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 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 Heterochronic Parabiosis: Old Blood Induces Changes in Mitochondrial Structure and Function of Young Mice

2020 ◽  
Author(s):  
Jenny L Gonzalez-Armenta ◽  
Ning Li ◽  
Rae-Ling Lee ◽  
Baisong Lu ◽  
Anthony J A Molina
Keyword(s):  
Mitochondrial Respiration ◽  
Complex I ◽  
Structure And Function ◽  
Muscle Performance ◽  
Mitochondrial Morphology ◽  
Positive Effects ◽  
Mitochondrial Structure ◽  
And Function ◽  
Old Mice ◽  
Young Mice

Abstract Heterochronic parabiosis models have been utilized to demonstrate the role of blood-borne circulating factors in systemic effects of aging. In previous studies, heterochronic parabiosis has shown positive effects across multiple tissues in old mice. More recently, a study demonstrated old blood had a more profound negative effect on muscle performance and neurogenesis of young mice. In this study, we used heterochronic parabiosis to test the hypothesis that circulating factors mediate mitochondrial bioenergetic decline, a well-established biological hallmark of aging. We examined mitochondrial morphology, expression of mitochondrial complexes, and mitochondrial respiration from skeletal muscle of mice connected as heterochronic pairs, as well as young and old isochronic controls. Our results indicate that young heterochronic mice had significantly lower total mitochondrial content and on average had significantly smaller mitochondria compared to young isochronic controls. Expression of complex IV followed a similar pattern: young heterochronic mice had a trend for lower expression compared to young isochronic controls. Additionally, respirometric analyses indicate that young heterochronic mice had significantly lower complex I, complex I + II, and maximal mitochondrial respiration and a trend for lower complex II-driven respiration compared to young isochronic controls. Interestingly, we did not observe significant improvements in old heterochronic mice compared to old isochronic controls, demonstrating the profound deleterious effects of circulating factors from old mice on mitochondrial structure and function. We also found no significant differences between the young and old heterochronic mice, demonstrating that circulating factors can be a driver of age-related differences in mitochondrial structure and function.

scholarly journals Location and temporal memory of objects declines in aged marmosets (Callithrix jacchus)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vanessa De Castro ◽  
Pascal Girard
Keyword(s):  
Cognitive Aging ◽  
Home Cage ◽  
Building Blocks ◽  
Memory Deficits ◽  
Primate Model ◽  
Memory Decline ◽  
Temporal Memory ◽  
Inter Trial Interval ◽  
Real Objects ◽  
Spontaneous Exploration

AbstractEpisodic memory decline is an early marker of cognitive aging in human. Although controversial in animals and called “episodic-like memory”, several models have been successfully developed, however they rarely focused on ageing. While marmoset is an emerging primate model in aging science, episodic-like memory has never been tested in this species and importantly in aged marmosets. Here, we examined if the recall of the what-when and what-where building blocks of episodic-like memory declines in ageing marmosets. We developed a naturalistic approach using spontaneous exploration of real objects by young and old marmosets in the home cage. We implemented a three-trial task with 1 week inter-trial interval. Two different sets of identical objects were presented in sample trials 1 and 2, respectively. For the test trial, two objects from each set were presented in a former position and two in a new one. We quantified the exploratory behaviour and calculated discrimination indices in a cohort of 20 marmosets. Young animals presented a preserved memory for combined what-where, and what-when components of the experiment, which declined with aging. These findings lead one to expect episodic-like memory deficits in aged marmosets.

scholarly journals Impact of aging on gene expression response to x-ray irradiation using mouse blood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Constantinos G. Broustas ◽  
Axel J. Duval ◽  
Sally A. Amundson
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
X Rays ◽  
Gene Expression Response ◽  
X Ray ◽  
The Impact ◽  
Old Mice ◽  
Radiation Biodosimetry ◽  
Young Mice

AbstractAs a radiation biodosimetry tool, gene expression profiling is being developed using mouse and human peripheral blood models. The impact of dose, dose-rate, and radiation quality has been studied with the goal of predicting radiological tissue injury. In this study, we determined the impact of aging on the gene expression profile of blood from mice exposed to radiation. Young (2 mo) and old (21 mo) male mice were irradiated with 4 Gy x-rays, total RNA was isolated from whole blood 24 h later, and subjected to whole genome microarray analysis. Pathway analysis of differentially expressed genes revealed young mice responded to x-ray exposure by significantly upregulating pathways involved in apoptosis and phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. In contrast, the functional annotation of senescence was overrepresented among differentially expressed genes from irradiated old mice without enrichment of phagocytosis pathways. Pathways associated with hematologic malignancies were enriched in irradiated old mice compared with irradiated young mice. The fibroblast growth factor signaling pathway was underrepresented in older mice under basal conditions. Similarly, brain-related functions were underrepresented in unirradiated old mice. Thus, age-dependent gene expression differences should be considered when developing gene signatures for use in radiation biodosimetry.

Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice

2016 ◽  
Vol 54 (4) ◽  
pp. 2579-2584 ◽  
Author(s):  
Yue Tian ◽  
Shanbin Guo ◽  
Yan Zhang ◽  
Ying Xu ◽  
Ping Zhao ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
Old Mice

scholarly journals Role of spinal GABAA receptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

2014 ◽  
Vol 306 (7) ◽  
pp. F781-F789 ◽  
Author(s):  
Zhiying Xiao ◽  
Jeremy Reese ◽  
Zeyad Schwen ◽  
Bing Shen ◽  
Jicheng Wang ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Bladder Capacity ◽  
Aminobutyric Acid ◽  
Saline Control ◽  
Receptor Subtype ◽  
High Dose ◽  
Multiple Threshold ◽  
Bladder Activity ◽  
Subtype A

Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly ( P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly ( P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly ( P < 0.05) reduced 2T PNS inhibition at low doses (0.01–0.1 mg/kg). During saline cystometry, PNS significantly ( P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03–0.3 mg/kg iv) also significantly ( P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.

scholarly journals Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jung-Eun Lee ◽  
Hye-Jin Kwon ◽  
Juli Choi ◽  
Ji-Seon Seo ◽  
Pyung-Lim Han
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Chronic Stress ◽  
Brain Aging ◽  
Aged Mice ◽  
Upstream Regulator ◽  
Underlying Mechanisms ◽  
Old Mice ◽  
And Oxidative Stress ◽  
Young Mice

AbstractBrain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus—changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus.

Aging impairs alveolar epithelial type II cell function in acute lung injury

2020 ◽  
Vol 319 (5) ◽  
pp. L755-L769 ◽  
Author(s):  
Tolga Yazicioglu ◽  
Christian Mühlfeld ◽  
Chiara Autilio ◽  
Cheng-Kai Huang ◽  
Christian Bär ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Function ◽  
Lung Injury ◽  
Cell Senescence ◽  
Proliferation Rate ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Surfactant Activity ◽  
Old Mice ◽  
Young Mice

Morbidity and mortality rates in acute lung injury (ALI) increase with age. As alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.5 μg lipopolysaccharide/g body weight in young (3 mo) and old (18 mo) mice that were euthanized 24 h, 72 h, and 10 days later. Lung function, pulmonary surfactant activity, stereology, cell senescence, and single-cell RNA sequencing analyses were performed to investigate AE2 function in aging and ALI. In old mice, surfactant activity was severely impaired. A 60% mortality rate and lung function decline were observed in old, but not in young, mice with ALI. AE2 of young mice adapted to injury by increasing intracellular surfactant volume and proliferation rate. In old mice, however, this adaptive response was compromised, and AE2 of old mice showed signs of cell senescence, increased inflammatory signaling, and impaired surfactant metabolism in ALI. These findings provide evidence that ALI promotes a limited proliferation rate, increased inflammatory response, and surfactant dysfunction in old, but not in young, mice, supporting an impaired regenerative capacity and reduced survival rate in ALI with advancing age.

scholarly journals Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits

2015 ◽  
Vol 53 (10) ◽  
pp. 7271-7283 ◽  
Author(s):  
S. Abad ◽  
J. Camarasa ◽  
D. Pubill ◽  
A. Camins ◽  
E. Escubedo
Keyword(s):  
Memory Deficits ◽  
Adaptive Plasticity ◽  
Young Mice

scholarly journals Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yanhua Zhao ◽  
Lili Huang ◽  
Huan Xu ◽  
Guangxi Wu ◽  
Mengyi Zhu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Young Adult ◽  
Postoperative Cognitive Dysfunction ◽  
Underlying Mechanism ◽  
Reference Memory ◽  
Behavior Changes ◽  
Spatial Reference ◽  
Adult Mice ◽  
Spatial Reference Memory ◽  
Old Mice

Postoperative cognitive dysfunction (POCD) increases morbidity and mortality after surgery. But the underlying mechanism is not clear yet. While age is now accepted as the top one risk factor for POCD, results from studies investigating postoperative cognitive functions in adults have been controversial, and data about the very young adult individuals are lacking. The present study investigated the spatial reference memory, IL-1β, IL-6, and microglia activation changes in the hippocampus in 2-month-old mice after anesthesia and surgery. We found that hippocampal IL-1βand IL-6 increased at 6 hours after surgery. Microglia were profoundly activated in the hippocampus 6 to 24 hours after surgery. However, no significant behavior changes were found in these mice. These results indicate that although anesthesia and surgery led to neuroinflammation, the latter was insufficient to impair the spatial reference memory of young adult mice.

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