Distinct physical condition and social behavior phenotypes of CD157 and CD38 knockout mice during aging

Abstract The ability of CD38 and CD157 to consume nicotinamide adenine dinucleotide (NAD) has received much attention because aging-induced elevation of CD38 expression plays a role in the senescence-related decline in NAD levels. Therefore, it is of interest to examine and compare the effects of age-associated changes on the general health and brain function impairment of Cd157 and Cd38 knockout (CD157 KO and CD38 KO) mice. Body weight and behaviors were measured in 8-week-old (young adult) or 12-month-old (middle-aged) male mice of both KO strains. The locomotor activity, anxiety-like behavior, and social behavior of mice were measured in open field, and three-chamber tests. Middle-aged CD157 KO male mice gained more body weight than young adult mice, while little or no body weight gain was observed in middle-aged CD38 KO mice. Middle-aged CD157 KO mice displayed increased anxiety-like behavior and decreased sociability and interaction compared with young adult KO mice. Middle-aged CD38 KO mice showed less anxiety and hyperactivity than CD157 KO mice, similar to young adult CD38 KO mice. The results reveal marked age-dependent changes in male CD157 KO mice but not in male CD38 KO mice. We discuss the distinct differences in aging effects from the perspective of inhibition of NAD metabolism in CD157 and CD38 KO mice, which may contribute to differential behavioral changes during aging.

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Distinct physical condition and social behavior phenotypes of CD157 and CD38 knockout mice during aging

PLoS ONE ◽

10.1371/journal.pone.0244022 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244022

Author(s):

Maria Gerasimenko ◽

Olga Lopatina ◽

Anna A. Shabalova ◽

Stanislav M. Cherepanov ◽

Alla B. Salmina ◽

...

Keyword(s):

Body Weight ◽

Young Adult ◽

Social Behavior ◽

Body Weight Gain ◽

The Body ◽

Male Mice ◽

Aging Effects ◽

Middle Aged ◽

Nad Metabolism ◽

Cd38 Expression

The ability of CD38 and CD157 to utilize nicotinamide adenine dinucleotide (NAD) has received much attention because the aging-induced elevation of CD38 expression plays a role in the senescence-related decline in NAD levels. Therefore, it is of interest to examine and compare the effects of age-associated changes on the general health and brain function impairment of Cd157 and Cd38 knockout (CD157 KO and CD38 KO) mice. The body weight and behaviors were measured in 8-week-old (young adult) or 12-month-old (middle-aged) male mice of both KO strains. The locomotor activity, anxiety-like behavior, and social behavior of the mice were measured in the open field and three-chamber tests. The middle-aged CD157 KO male mice gained more body weight than young adult KO mice, while little or no body weight gain was observed in the middle-aged CD38 KO mice. Middle-aged CD157 KO mice displayed increased anxiety-like behavior and decreased sociability and interaction compared with young adult KO mice. Middle-aged CD38 KO mice showed less anxiety and hyperactivity than CD157 KO mice, similar to young adult CD38 KO mice. The results reveal marked age-dependent changes in male CD157 KO mice but not in male CD38 KO mice. We discuss the distinct differences in aging effects from the perspective of inhibition of NAD metabolism in CD157 and CD38 KO mice, which may contribute to differential behavioral changes during aging.

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Different types of soluble fermentable dietary fibre decrease food intake, body weight gain and adiposity in young adult male rats

Nutrition & Metabolism ◽

10.1186/1743-7075-11-36 ◽

2014 ◽

Vol 11 (1) ◽

pp. 36 ◽

Cited By ~ 50

Author(s):

Clare L Adam ◽

Patricia A Williams ◽

Matthew J Dalby ◽

Karen Garden ◽

Lynn M Thomson ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Young Adult ◽

Food Intake ◽

Adult Male ◽

Dietary Fibre ◽

Body Weight Gain ◽

Male Rats ◽

Decrease Food Intake ◽

Different Types

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High Dietary Fat and Selenium Concentrations Exert Tissue- and Glutathione Peroxidase 1–Dependent Impacts on Lipid Metabolism of Young-Adult Mice

Journal of Nutrition ◽

10.1093/jn/nxaa130 ◽

2020 ◽

Vol 150 (7) ◽

pp. 1738-1748

Author(s):

Zeping Zhao ◽

Jonggun Kim ◽

Xin Gen Lei

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Young Adult ◽

Glutathione Peroxidase ◽

Control Diet ◽

High Fat ◽

Metabolic Potential ◽

Glutathione Peroxidase 1 ◽

Adult Mice

ABSTRACT Background Excessive dietary selenium (Se; 3 mg/kg) or fat (>25%) intakes and overproduction of glutathione peroxidase 1 (GPX1) adversely affect body lipid metabolism. Objective The objective was to reveal impacts and mechanisms of a moderately high Se and a high fat intake on lipid metabolism in Gpx1 knockout (KO) and wild-type (WT) mice. Methods The KO and WT mice (males, 12-wk-old, body weight = 24.8 ± 0.703 g) were allotted to 4 groups each (n = 5) and fed a sucrose-torula yeast basal diet (5% corn oil) supplemented with 0.3 or 1.0 mg (+Se) Se/kg (as sodium selenite) and 0% or 25% [high-fat (HF)] lard for 6 wk. Multiple physiological and molecular biomarkers (68) related to lipid metabolism and selenogenome expression in plasma, liver, and/or adipose tissue were analyzed by 2-way (+Se by HF) ANOVA. Results Compared with the control diet, the +Se diet decreased (P < 0.05) body-weight gain and plasma and liver concentrations of lipids (22–66%) but elevated (≤1.5-fold, P < 0.05) adipose tissue concentrations of lipids in the WT mice. The +Se diet up- and downregulated (P < 0.05) mRNA and/or protein concentrations of factors related to lipogenesis, selenogenome, and transcription, stress, and cell cycle in the liver (26% to 176-fold) and adipose tissues (14% to 1-fold), respectively, compared with the control diet in the WT mice. Many of these +Se diet effects were different (P < 0.05) from those of the HF diet and were eliminated or altered (P < 0.05) by the KO. Conclusions The +Se and HF diets exerted tissue-specific and GPX1 expression–dependent impacts on lipid metabolism and related gene expression in the young-adult mice. Our findings will help reveal metabolic potential and underlying mechanisms of supplementing moderately high Se to subjects with HF intakes.

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Abstract 123: Age-Related Diminishment of the Subventricular Zone Cytogenic Response and Its Contributions to Motor Recovery After Cortical Infarcts

Stroke ◽

10.1161/str.51.suppl_1.123 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Michael R Williamson ◽

Stephanie Le ◽

Ronald L Franzen ◽

Michael R Drew ◽

Theresa A Jones

Keyword(s):

Young Adult ◽

Subventricular Zone ◽

Motor Recovery ◽

Lineage Tracing ◽

Stem Cell Markers ◽

Middle Aged ◽

Reaching Task ◽

Aged Mice ◽

Adult Mice ◽

Age Related

Stroke increases proliferation within the subventricular zone (SVZ) cytogenic niche and causes subsequent migration of newborn cells towards the site of injury. We investigated the functional consequences of age-related blunting of the SVZ cytogenic response to ischemia. We found that there was a marked reduction in proliferation and neural stem cell markers within the SVZ of middle aged (aged 12-16 months) versus young adult (aged 3-5 months) mice in the intact brain and after photothrombotic infarcts in motor cortex. Using an inducible, heritable lineage tracing system (Nestin-CreER T2 :: Ai14 mice) to quantify SVZ-derived neural precursor cells (NPCs) that migrated towards the infarct, we found that there was a considerable age-related reduction in the number of NPCs in peri-infarct cortex. These findings indicate a marked diminishment of SVZ NPC proliferation and migration after focal ischemia by middle age. Next, we assessed the contributions of the SVZ cytogenic response to recovery of skilled motor function. We used glial fibrillary acidic protein-thymidine kinase mice to conditionally ablate NPCs with ganciclovir administration. In young adult mice, NPC ablation significantly impaired recovery of motor performance on the single seed reaching task after motor cortical infarcts. By contrast, NPC ablation did not affect motor recovery in middle aged mice. Importantly, the magnitude of recovery was less in middle aged mice—regardless of NPC ablation—than in control young adult mice. Middle aged mice recovered similarly to young adult mice lacking NPCs. These results indicate that SVZ cytogenesis contributes to functional improvements after cortical infarcts and that the diminishment of the cytogenic response with age may be implicated in age-related worsening of outcome after stroke. Restoration of SVZ cytogenesis in aged animals might improve behavioral recovery.

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Young-Adult Male Rats’ Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors

Neuroscience Journal ◽

10.1155/2016/5317242 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Herrera-Pérez José Jaime ◽

Benítez-Coronel Venus ◽

Jiménez-Rubio Graciela ◽

Hernández-Hernández Olivia Tania ◽

Martínez-Mota Lucía

Keyword(s):

Body Weight ◽

Weight Gain ◽

Young Adult ◽

Adult Male ◽

Body Weight Gain ◽

Chronic Mild Stress ◽

Male Rats ◽

Mild Stress ◽

Serum Corticosterone ◽

Plus Maze

In a previous study, we found that chronic mild stress (CMS) paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal’s vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals’ body weight and sucrose preference (indicator of anhedonia) were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests); meanwhile, others were used to measure serum corticosterone. We found that CMS (1) did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2) decreased body weight gain; and (3) increased the rat’s entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats’ vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors.

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Regulation of Body Weight and Metabolism by Tanycyte-Derived Neurogenesis in Young Adult Mice

Stem Cells in Neuroendocrinology - Research and Perspectives in Endocrine Interactions ◽

10.1007/978-3-319-41603-8_5 ◽

2016 ◽

pp. 51-67 ◽

Cited By ~ 1

Author(s):

Seth Blackshaw ◽

Daniel A. Lee ◽

Thomas Pak ◽

Sooyeon Yoo

Keyword(s):

Body Weight ◽

Young Adult ◽

Adult Mice

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Fat Mass Regain in Middle-Aged Mice after Sleeve Gastrectomy is divergent from plasma leptin levels

10.1101/2020.10.05.326785 ◽

2020 ◽

Author(s):

Ana BF Emiliano ◽

Ying He ◽

Sei Higuchi ◽

Rabih Nemr ◽

Natalie Lopatinsky ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Fat Mass ◽

Male Mice ◽

Middle Aged ◽

Sham Surgery ◽

Sh Group ◽

Plasma Leptin ◽

Obese Male ◽

Cumulative Food Intake

AbstractBackgroundSome degree of weight regain is typically observed in human patients who undergo Sleeve Gastrectomy (SG), even if the majority of them do not return to their presurgical body weight. Although the majority of bariatric surgery patients are middle aged, most preclinical models of bariatric surgery utilize juvenile male mice. A long-term characterization of the response of mature, wild type, obese male mice to SG has not been performed.MethodsEight-month old C57bl/6J obese male mice were randomized to undergo SG, sham surgery without caloric restriction (SH) or sham surgery with caloric restriction to match body weight to the SG group (SWM). Body weight, body composition and glucose tolerance were matched at baseline. Mice were followed for 60 days following their respective surgeries.ResultsSG mice had a more pronounced percent weight loss than the SH group in the first post-operative month (p<0.05), along with fat mass loss (p<0.01). By the second post-operative month, the SG group started to regain fat mass, although it continued to be statistically lower than the SH group (p<0.05). Cumulative food intake was significantly lower in the SG group compared to SH group only in the first post-operative week (p<0.05), with both groups having similar cumulative food intake thereafter (p>0.05). SWM group had a significantly lower cumulative food intake throughout the study, except for week 1 (p<0.01). Glucose tolerance was only demonstrably better in the SG group compared to SH group at 8 weeks post-operatively (p<0.01). Plasma leptin was significantly lower in the SG group compared to both SWM and SH groups group by the second post-operative month (p<0.01), in spite of SG’s increasing fat mass accumulation. In the second post-operative month, both FGF-21 and GDF-15 were increased in the SH group compared to the SG and SWM groups (p<0.05), while there was no difference in plasma insulin among the three groups. Heat production was surprisingly higher in the SH group compared to the other two groups (p<0.05), even though brown adipose tissue Peroxisome Proliferator-Activated Receptor Gamma (PPARg) and Cidea mRNA expression were significantly higher in SG and SWM compared to SH (p<0.01). There was no change in BAT UCP-1 mRNA expression among the groups (p>0.05). There was also no change in fecal lipid content among the groups (p>0.05).ConclusionsSG in obese, middle aged male mice leads is accompanied by fat mass regain in the second post-operative month, while plasma leptin levels continue to be significantly lower. This raises the question of whether the observed fat mass regain consists mostly of visceral adipose tissue.

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Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms20030589 ◽

2019 ◽

Vol 20 (3) ◽

pp. 589 ◽

Cited By ~ 10

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.

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