is that young and young adult players (range = 15-38 years) score equally well or better in competition than in training whereas older adult players (range = 46-73 years) perform worse in competitive events than under training conditions. It was also found that the impairment in motor performance on the part of the older players is associated with age-related deficits in basic cognitive abilities, such as memory and attention. These results support the hypothesis that older players may be able to compensate for age-related deficits under relaxed conditions, but not under conditions of high arousal. The possibility of improving the performance of the older players in stressful situations by means of various intervention programs is discussed.

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