scholarly journals A238 ABSENCE OF AGE-RELATED MEMORY DECLINE IN GERM-FREE MICE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 288-289
Author(s):  
N Kraimi ◽  
G De Palma ◽  
J Lu ◽  
D Bowdish ◽  
E Verdu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Spatial Memory ◽  
Cognitive Decline ◽  
Memory Performance ◽  
Alternation Rate ◽  
Memory Decline ◽  
Germ Free ◽  
Age Related ◽  
Old Mice ◽  
Young Mice

Abstract Background Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiatry 2019). Microbiota to brain signaling is now well established in mice, but the extent to which this influences age-related memory decline is unknown. Aims Our project aims to determine whether the intestinal microbiota contributes to age-related changes in brain function. We address the hypothesis that age-related cognitive decline is attenuated in the absence of the intestinal microbiota. Methods We studied locomotor behavior and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice. We used the Y-maze test based on a spontaneous alternations task to assess cognition, with alternation rate as a proxy of spatial working memory performance. The locomotor activity was measured using the open-field test. Results GF old mice traveled less distance (458.9 cm) than GF young mice (875.7 cm, p < 0.001) but these differences in locomotor activity did not influence spatial memory performance. Indeed, both GF old and GF young mice had an identical alternation rate of 73.3% (p > 0.05). This contrasted with the memory impairment found in old SPF mice that displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.2%, p = 0.13). Conclusions We conclude that the absence of age-related memory decline in germ-free mice is consistent with a role for the microbiota in the cognitive decline associated with aging, likely through action on the immune system, well documented in SPF mice (Thevaranjan et al., Cell Host & Microbe 2017). We propose that novel microbiota-targeted therapeutic strategies may delay or prevent the cognitive decline of aging. Funding Agencies CIHRBalsam Family Foundation

scholarly journals NREM consolidation and increased spindle counts improve age-related memory impairments and hippocampal representations

2020 ◽  
Author(s):  
Robin K. Yuan ◽  
Matthew R. Lopez ◽  
Manuel-Miguel Ramos-Alavarez ◽  
Marc E. Normandin ◽  
Arthur S. Thomas ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Cognitive Decline ◽  
Recognition Task ◽  
Sleep Architecture ◽  
Sleep Restriction ◽  
Poor Sleep ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Old Mice ◽  
Young Mice

SummaryAge-related changes in sleep patterns have been linked to cognitive decline. Specifically, increasing age is associated with increasing fragmentation of sleep and wake cycles. However, it remains unknown if improvements in sleep architecture can ameliorate cellular and cognitive deficits. We evaluated how changes in sleep architecture following sleep restriction affected hippocampal representations and memory in young and old mice. After training in a hippocampus- dependent object/place recognition task, control animals were allowed to sleep ad libitum, while experimental animals underwent 5 hours of sleep restriction (SR). Interestingly, old SR mice exhibited successful object/place learning comparable to young control mice, whereas young SR and old control mice did not. Successful learning correlated with the presence of two hippocampal cell types: 1) “Context” cells, which remained stable throughout training and testing, and 2) “Object” cells, which shifted their preferred firing location when objects were introduced to the context and moved during testing. As expected, EEG analysis revealed more fragmented sleep and fewer spindles in old controls than young controls during the post-training sleep period. However, following the acute SR session, old animals exhibited increased consolidation of NREM and increased spindle count, while young mice only displayed changes in REM bout length. These results indicate that consolidation of NREM sleep and increases in spindle count serve to ameliorate age-related memory deficits and allow hippocampal representations to adapt to changing environments.eTORC BlurbAge-related cognitive decline is associated with poor sleep quality. This study shows that acute sleep restriction serves to improve memory, hippocampal representations, and sleep quality in old mice, having the opposite effect in young animals. These findings indicate that improving sleep quality may mitigate age-related cognitive decline.HighlightsAcute sleep restriction improves memory in old mice, but adversely affects young onesAcute sleep restriction makes hippocampal representations more flexible in old miceAcute sleep restriction improves sleep quality and increases spindle count in old miceAcute sleep restriction decreases hippocampal flexibility in young mice

scholarly journals Shall We Dance? Dancing Modulates Executive Functions and Spatial Memory

2020 ◽  
Vol 17 (6) ◽  
pp. 1960 ◽  
Author(s):  
Carmen Noguera ◽  
Dolores Carmona ◽  
Adrián Rueda ◽  
Rubén Fernández ◽  
José Manuel Cimadevilla
Keyword(s):  
Spatial Memory ◽  
Executive Functions ◽  
Cognitive Decline ◽  
Memory Performance ◽  
Social Contact ◽  
Parietal Lobes ◽  
Age Related ◽  
Performance Results ◽  
Age Related Cognitive Decline ◽  
Age Range

Background: Aging is generally considered to be related to physical and cognitive decline. This is especially prominent in the frontal and parietal lobes, underlying executive functions and spatial memory, respectively. This process could be successfully mitigated in certain ways, such as through the practice of aerobic sports. With regard to this, dancing integrates physical exercise with music and involves retrieval of complex sequences of steps and movements creating choreographies. Methods: In this study, we compared 26 non-professional salsa dancers (mean age 55.3 years, age-range 49–70 years) with 20 non-dancers (mean age 57.6 years, age-range 49–70 years) by assessing two variables: their executive functions and spatial memory performance. Results: results showed that dancers scored better that non-dancers in our tests, outperforming controls in executive functions-related tasks. Groups did not differ in spatial memory performance. Conclusions: This work suggests that dancing can be a valid way of slowing down the natural age-related cognitive decline. A major limitation of this study is the lack of fitness assessment in both groups. In addition, since dancing combines multiple factors like social contact, aerobic exercise, cognitive work with rhythms, and music, it is difficult to determine the weight of each variable.

scholarly journals Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

2021 ◽  
Vol 7 (21) ◽  
pp. eabe4601
Author(s):  
Sandro Da Mesquita ◽  
Jasmin Herz ◽  
Morgan Wall ◽  
Taitea Dykstra ◽  
Kalil Alves de Lima ◽  
...  
Keyword(s):  
T Cells ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Therapeutic Potential ◽  
T Cell Response ◽  
Age Related ◽  
Lymphatic Vasculature ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Old Mice

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.

scholarly journals Brain Ageing, Cognition and Diet: A Review of the Emerging Roles of Food-Based Nootropics in Mitigating Age-related Memory Decline

2019 ◽  
Vol 12 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Adejoke Yetunde Onaolapo ◽  
Adebimpe Yemisi Obelawo ◽  
Olakunle James Onaolapo
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Antioxidant Defense System ◽  
Food Ingredients ◽  
Memory Decline ◽  
Age Related ◽  
Brain Ageing ◽  
Nootropic Agents ◽  
Age Related Cognitive Decline ◽  
The Impact

Background: Age-related cognitive decline has been suggested to result from an increase in the brain neuron loss, which is attributable to continued derangement of the brain’s oxidant/ antioxidant balance. Increased oxidative stress and a concomitant decrease in the brain’s antioxidant defense system have been associated with functional senescence and organismal ageing. However, nature has configured certain foods to be rich sources of nootropic agents, with research showing that increased consumption of such foods or food ingredients may be protective against ageing-related memory decline. This knowledge is becoming increasingly valuable in an era when the boundary that separates food from medicine is becoming blurred. In this review, we examine extant literature dealing with the impact of ageing on brain structure and function, with an emphasis on the roles of oxidative stress. Secondly, we review the benefits of food-based antioxidants with nootropic effects and/or food-based nootropic agents in mitigating memory decline; with a view to improving our understanding of likely mechanisms. We also highlight some of the limitations to the use of food-based nootropics and suggest ways in which they can be better employed in the clinical management of age-related cognitive decline. Conclusion: While it is known that the human brain endures diverse insults in the process of ageing, food-based nootropics are likely to go a long way in mitigating the impacts of these insults. Further research is needed before we reach a point where food-based nootropics are routinely prescribed.

scholarly journals Necroptosis contributes to chronic inflammation and fibrosis in aging liver

2021 ◽  
Author(s):  
Sabira Mohammed ◽  
Nidheesh Thadathil ◽  
Ramasamy Selvarani ◽  
Evan H Nicklas ◽  
Dawei Wang ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Proinflammatory Cytokines ◽  
Term Treatment ◽  
Low Grade ◽  
Short Term Treatment ◽  
M1 Macrophages ◽  
Cell Death Pathway ◽  
Age Related ◽  
Old Mice ◽  
Young Mice

Inflammaging, characterized by an increase in low-grade chronic inflammation with age, is a hallmark of aging and is strongly associated with various age-related diseases, including chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we tested the hypothesis that age-associated increase in necroptosis contributes to chronic inflammation in aging liver. Phosphorylation of MLKL and MLKL-oligomers, markers of necroptosis, as well as phosphorylation of RIPK3 and RIPK1 were significantly upregulated in the livers of old mice relative to young mice and this increase occurred in the later half of life (i.e., after 18 months of age). Markers of M1 macrophages, expression of proinflammatory cytokines (TNFα, IL6 and IL-1β), and markers of fibrosis were significantly upregulated in the liver with age and the change in necroptosis paralleled the changes in inflammation and fibrosis. Hepatocytes and liver macrophages isolated from old mice showed elevated levels of necroptosis markers as well as increased expression of proinflammatory cytokines relative to young mice. Short term treatment with the necroptosis inhibitor, necrostatin-1s (Nec-1s), reduced necroptosis, markers of M1 macrophages, expression of proinflammatory cytokines, and markers of fibrosis in the livers of old mice. Thus, our data show for the first time that liver aging is associated with increased necroptosis and necroptosis contributes to chronic inflammation in the liver, which in turn appears to contribute to liver fibrosis and possibly CLD.

scholarly journals A Virtual Reality Investigation Of Spontaneous Navigation Strategies And Spatial Memory Performance In Schizophrenia

2021 ◽  
Author(s):  
Leanne K. Wilkins
Keyword(s):  
Virtual Reality ◽  
Spatial Memory ◽  
Cognitive Decline ◽  
Strong Evidence ◽  
Effect Size ◽  
Memory Performance ◽  
Cognitive Map ◽  
Magnitude Effect ◽  
Spatial Strategy ◽  
Navigation Strategies

There is strong evidence that schizophrenia (SCZ) patients perform poorly on spatial memory tasks. We investigated whether these deficits were associated with subdivisions of spatial memory (locale/cognitive map and taxon/response) or whether these deficits represented a general cognitive decline. This study investigated the types of spontaneous navigation strategies used by individuals living with SCZ to solve the 4 on 8 task. It was predicted that SCZ participants who spontaneously chose a spatial strategy would have the longest latencies and make the most errors. Four of five measures of latency and errors produced a medium magnitude effect size (

scholarly journals Learning-Dependent Dendritic Spine Plasticity Is Reduced in the Aged Mouse Cortex

2020 ◽  
Vol 14 ◽  
Author(s):  
Lianyan Huang ◽  
Hang Zhou ◽  
Kai Chen ◽  
Xiao Chen ◽  
Guang Yang
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Learning Ability ◽  
Aged Mouse ◽  
Calcium Activity ◽  
Age Related ◽  
Old Mice ◽  
Young Mice

Aging is accompanied by a progressive decrease in learning and memory function. Synaptic loss, one of the hallmarks of normal aging, likely plays an important role in age-related cognitive decline. But little is known about the impact of advanced age on synaptic plasticity and neuronal function in vivo. In this study, we examined the structural dynamics of postsynaptic dendritic spines as well as calcium activity of layer 5 pyramidal neurons in the cerebral cortex of young and old mice. Using transcranial two-photon microscopy, we found that in both sensory and motor cortices, the elimination rates of dendritic spines were comparable between young (3–5 months) and mature adults (8–10 months), but seemed higher in old mice (>20 months), contributing to a reduction of total spine number in the old brain. During the process of motor learning, old mice compared to young mice had fewer new spines formed in the primary motor cortex. Motor training-evoked somatic calcium activity in layer 5 pyramidal neurons of the motor cortex was also lower in old than young mice, which was associated with the decline of motor learning ability during aging. Together, these results demonstrate the effects of aging on learning-dependent synapse remodeling and neuronal activity in the living cortex and suggest that synaptic deficits may contribute to age-related learning impairment.

scholarly journals L-655,708 does not prevent isoflurane-induced memory deficits in old mice

2019 ◽  
Vol 10 (1) ◽  
pp. 180-186 ◽  
Author(s):  
Teng Gao ◽  
Yue Liu ◽  
Zifang Zhao ◽  
Yuan Luo ◽  
Lifang Wang ◽  
...  
Keyword(s):  
Postoperative Cognitive Dysfunction ◽  
Memory Deficits ◽  
Aminobutyric Acid ◽  
Old Patients ◽  
Memory Decline ◽  
Physiological Conditions ◽  
Impaired Memory ◽  
Subtype A ◽  
Old Mice ◽  
Young Mice

Abstract Background General anesthesia and increasing age are two main risk factors for postoperative cognitive dysfunction (POCD). Effective agents for the prevention or treatment of POCD are urgently needed. L-655,708, an inverse agonist of α5 subunit-containing γ-aminobutyric acid subtype A (α5GABAA) receptors, can prevent anesthesia-induced memory deficits in young animals. However, there is a lack of evidence of its efficacy in old animals. Methodology Young (3- to 5-month-old) and old (18- to 20-month-old) mice were given an inhalation of 1.33% isoflurane for 1 hour and their associative memory was evaluated 24 hours after anesthesia using fear-conditioning tests (FCTs). To evaluate the effect of L-655,708, mice received intraperitoneal injections of L-655,708 (0.7 mg/kg) or vehicle 30 minutes before anesthesia. Results Old mice exhibited impaired memory and lower hippocampal α5GABAA levels than young mice under physiological conditions. Pre-injections of L-655,708 significantly alleviated isoflurane-induced memory decline in young mice, but not in old mice. Conclusions L-655,708 is not as effective for the prevention of POCD in old mice as it is in young mice. The use of inverse agonists of α5GABAA in preventing POCD in old patients should be carefully considered.

scholarly journals Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice

2009 ◽  
Vol 58 (12) ◽  
pp. 1559-1567 ◽  
Author(s):  
Zhihong Ren ◽  
Raina Gay ◽  
Adam Thomas ◽  
Munkyong Pae ◽  
Dayong Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Ex Vivo ◽  
The Elderly ◽  
Mesenteric Lymph ◽  
Age Related ◽  
Serovar Typhimurium ◽  
Lymph Node Cells ◽  
Old Mice ◽  
Effect Of Age ◽  
Young Mice

Ageing is associated with a decline in immune function, which predisposes the elderly to a higher incidence of infections. Information on the mechanism of the age-related increase in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) is limited. In particular, little is known regarding the involvement of the immune response in this age-related change. We employed streptomycin (Sm)-pretreated C57BL/6 mice to develop a mouse model that would demonstrate age-related differences in susceptibility and immune response to S. Typhimurium. In this model, old mice inoculated orally with doses of 3×108 or 1×106 c.f.u. S. Typhimurium had significantly greater S. Typhimurium colonization in the ileum, colon, Peyer's patches, spleen and liver than young mice. Old mice had significantly higher weight loss than young mice on days 1 and 2 post-infection. In response to S. Typhimurium infection, old mice failed to increase ex vivo production of IFN-γ and TNF-α in the spleen and mesenteric lymph node cells to the same degree as observed in young mice; this was associated with their inability to maintain the presence of neutrophils and macrophages at a ‘youthful’ level. These results indicate that Sm-pretreated C57BL/6 old mice are more susceptible to S. Typhimurium infection than young mice, which might be due to impaired IFN-γ and TNF-α production as well as a corresponding change in the number of neutrophils and macrophages in response to S. Typhimurium infection compared to young mice.

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