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 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 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 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.

Site density of mouse intestinal glucose transporters declines with age

1993 ◽  
Vol 264 (2) ◽  
pp. G285-G293 ◽  
Author(s):  
R. P. Ferraris ◽  
J. Hsiao ◽  
R. Hernandez ◽  
B. Hirayama
Keyword(s):  
Glucose Transporter ◽  
Glucose Transporters ◽  
Proximal Jejunum ◽  
Site Density ◽  
Phlorizin Binding ◽  
Age Related ◽  
Old Mice ◽  
Effect Of Age ◽  
Distal Jejunum ◽  
Young Mice

To evaluate the effect of age on nutrient transport, the absorption rates of D-glucose, D-fructose, L-alanine, L-aspartate, L-leucine, L-lysine, L-proline, folic acid, and nicotinamide were determined in isolated jejunal tissues of young (6.7 mo old) and aged (23.7 and 27.0 mo old) mice (COBS:SFW). D-Glucose and D-fructose uptakes per milligram tissue were approximately 20-120% higher in the proximal jejunum and 15-50% higher in the distal jejunum of young mice. Amino acid and vitamin uptakes per milligram were also higher in young mice, but differences were not statistically significant. The number of Na(+)-D-glucose transporters per milligram tissue as estimated by specific phlorizin binding decreased with age. There was no age-related change in passive L-glucose permeability, in Kd of specific phlorizin binding, in transporter turnover rate, and in the molecular weight of the Na(+)-D-glucose transporter. Thus a reduction in D-glucose transporter site density fully accounts for the age-related decline in D-glucose transport rate per milligram small intestine.

Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning

2016 ◽  
Vol 298 ◽  
pp. 261-267 ◽  
Author(s):  
David González-Tapia ◽  
Nestor I. Martínez-Torres ◽  
Marisela Hernández-González ◽  
Miguel Angel Guevara ◽  
Ignacio González-Burgos
Keyword(s):  
Prefrontal Cortex ◽  
Motor Learning ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Plastic Changes ◽  
Layer V

scholarly journals Enhancing Motor Learning by Increasing Stability of Newly Formed Dendritic Spines in Motor Cortex

2021 ◽  
Author(s):  
Eddy Albarran ◽  
Aram Raissi ◽  
Omar Jáidar ◽  
Carla J. Shatz ◽  
Jun B. Ding
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Dendritic Spines

scholarly journals Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex

Neuron ◽  
2021 ◽  
Author(s):  
Eddy Albarran ◽  
Aram Raissi ◽  
Omar Jáidar ◽  
Carla J. Shatz ◽  
Jun B. Ding
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Dendritic Spines ◽  
The Stability

scholarly journals Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.

1995 ◽  
Vol 182 (1) ◽  
pp. 129-137 ◽  
Author(s):  
T Zhou ◽  
C K Edwards ◽  
J D Mountz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Cell Function ◽  
Thymic Involution ◽  
Age Related ◽  
Induced Apoptosis ◽  
And Function ◽  
Old Mice ◽  
Young Mice

T cell dysfunction and thymic involution are major immunologic abnormalities associated with aging. Fas (CD95) is a bifunctional molecule that is critical for apoptosis and stimulation during T cell development, but the role of Fas during aging has not been determined. Fas expression and function on T cells from old (22-26-mo-old) mice was compared with young (2-mo-old) mice and old CD2-fas-transgenic mice. Fas expression and ligand-induced apoptosis were decreased on T cells from old mice compared with young mice. This correlated with an age-related increase in CD44+Fas- T cells. There was a marked decrease in the proliferation of T cells from old mice after anti-CD3 stimulation compared with young mice. Anti-CD3-stimulated T cells from young mice exhibited increased production of interleukin (IL)-2 and decreased production of interferon-gamma and IL-10 compared with old mice. There was an age-related decrease in the total thymocyte count from 127 +/- 10 cells in young mice compared with 26 +/- 8 x 10(6) in old mice. In 26-mo-old CD2-fas-transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation, and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis, and that the CD2-fas transgene allows maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.

scholarly journals Age-associated perturbations in glutathione synthesis in mouse liver

2007 ◽  
Vol 405 (3) ◽  
pp. 583-589 ◽  
Author(s):  
Dikran Toroser ◽  
Rajindar S. Sohal
Keyword(s):  
Mouse Liver ◽  
De Novo ◽  
Catalytic Efficiency ◽  
Fold Increase ◽  
Age Related ◽  
Tissue Homogenates ◽  
Synthetic Capacity ◽  
Rate Limiting ◽  
Old Mice ◽  
Young Mice

The nature of the mechanisms underlying the age-related decline in glutathione (GSH) synthetic capacity is at present unclear. Steady-state kinetic parameters of mouse liver GCL (glutamate–cysteine ligase), the rate-limiting enzyme in GSH synthesis, and levels of hepatic GSH synthesis precursors from the trans-sulfuration pathway, such as homocysteine, cystathionine and cysteine, were compared between young and old C57BL/6 mice (6- and 24-month-old respectively). There were no agerelated differences in GCL Vmax, but the apparent Km for its substrates, cysteine and glutamate, was higher in the old mice compared with the young mice (∼800 compared with ∼300 μM, and ∼710 compared with 450 μM, P<0.05 for cysteine and glutamate in young and old mice respectively). Amounts of cysteine, cystathionine and Cys-Gly increased with age by 91, 24 and 28% respectively. Glutathione (GSH) levels remained unchanged with age, whereas GSSG content showed an 84% increase, suggesting a significant pro-oxidizing shift in the 2GSH/GSSG ratio. The amount of the toxic trans-sulfuration/glutathione biosynthetic pathway intermediate, homocysteine, was 154% higher (P<0.005) in the liver of old mice compared with young mice. The conversion of homocysteine into cystathionine, a rate-limiting step in trans-sulfuration catalysed by cystathionine β-synthase, was comparatively less efficient in the old mice, as indicated by cystathionine/homocysteine ratios. Incubation of tissue homogenates with physiological concentrations of homocysteine caused an up to 4.4-fold increase in the apparent Km of GCL for its glutamate substrate, but had no effect on Vmax. The results suggest that perturbation of the catalytic efficiency of GCL and accumulation of homocysteine from the trans-sulfuration pathway may adversely affect de novo GSH synthesis during aging.

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