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

Gerasimenko, Maria; Lopatina, Olga; Shabalova, Anna A.; Cherepanov, Stanislav M.; Салмина, А. Б.; Yokoyama, Shigeru; Goto, Hisanori; Okamoto, Hiroshi; Yamamoto, Yasuhiko; Ishihara, Katsuhiko; Higashida, Haruhiro

doi:10.1371/journal.pone.0244022

Cited by 14 publications

(17 citation statements)

References 65 publications

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“…There was a significant interaction between drugs and sex ( p < 0.05). A significantly increased duration in the center of the arena of Cana treated male mice, compared to control males, suggested reduced anxiety‐related behavior, and increased willingness to explore a new environment (Shoji et al, 2016; Gerasimenko et al, 2020). None of these measures was altered in Cana‐treated female mice (Figures 6d‐h).…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM‐HET3 mice

et al. 2022

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The aging brain is characterized by progressive increases in neuroinflammation and central insulin resistance, which contribute to neurodegenerative diseases and cognitive impairment. Recently, the Interventions Testing Program demonstrated that the anti‐diabetes drug, Canagliflozin (Cana), a sodium‐glucose transporter 2 inhibitor, led to lower fasting glucose and improved glucose tolerance in both sexes, but extended median lifespan by 14% in male mice only. Here, we show that Cana treatment significantly improved central insulin sensitivity in the hypothalamus and the hippocampus of 30‐month‐old male mice. Aged males produce more robust neuroimmune responses than aged females. Remarkably, Cana‐treated male and female mice showed significant reductions in age‐associated hypothalamic gliosis with a decrease in inflammatory cytokine production by microglia. However, in the hippocampus, Cana reduced microgliosis and astrogliosis in males, but not in female mice. The decrease in microgliosis was partially correlated with reduced phosphorylation of S6 kinase in microglia of Cana‐treated aged male, but not female mice. Thus, Cana treatment improved insulin responsiveness in aged male mice. Furthermore, Cana treatment improved exploratory and locomotor activity of 30‐month‐old male but not female mice. Taken together, we demonstrate the sex‐specific neuroprotective effects of Cana treatment, suggesting its application for the potential treatment of neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM‐HET3 mice

et al. 2022

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“…It then participates in OT release in the hypothalamus (Jin et al, 2007). Although NR supplementation did not change CD38 expression (Gerasimenko et al, 2020b), in vitro studies have shown that NAD applied to the mouse hypothalamus leads to OT release (Gerasimenko et al, 2020a).…”

Section: Nicotinamide Ribosidementioning

confidence: 99%

“…Recently, it has been shown that NAD is consumed more by an increase in CD38 in aged male mice and, thus, proposed that inhibition of CD38 or an increase in NAD may lead to a longer life span ( Tarragó et al, 2018 ; Gerasimenko et al, 2020a , b ). NAD metabolism also catalyzes the formation of cADPR ( Lee and Zhao, 2019 ).…”

Section: Functional Aspects Of the Oxytocin Transport Or Increases In...mentioning

confidence: 99%

Oxytocin Dynamics in the Body and Brain Regulated by the Receptor for Advanced Glycation End-Products, CD38, CD157, and Nicotinamide Riboside

et al. 2022

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Investigating the neurocircuit and synaptic sites of action of oxytocin (OT) in the brain is critical to the role of OT in social memory and behavior. To the same degree, it is important to understand how OT is transported to the brain from the peripheral circulation. To date, of these, many studies provide evidence that CD38, CD157, and receptor for advanced glycation end-products (RAGE) act as regulators of OT concentrations in the brain and blood. It has been shown that RAGE facilitates the uptake of OT in mother’s milk from the digestive tract to the cell surface of intestinal epithelial cells to the body fluid and subsequently into circulation in male mice. RAGE has been shown to recruit circulatory OT into the brain from blood at the endothelial cell surface of neurovascular units. Therefore, it can be said that extracellular OT concentrations in the brain (hypothalamus) could be determined by the transport of OT by RAGE from the circulation and release of OT from oxytocinergic neurons by CD38 and CD157 in mice. In addition, it has recently been found that gavage application of a precursor of nicotinamide adenine dinucleotide, nicotinamide riboside, for 12 days can increase brain OT in mice. Here, we review the evaluation of the new concept that RAGE is involved in the regulation of OT dynamics at the interface between the brain, blood, and intestine in the living body, mainly by summarizing our recent results due to the limited number of publications on related topics. And we also review other possible routes of OT recruitment to the brain.

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“…Previous studies have shown behavioral deficits in constitutive CD38 KO mice, including anxiety-like behaviors, locomotor activity deficits, and altered parental and social behaviors (23, 28, 31). However, CD38 AS-cKO P10 mice did not show any of these behavioral deficits and demonstrated social memory.…”

Section: Discussionmentioning

confidence: 96%

“…Multiple studies have reported that constitutive CD38 KO mice exhibit impaired social behaviors (28)(29)(30). To investigate whether astrocytic CD38 is involved in social behavior, we conducted a three chamber social approach test of CD38 AS-cKO P10 mice, as shown in Figure 1B.…”

Section: Deletion Of Astroglial Cd38 In Postnatal Brain Impairs Socia...mentioning

confidence: 99%

Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

Hattori

Cherepanov

Sakaga

et al. 2021

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Social behavior is essential for the health, survival and reproduction of animals, yet the role of astrocytes in social behavior is largely unknown. CD38 is critical for social behaviors by regulating oxytocin release from hypothalamic neurons. On the other hand, CD38 is most abundantly expressed in astrocytes especially in the postnatal cortex, and is important for astroglial development. Here, we demonstrate that astroglial CD38 plays a pivotal role in the social behavior. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, specifically impaired social memory without any other behavioral abnormalities. Morphological analysis revealed reductions in spine numbers, mature spines and excitatory synapse numbers in the pyramidal neurons of the medial prefrontal cortex (mPFC) due to deletion of astroglial CD38 in the postnatal brain. Astrocyte-conditioned medium (ACM) of CD38 KO astrocytes reduced synaptogenesis of cortical neurons by reducing extracellular SPARCL1, a synaptogenic protein. Finally, the release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. Our data indicate that astroglial CD38 developmentally regulates social memory and neural circuit formation in the developing brain by promoting synaptogenesis through SPARCL1.

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

Cited by 14 publications

References 65 publications

Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM‐HET3 mice

Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM‐HET3 mice

Oxytocin Dynamics in the Body and Brain Regulated by the Receptor for Advanced Glycation End-Products, CD38, CD157, and Nicotinamide Riboside

Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

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