Adult Mouse Tissues Research Articles

Identification and characterization of testis-specific gene expressions in mouse tissues

The growth and fertilization of germ cells require the identification and characterization of their unique genes. Because the processes that take place in male germ cells are unique; that is, they do not occur in any other tissue. The testis is a specialized male gonad with complicated gene expressions for spermatogenesis and steroidogenesis. RT-PCR analysis was performed to determine whether the candidate genes selected from the NCBI database are true genes with testis-specific expressions in mice. In total, 20 testis-specific genes were selected randomly and examined in 15 adult mouse tissue samples, including the testis. The expression profiles of the 20 selected genes in the 15 mouse tissue samples showed 3 expression categories: ubiquitously expressed genes, which were detected in all types of mouse tissues; the testis-predominant genes, which were not detected in all mouse tissue samples, were strongly expressed in the testis and weakly expressed in a few types mouse tissue; and the testis-specific genes, which were exclusively expressed in the mouse testis, were not observed in non-testicular tissues. Of the 20 characterized genes, the testis-specific genes include Adad1, Dmrtc2, Luzp4, Prm2, Prss54, and Syce1, which may play a role in meiosis and/or spermatogenesis. Therefore, further research is required to elucidate the functional importance of these identified testis-specific genes in mouse male fertility.

Fate mapping reveals compartment-specific clonal expansion of mononuclear phagocytes during kidney disease

Fate mapping reveals compartment-specific clonal expansion of mononuclear phagocytes during kidney disease

Surfactant protein a attenuates generalized and localized neuroinflammation in neonatal mice.

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A-/-) mice were subjected to three models of brain inflammation: systemic sepsis, intraventricular hemorrhage (IVH) and hypoxic-ischemic encephalopathy (HIE). Following each intervention, RNA was isolated from brain tissue and expression of cytokine and SP-A mRNA was determined by real-time quantitative RT-PCR analysis. In the sepsis model, expression of most cytokine mRNAs was significantly increased in brains of WT and SP-A-/- mice with significantly greater expression of all cytokine mRNA levels in SP-A-/- mice compared to WT. In the IVH model, expression of all cytokine mRNAs was significantly increased in WT and SP-A-/- mice and levels of most cytokine mRNAs were significantly increased in SP-A-/- mice compared to WT. In the HIE model, only TNF-α mRNA levels were significantly increased in WT brain tissue while all pro-inflammtory cytokine mRNAs were significantly increased in SP-A-/- mice, and all pro-inflammatory cytokine mRNA levels were significantly higher in SP-A-/- mice compared to WT. SP-A mRNA was not detectable in brain tissue of adult WT mice nor in WT neonates subjected to these models. These results suggest that SP-A-/- neonatal mice subjected to models of neuroinflammation are more susceptible to both generalized and localized neuroinflammation compared to WT mice, thus supporting the hypothesis that SP-A attenuates inflammation in neonatal mouse brain.

Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice.

Phenotypic plasticity can play an important role in the ability of animals to tolerate environmental stress, but the nature and magnitude of plastic responses are often specific to the developmental timing of exposure. Here, we examine changes in gene expression in the diaphragm of highland deer mice (Peromyscus maniculatus) in response to hypoxia exposure at different stages of development. In highland deer mice, developmental plasticity in diaphragm function may mediate changes in several respiratory traits that influence aerobic metabolism and performance under hypoxia. We generated RNAseq data from diaphragm tissue of adult deer mice exposed to (1) life-long hypoxia (before conception to adulthood), (2) post-natal hypoxia (birth to adulthood), (3) adult hypoxia (6-8 weeks only during adulthood) or (4) normoxia. We found five suites of co-regulated genes that are differentially expressed in response to hypoxia, but the patterns of differential expression depend on the developmental timing of exposure. We also identified four transcriptional modules that are associated with important respiratory traits. Many of the genes in these transcriptional modules bear signatures of altitude-related selection, providing an indirect line of evidence that observed changes in gene expression may be adaptive in hypoxic environments. Our results demonstrate the importance of developmental stage in determining the phenotypic response to environmental stressors.

Effects of assisted reproductive technology on gene expression in heart and spleen tissues of adult offspring mouse.

Assisted reproductive technology (ART) is an important part of reproductive medicine, whose possible effects on offspring's health have drawn widespread attention in recent years. However, relevant studies are limited to postnatal short-term follow-up and lack of diverse sample sources analysis other than blood. In this study, a mouse model was used to explore the effects of ART on fetal development and gene expression in the organs of offspring in the adulthood using next-generation sequencing. The sequencing results were then analyzed. The results showed that it caused abnormal expression in 1060 genes and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and the cardiovascular system development also shows enrichment. STRING analysis identified Ccl2, Ptgs2, Rock1, Mapk14, Agt, and Wnt5a as the core interacting factors. DEGs in the spleen are significantly enriched in anti-infection and immune responses, which include the core factors Fos, Jun and Il1r2. Further exploration revealed the abnormal expression of 42 and 5 epigenetic modifiers in the heart and spleen, respectively. The expression of the imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the hearts of ART offspring, and the DNA methylation levels of Igf2- and Mest-imprinting control regions (ICRs) increased abnormally. In the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring and that these changes are related to the aberrant expression of epigenetic regulators.

The effect of co-administration of artemisinin and N-acetyl cysteine on antioxidant status, spermatological parameters and histopathology of testis in adult male mice.

This invivo study aimed to evaluate the effect of various concentrations of artemisinin (Art) alone or together with N-acetyl cysteine (NAC) on spermatological indices, antioxidant status, and histopathological parameters of testicular tissue in adult male mice. Six groups of five healthy male mice (25-30g) were randomly assigned to different experimental groups. These groups received DMSO and corn oil (0.1%) as an Art solvent (Control), 50mgkg-1 Art (Art-50), 250mgkg-1 Art (Art-250), 50mgkg-1 Art+150mgkg-1 NAC (Art-50+NAC-150), 250mgkg-1 Art+150mgkg-1 NAC (Art-250+NAC-150) and 150mgkg-1 NAC (NAC-150) for a period of 7days. Testes and epididymis were prepared to evaluate the malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), spermatological indices, and histological parameters. We showed that the high dose of Art (Art-250) significantly reduced the sperm count, motility, viability, and the activity of CAT and increased the levels of MDA compared to the control group. Also, the overdose of Art caused adverse changes in testicular tissue. Co-administration of NAC with Art (Art-250+NAC-150) corrected the adverse effects of Art. The current study reports that a high dose of Art affects, spermatological parameters, antioxidant/stress oxidative status of the male reproductive system, and NAC is capable neutralize all adverse effects caused by Art.

Klotho promotes AMPK activity and maintains renal vascular integrity by regulating the YAP signaling pathway.

The development and formation of mammalian blood vessels are closely related to the regulation of signal transduction pathways. Klotho/AMPK and YAP/TAZ signaling pathways are closely related to angiogenesis, but the internal relationship between them is not clear. In this study, we found that Klotho heterozygous deletion mice (Klotho+/- mice) had obvious thickening of the renal vascular wall, obvious enlargement of vascular volume, and significant proliferation and pricking of vascular endothelial cells. Western blot showed that the expression levels of total YAP protein, p-YAP protein (Ser127 and Ser397), p-MOB1, MST1, LATS1, and SAV1 in renal vascular endothelial cells were significantly lower in Klotho+/- mice than in wild-type mice. Knockdown of endogenous Klotho in HUVECs accelerated their ability to divide and form vascular branches in the extracellular matrix. Meanwhile, the results of CO-IP western blot showed that the expression of LATS1 and p-LATS1 interacting with AMPK protein decreased significantly, and the ubiquitination level of YAP protein also decreased significantly in vascular endothelial cells of kidney tissue of Klotho+/- mice. Subsequently, continuous overexpression of exogenous Klotho protein in Klotho heterozygous deficient mice effectively reversed the abnormal renal vascular structure by weakening the expression of the YAP signal transduction pathway. Therefore, we confirmed that Klotho and AMPKα proteins were highly expressed in vascular endothelial cells of adult mouse tissues and organs; this resulted in a phosphorylation modification of YAP protein, closed the activity of the YAP/TAZ signal transduction pathway, and inhibited the growth and proliferation of vascular endothelial cells. When Klotho was absent, the phosphorylation modification of YAP protein by AMPKα was inhibited, resulting in the activation of the YAP/TAZ signal transduction pathway and finally inducing the excessive proliferation of vascular endothelial cells.

Comparative expression analysis of TEADs and their splice variants in mouse embryonic stem cells

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles in embryonic stem cell (ESC) renewal and differentiation. Four TEAD transcription factors (Tead1, Tead2, Tead3 and Tead4) and their various splice variants have been discovered in mice, but the expression pattern of them during pluripotency state transition is unclear. Here, we investigated the expression of TEADs and their splice variants in mouse ESCs at different pluripotent/differentiating states and adult mouse tissues. Our results preliminarily revealed the diversity and heterogeneity of TEAD family, which is helpful for understanding their overlapping and distinctive functions. Furthermore, a novel splice variant of Tead1 was identified and named Tead1 isoform 4.

Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice.

Specialized connective tissues, including bone and adipose tissues, control various physiological activities, including mineral and energy homeostasis. However, the identity of stem cells maintaining these tissues throughout adulthood remains elusive. By conducting genetic lineage tracing and cell depletion experiments in newly generated knock-in Cre/CreERT2 lines, we show here that rare Prrx1-expressing cells act as stem cells for bone, white adipose tissue and dermis in adult mice, which are indispensable for the homeostasis and repair of these tissues. Single-cell profiling reveals the cycling and multipotent nature of Prrx1-expressing cells and the stemness of these cells is further validated by transplantation assays. Moreover, we identify the cell surface markers for Prrx1-expressing stem cells and show that the activities of these stem cells are regulated by Wnt signaling. These findings expand our knowledge of connective tissue homeostasis/regeneration and may help improve stem-cell-based therapies.

Differential effects of age, sex and dexamethasone therapy on ACE2/TMPRSS2 expression and susceptibility to SARS-CoV-2 infection.

ACE2 and TMPRSS2 are crucial for SARS-CoV-2 entry into the cell. Although ACE2 facilitates viral entry, its loss leads to promoting the devastating clinical symptoms of COVID-19 disease. Thus, enhanced ACE2/TMPRSS2 expression is likely to increase predisposition of target cells to SARS-CoV-2 infection. However, little evidence existed about the biological kinetics of these two enzymes and whether dexamethasone treatment modulates their expression. Here, we show that the expression of ACE2 at the protein and mRNA levels was significantly higher in the lung and heart tissues of neonatal compared to adult mice. However, the expression of TMPRSS2 was developmentally regulated. Our results may introduce a novel concept for the reduced susceptibility of the young to SARS-CoV-2 infection. Moreover, ACE2 expression but not TMPRSS2 was upregulated in adult female lungs compared to their male counterparts. Interestingly, the ACE2 and TMPRSS2 expressions were upregulated by dexamethasone treatment in the lung and heart tissues in both neonatal and adult mice. Furthermore, our findings provide a novel mechanism for the observed differential therapeutic effects of dexamethasone in COVID-19 patients. As such, dexamethasone exhibits different therapeutic effects depending on the disease stage. This was supported by increased ACE2/TMPRSS2 expression and subsequently enhanced infection of normal human bronchial epithelial cells (NHBE) and Vero E6 cells with SARS-CoV-2 once pre-treated with dexamethasone. Therefore, our results suggest that individuals who take dexamethasone for other clinical conditions may become more prone to SARS-CoV-2 infection.

Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids, prostaglandin E2 and its E-prostanoid receptor 4 receptor (EP4R) have been implicated in blood pressure control. Our previous study found that conditional deletion of EP4R from all tissues in adult mice exacerbates angiotensin II-dependent hypertension, suggesting a powerful effect of EP4R to resist blood pressure elevation. We also found that elimination of EP4R from vascular smooth muscle cells did not affect the severity of hypertension, suggesting nonvascular targets of prostaglandin E mediate this antihypertensive effect. Methods and Results Here we generated mice with cell-specific deletion of EP4R from macrophage-specific EP4 receptor knockouts or kidney epithelial cells (KEKO) to assess the contributions of EP4R in these cells to hypertension pathogenesis. Macrophage-specific EP4 receptor knockouts showed similar blood pressure responses to alterations in dietary sodium or chronic angiotensin II infusion as Controls. By contrast, angiotensin II-dependent hypertension was significantly augmented in KEKOs (mean arterial pressure: 146±3 mm Hg) compared with Controls (137±4 mm Hg; P=0.02), which was accompanied by impaired natriuresis in KEKOs. Because EP4R expression in the kidney is enriched in the collecting duct, we compared responses to amiloride in angiotensin II-infused KEKOs and Controls. Blockade of the epithelial sodium channel with amiloride caused exaggerated natriuresis in KEKOs compared with Controls (0.21±0.01 versus 0.15±0.02 mmol/24 hour per 20 g; P=0.015). Conclusions Our data suggest EP4R in kidney epithelia attenuates hypertension. This antihypertension effect of EP4R may be mediated by reducing the activity of the epithelial sodium channel, thereby promoting natriuresis.

Murine blastocysts generated by in vitro fertilization show increased Warburg metabolism and altered lactate production.

In vitro fertilization (IVF) has resulted in the birth of over 8 million children. Although most IVF-conceived children are healthy, several studies suggest an increased risk of altered growth rate, cardiovascular dysfunction, and glucose intolerance in this population compared to naturally conceived children. However, a clear understanding of how embryonic metabolism is affected by culture condition and how embryos reprogram their metabolism is unknown. Here, we studied oxidative stress and metabolic alteration in blastocysts conceived by natural mating or by IVF and cultured in physiologic (5%) or atmospheric (20%) oxygen. We found that IVF-generated blastocysts manifest increased reactive oxygen species, oxidative damage to DNA/lipid/proteins, and reduction in glutathione. Metabolic analysis revealed IVF-generated blastocysts display decreased mitochondria respiration and increased glycolytic activity suggestive of enhanced Warburg metabolism. These findings were corroborated by altered intracellular and extracellular pH and increased intracellular lactate levels in IVF-generated embryos. Comprehensive proteomic analysis and targeted immunofluorescence showed reduction of lactate dehydrogenase-B and monocarboxylate transporter 1, enzymes involved in lactate metabolism. Importantly, these enzymes remained downregulated in the tissues of adult IVF-conceived mice, suggesting that metabolic alterations in IVF-generated embryos may result in alteration in lactate metabolism. These findings suggest that alterations in lactate metabolism are a likely mechanism involved in genomic reprogramming and could be involved in the developmental origin of health and disease.

Expression Analyses of Polo-Like Kinase 4, a Gene Product Responsible for Autosomal Recessive Microcephaly and Seckel Syndrome, during Mouse Brain Development

Polo-like kinase 4 (Plk4) is a ser/thr kinase, which plays a central role in centriole duplication during the cell cycle. PLK4 gene abnormalities are responsible for autosomal recessive chorioretinopathy-microcephaly syndrome and Seckel syndrome. In this study, we performed expression analyses of Plk4 by focusing on mouse brain development. Western blotting analyses revealed that Plk4 with a molecular mass of ∼100 kDa was broadly expressed in adult mouse tissues with specific subcellular distribution. As to the central nervous system, Plk4 was expressed throughout the developmental process with drastic increase after P15, suggesting an essential role of Plk4 in differentiated neurons. In immunohistochemical analyses with mouse brain at embryonic day 14, Plk4 was detected dominantly at the cell-cell contact sites of neuronal progenitors in the ventricular zone. Plk4 was then diffusely distributed in the cell body of cortical neurons at P7, while it was enriched in the neuropil as well as soma of excitatory neurons in the cerebral cortex and hippocampus and Purkinje cells in the cerebellum at P30. Notably, biochemical fractionation analysis found an enrichment of Plk4 in the postsynaptic density fraction. Then, immunofluorescent analyses showed partial co-localization of Plk4 with excitatory synaptic markers, PSD95 and synaptophysin, in differentiated primary cultured hippocampal neurons. These results suggest that Plk4 takes part in the regulation of synaptic function in differentiated neurons.

Paternal cadmium exposure affects testosterone synthesis by reducing the testicular cholesterol pool in offspring mice

Cadmium（Cd） is a heavy metal that is harmful to human health. Early studies have shown that cadmium can damage testicular structure, affecting testosterone synthesis and spermatogenesis. However, the effect of paternal Cd exposure on the reproductive system of offspring remains unclear. In this study, male 8-week C57BL/6 J mice were used as research objects, and Cd was injected intraperitoneally every other day at a dose of 1 mg/kg for 5 weeks, after which the effect on the reproductive system of offspring male mice was studied. Our results showed that the body weight of the offspring male mice increased faster, with increases of the testicular and epididymis indices under Cd exposure. At the same time, the serum testosterone and free cholesterol decreased, total cholesterol increased, and the sperm concentration decreased. Further qRT-PCR and western blot analyses showed that the expressions of StAR, P450scc, 3β-HSD and 17β-HSD, which are related to testosterone synthesis, was significantly downregulated. Additionally, ATGL, LDLR and SR-BI, which are related to the intracellular cholesterol pool were downregulated, leading to the reduction of the cholesterol pool and the accumulation of lipid droplets. Oil red O and BODIPY staining revealed an increase in the abundance of lipid droplets in testicular tissue of newborn and adult mice. Prediction of tsRNA target genes in the sperm of parents and testicular transcriptome of newborn mice showed that the differentially expressed genes were associated with catabolism of fatty acids, cholesterol and ion channels, while the mitochondrial and lysosome functions of testicular tissue of adult offspring mice were decreased. Overall, our results suggest that paternal Cd exposure reduced the intracellular cholesterol pool of testicular of offspring, affected testosterone synthesis and reproductive system development.

Young transgenic hMTH1 mice are protected against dietary fat-induced metabolic stress-implications for enhanced longevity.

hMTH1 protects against mutation during oxidative stress. It degrades 8‐oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS‐induced senescence, and its overexpression in hMTH1‐Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high‐fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild‐type (WT) and hMTH1‐Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD‐induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD‐induced effects were less severe and hMTH1‐Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non‐growing, differentiated tissues of adult mice. In hMTH1‐Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity.

Comparative Analysis of Gene Expression Profiles in the Adipose Tissue of Obese Adult Mice With Rapid Infantile Growth After Undernourishment In Utero.

Rapid infantile growth (RG) markedly increases the risk of obesity and metabolic disorders in adulthood, particularly among neonates born small. To elucidate the molecular mechanisms by which RG following undernourishment in utero (UN) contributes to the deterioration of adult fat deposition, we developed a UN mouse model using maternal energy restriction, followed by RG achieved by adjustments to 4 pups per litter soon after birth. A high-fat diet (HFD) was fed to weaned pups treated or not (Veh) with tauroursodeoxycholic acid (TU). UN-RG pups showed the deterioration of diet-induced obesity and fat deposition, which was ameliorated by TU. We performed a microarray analysis of epididymal adipose tissue and two gene enrichment analyses (NN-Veh vs UN-RD-Veh and UN-RG-Veh vs UN-RG-TU). The results obtained identified 4 common gene ontologies (GO) terms of inflammatory pathways. In addition to the inflammatory characteristics of 4 GO terms, the results of heatmap and principal component analyses of the representative genes from 4 GO terms, genes of interest (GOI; Saa3, Ubd, S100a8, Hpx, Casp1, Agt, Ptgs2) selected from the 4 GO terms, and immunohistochemistry of macrophages collectively suggested the critical involvement of inflammation in the regulation of fat deposition in the responses to UN and TU. Therefore, the present results support the ‘Developmental Origins of Metaflammation’, the last word of which was recently proposed by the concept of metabolic disorders induced by low-grade systemic inflammation.

Inhibition of aberrant Hif1\u03b1 activation delays intervertebral disc degeneration in adult mice

The intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate (EP) and annulus fibrosus (AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol (2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

GAPDH S-nitrosation contributes to age-related sarcopenia through mediating apoptosis

The age-related loss of muscle mass and muscle function known as sarcopenia is a major public health problem among older people. Recent research suggests that activation of apoptotic signaling is a critical aspect of the pathogenesis of age-related sarcopenia. However, little information exists in the literature about the apoptotic mechanism of sarcopenia in aging. Herein, we report that elevated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) S-nitrosation and apoptosis occur in sarcopenia during natural aging and that translocation of S-nitrosated GAPDH to the nucleus and S-nitrosated GAPDH-mediated apoptosis contributed to sarcopenia. The levels and sites of GAPDH S-nitrosation in muscle tissues of young, adult and old mice were studied with a quantitative S-nitrosation proteomic analysis approach. GAPDH S-nitrosation increased with aging, and the GAPDH modification sites Cys150, Cys154 and Cys245 were identified. The upregulated S-nitrosation of GAPDH relies on inducible nitric oxide synthase (iNOS) rather than enzymes involved in denitrosylation. Treatment with the iNOS inhibitor 1400W or mutation of GAPDH S-nitrosation sites alleviated apoptosis of C2C12 cells, further demonstrating that GAPDH S-nitrosation in aging contributes to sarcopenia. Taken together, these findings reveal a new cellular mechanism underlying age-related sarcopenia, and the demonstration of muscle loss mediated by iNOS-induced GAPDH S-nitrosation suggests a potential therapeutic strategy for sarcopenia.

Unlike Brief Inhibition of Microglia Proliferation after Spinal Cord Injury, Long-Term Treatment Does Not Improve Motor Recovery.

Microglia are major players in scar formation after an injury to the spinal cord. Microglia proliferation, differentiation, and survival are regulated by the colony-stimulating factor 1 (CSF1). Complete microglia elimination using CSF1 receptor (CSF1R) inhibitors worsens motor function recovery after spinal injury (SCI). Conversely, a 1-week oral treatment with GW2580, a CSF1R inhibitor that only inhibits microglia proliferation, promotes motor recovery. Here, we investigate whether prolonged GW2580 treatment further increases beneficial effects on locomotion after SCI. We thus assessed the effect of a 6-week GW2580 oral treatment after lateral hemisection of the spinal cord on functional recovery and its outcome on tissue and cellular responses in adult mice. Long-term depletion of microglia proliferation after SCI failed to improve motor recovery and had no effect on tissue reorganization, as revealed by ex vivo diffusion-weighted magnetic resonance imaging. Six weeks after SCI, GW2580 treatment decreased microglial reactivity and increased astrocytic reactivity. We thus demonstrate that increasing the duration of GW2580 treatment is not beneficial for motor recovery after SCI.

The Protective Effects of Vitamin E against Sertraline-Induced Damage on Testicular Tissue in Adult NMRI Mice

The Protective Effects of Vitamin E against Sertraline-Induced Damage on Testicular Tissue in Adult NMRI Mice