AßPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.

The human islet amyloid polypeptide reduces hippocampal tauopathy and behavioral impairments in P301S mice without inducing neurotoxicity or seeding amyloid aggregation.

Recent evidence suggests that human islet amyloid polypeptide (h-IAPP) accumulates in the brains of Alzheimer's disease (AD) patients and may interact with Aß or microtubule associated protein tau to associate with the neurodegenerative process. Increasing evidence indicates a potential protective effect of h-IAPP against Aß-induced neurotoxicity in AD mouse models. However, a direct therapeutic effect of h-IAPP supplementation on tauopathy has not been established. Here, we found that long-term h-IAPP treatment attenuated tau hyperphosphorylation levels and induced neuroinflammation and oxidative damage, prevented synaptic loss and neuronal degeneration in the hippocampus, and alleviated behavioral deficits in P301S transgenic mice (a mouse model of tauopathy). Restoration of insulin sensitization, glucose/energy metabolism, and activated BDNF signaling also contributed to the underlying mechanisms. These findings suggest that seemly h-IAPP has promise for the treatment of neurodegenerative disorders with tauopathy, such as AD.

Novel melatonin-trientine conjugate as potential therapeutic agents for Alzheimer's disease.

Researchers continue to explore drug targets to treat the characteristic pathologies of Alzheimer's disease (AD). Some drugs relieve the pathological processes of AD to some extent, but the failed clinical trials indicate that multifunctional agents seem more likely to achieve the therapy goals for this neurodegenerative disease. Herein, a novel compound named melatonin-trientine (TM) has been covalently synthesized with the natural antioxidant compounds melatonin and the metal ion chelator trientine. After toxicological and pharmacokinetic verification, we elucidated the effects of intraperitoneal administration of TM on AD-like pathology in 6-month-old mice that express both the ß-amyloid (Aß) precursor protein and presenilin-1 (APP/PS1). We found that TM significantly decreased Aß deposition and neuronal degeneration in the brains of the APP/PS1 double transgenic mice. This result may be due to the upregulation of iron regulatory protein-2 (IRP2), insulin degrading enzyme (IDE), and low density lipoprotein receptor related protein 1 (LRP1), which leads to decreases in APP and Aß levels. Additionally, TM may promote APP non-amyloidogenic processing by activating the melatonin receptor-2 (MT2)-dependent signaling pathways, but not MT1. In addition, TM plays an important role in blocking γ-secretase, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal ion dyshomeostasis. Our results suggest that TM may effectively maximize the therapeutic efficacy of targeting multiple mechanisms associated with AD pathology.

Recombinant human lactoferrin attenuates the progression of hepatosteatosis and hepatocellular death by regulating iron and lipid homeostasis in ob/ob mice.

Lactoferrin (Lf), an iron-binding glycoprotein, has been shown to possess antioxidant and anti-inflammatory properties and exert modulatory effects on lipid homeostasis and non-alcoholic fatty liver disease (NAFLD), but our understanding of its regulatory mechanisms is limited and inconsistent. We used leptin-deficient (ob/ob) mice as the rodent model of NAFLD, and administered recombinant human Lf (4 mg per kg body weight) or control vehicle by intraperitoneal injection to evaluate the hepatoprotective effects of Lf. After 40 days of treatment with Lf, insulin sensitivity and hepatic steatosis in ob/ob mice were significantly improved with the down-regulation of sterol regulatory element binding protein-2 (SREBP2), indicating an improvement in hepatic lipid metabolism and function. We further explored the mechanism, and found that Lf may increase the hepatocellular iron output by targeting the hepcidin-ferroportin (FPn) axis, and then maintains the liver oxidative balance through a nonenzymatic antioxidant system, ultimately suppressing the death of hepatocytes. In addition, the cytoprotective role of Lf may be associated with the inhibition of endoplasmic reticulum (ER) stress and inflammation, promotion of autophagy of damaged hepatocytes and induction of up-regulation of hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-lα/VEGF) to facilitate liver function recovery. These findings suggest that recombinant human Lf might be a potential therapeutic agent for mitigating or delaying the pathological process of NAFLD.

Copper chelators promote nonamyloidogenic processing of AßPP via MT1/2 /CREB-dependent signaling pathways in AßPP/PS1 transgenic mice.

Copper is essential for the generation of reactive oxygen species (ROS), which are induced by amyloid-ß (Aß) aggregation; thus, the homeostasis of copper is believed to be a therapeutic target for Alzheimer's disease (AD). Although clinical trials of copper chelators show promise when applied in AD, the underlying mechanism is not fully understood. Here, we reported that copper chelators promoted nonamyloidogenic processing of AßPP through MT1/2 /CREB-dependent signaling pathways. First, we found that the formation of Aß plaques in the cortex was significantly reduced, and learning deficits were significantly improved in AßPP/PS1 transgenic mice by copper chelator tetrathiomolybdate (TM) administration. Second, TM and another copper chelator, bathocuproine sulfonate (BCS), promoted nonamyloidogenic processing of AßPP via inducing the expression of ADAM10 and the secretion of sAßPPα. Third, the inducible ADAM10 production caused by copper chelators can be blocked by a melatonin receptor (MT1/2 ) antagonist (luzindole) and a MT2 inhibitor (4-P-PDOT), suggesting that the expression of ADAM10 depends on the activation of MT1/2 signaling pathways. Fourth, three of the MT1/2 -downstream signaling pathways, Gq/PLC/MEK/ERK/CREB, Gs/cAMP/PKA/ERK/CREB and Gs/cAMP/PKA/CREB, were responsible for copper chelator-induced ADAM10 production. Based on these results, we conclude that copper chelators regulate the balance between amyloidogenic and nonamyloidogenic processing of AßPP via promoting ADAM10 expression through MT1/2 /CREB-dependent signaling pathways.

Tetrathiomolybdate Treatment Leads to the Suppression of Inflammatory Responses through the TRAF6/NFκB Pathway in LPS-Stimulated BV-2 Microglia.

Although the positive relationship between copper and Alzheimer's disease (AD) was reported by a lot of epidemiological data, the mechanism is not completely known. Copper is a redox metal and serves as a mediator of inflammation. Because the homeostasis of copper is altered in Aß precursor protein (APP) and presenilin 1 (PS1) transgenic (Tg) mice, the using of copper chelators is a potential therapeutic strategy for AD. Here we report that a copper chelator, tetrathiomolybdate (TM), is a potential therapeutic drug of AD. We investigated whether TM treatment led to a decrease of pro-inflammatory cytokines in vivo and in vitro, and found that TM treatment reduced the expression of iNOS and TNF-α in APP/PS1 Tg mice through up-regulating superoxide dismutase 1 (SOD1) activity. In vitro, once stimulated, microglia secretes a variety of proinflammatory cytokines, so we utilized LPS-stimulated BV-2 cells as the inflammatory cell model to detect the anti-inflammatory effects of TM. Our results indicated that TM-pretreatment suppressed the ubiquitination of TRAF6 and the activation of NFκB without affecting the expression of TLR4 and Myd88 in vitro. By detecting the activity of SOD1 and the production of reactive oxygen species (ROS), we found that the anti-inflammatory effects of TM could be attributed to its ability to reduce the amount of intracellular bioavailable copper, and the production of ROS which is an activator of the TRAF6 auto-ubiquitination. Hence, our results revealed that TM-treatment could reduce the production of inflammatory cytokines by the suppression of ROS/TRAF6/AKT/NFκB signaling pathway.

Advances in biodegradable nanomaterials for photothermal therapy of cancer.

Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochemical properties of nanomaterials, various internal and external stimuli play key roles on nanomaterials uptake, transport, and clearance. In this review, we summarized novel nanoplatforms for photothermal therapy; these nanoplatforms can elicit stimuli-triggered degradation. We focused on the recent innovative designs endowed with biodegradable photothermal agents under different stimuli, including enzyme, pH, and near-infrared (NIR) laser.

An 18-mer Peptide Derived from Prosaposin Ameliorates the Effects of Aß1-42 Neurotoxicity on Hippocampal Neurogenesis and Memory Deficit in Mice.

The pathological hallmarks of Alzheimer's disease (AD) include amyloid-ß (Aß) accumulation, neurofibrillary tangle formation, synaptic dysfunction, and neuronal loss. The present study was performed to investigate the protective effects and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) on mice hippocampal progenitor cell proliferation, neurogenesis, and memory tasks after intracerebroventricular injection of Aß1-42 peptide. Seven days after Aß1-42 injection, significant proliferation of hippocampal progenitor cells and memory impairment were evident. Two weeks after Aß1-42 peptide injection, elevated numbers of surviving 5-bromo-2-deoxyuridine cells and newly formed neurons were detected. Treatment with PS18 attenuated these effects evoked by Aß1-42. Our data indicate that treatment with PS18 partially attenuated the increase in hippocampal neurogenesis caused by Aß1-42-induced neuroinflammation and prevented memory deficits associated with increased numbers of activated glial cells. We observed an increase in ADAM10 and decreases in BACE1, PS1/2, and AßPP protein levels, suggesting that PS18 enhances the nonamyloidogenic AßPP cleavage pathway. Importantly, our results further showed that PS18 activated the PI3K/Akt pathway, phosphorylated GSK-3α/ß, and, as a consequence, exerted a neuroprotective effect. In addition, PS18 showed a protective effect against Aß1-42-induced neurotoxicity via suppression of the caspase pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases, such as AD.

Deferoxamine-mediated up-regulation of HIF-1α prevents dopaminergic neuronal death via the activation of MAPK family proteins in MPTP-treated mice.

Accumulating evidence suggests that an abnormal accumulation of iron in the substantia nigra (SN) is one of the defining characteristics of Parkinson's disease (PD). Accordingly, the potential neuroprotection of Fe chelators is widely acknowledged for the treatment of PD. Although desferrioxamine (DFO), an iron chelator widely used in clinical settings, has been reported to improve motor deficits and dopaminergic neuronal survival in animal models of PD, DFO has poor penetration to cross the blood-brain barrier and elicits side effects. We evaluated whether an intranasal administration of DFO improves the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of dopaminergic neurons in the nigrostriatal axis and investigated the molecular mechanisms of intranasal DFO treatment in preventing MPTP-induced neurodegeneration. Treatment with DFO efficiently alleviated behavioral deficits, increased the survival of tyrosine hydroxylase (TH)-positive neurons, and decreased the action of astrocytes in the SN and striatum in an MPTP-induced PD mouse model. Interestingly, we found that DFO up-regulated the expression of HIF-1α protein, TH, vascular endothelial growth factor (VEGF), and growth associated protein 43 (GAP43) and down-regulated the expression of α-synuclein, divalent metal transporter with iron-responsive element (DMT1+IRE), and transferrin receptor (TFR). This was accompanied by a decrease in iron-positive cells in the SN and striatum of the DFO-treated group. We further revealed that DFO treatment significantly inhibited the MPTP-induced phosphorylation of the c-Jun N-terminal kinase (JNK) and differentially enhanced the phosphorylation of extracellular regulated protein kinases (ERK) and mitogen-activated protein kinase (MAPK)/P38 kinase. Additionally, the effects of DFO on increasing the Bcl-2/Bax ratio were further validated in vitro and in vivo. In SH-SY5Y cells, the DFO-mediated up-regulation of HIF-1α occurred via the activation of the ERK and P38MAPK signaling pathway. Collectively, the present data suggest that intranasal DFO treatment is effective in reversing MPTP-induced brain abnormalities and that HIF-1-pathway activation is a potential therapy target for the attenuation of neurodegeneration.

Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis.

Copper homeostasis is important for virulence of the fungus Cryptococcus neoformans, which can cause lethal meningoencephalitis in humans. Cryptococcus cells encounter high copper levels in the lung, where infection is initiated, and low copper levels in the brain. Here we demonstrate that two Cryptococcus copper transporters, Ctr1 and Ctr4, differentially influence fungal survival during pulmonary infection and the onset of meningoencephalitis. Protein Ctr1 is rapidly degraded under the high-copper conditions found in infected lungs, and its loss has no effect in fungal virulence in mice. By contrast, deleting CTR4 results in a hypervirulent phenotype. Overexpressing either Ctr1 or Ctr4 leads to profound reductions in fungal burden in the lung. However, during the onset of meningoencephalitis, expression of the copper transporters is induced and is critical for Cryptococcus virulence. Our work demonstrates that the fungal cells switch between copper detoxification and acquisition to address different copper stresses in the host.

Decrease in prosaposin in the Dystrophic mdx mouse brain.

BACKGROUND: Duchenne muscular dystrophy caused by a mutation in the X-linked dystrophin gene induces metabolic and structural disorders in the brain. A lack of dystrophin in brain structures is involved in impaired cognitive function. Prosaposin (PS), a neurotrophic factor, is abundant in the choroid plexus and various brain regions. We investigated whether PS serves as a link between dystrophin loss and gross and/or ultrastructural brain abnormalities. METHODOLOGY/PRINCIPAL FINDINGS: The distribution of PS in the brains of juvenile and adult mdx mice was investigated by immunochemistry, Western blotting, and in situ hybridization. Immunochemistry revealed lower levels of PS in the cytoplasm of neurons of the cerebral cortex, hippocampus, cerebellum, and choroid plexus in mdx mice. Western blotting confirmed that PS levels were lower in these brain regions in both juveniles and adults. Even with low PS production in the choroids plexus, there was no significant PS decrease in cerebrospinal fluid (CSF). In situ hybridization revealed that the primary form of PS mRNA in both normal and mdx mice was Pro+9, a secretory-type PS, and the hybridization signals for Pro+9 in the above-mentioned brain regions were weaker in mdx mice than in normal mice. We also investigated mitogen-activated protein kinase signalling. Stronger activation of ERK1/2 was observed in mdx mice, ERK1/2 activity was positively correlated with PS activity, and exogenous PS18 stimulated both p-ERK1/2 and PS in SH-SY5Y cells. CONCLUSIONS/SIGNIFICANCE: Low levels of PS and its receptors suggest the participation of PS in some pathological changes in the brains of mdx mice.

Prosaposin expression in the regenerated muscles of mdx and cardiotoxin-treated mice.

The trophic factor prosaposin (PS) is strongly expressed in skeletal muscle, and reportedly, a PS-derived peptide attenuates loss of muscle mass after nerve injury in vivo and increases myoblast fusion into myotubes in vitro. However, few studies have focused on the role of PS during muscle regeneration. We examined the expression of PS in the skeletal muscles in normal, mdx, and cardiotoxin (CTX)-treated mice using immunofluorescence staining, Western blotting, and in situ hybridisation. Immunofluorescence showed intense PS immunoreactivity in the peripheral cytoplasm of uninjured myofibres of normal mice and regenerated myofibres of 8 weeks post-CTX-injection mice. In early stage CTX-treated mice (14 days and earlier), intense PS immunoreactivity was also detected in the immune cells that infiltrated damaged muscle, but it was weak for regenerating myofibres. Western blot confirmed these findings. In contrast, PS was continuously low in mdx mice in both immunofluorescence and Western blotting. In situ hybridisation confirmed the decrease of PS mRNA in regenerated myofibres and revealed the main form of PS mRNA as Pro+0 without a 9-base insertion both in normal and mdx mice. The embryonic myosin (MYH3) was clearly localized in the newly regenerated myofibres at 3, 7, and 14 days of post-CTX-injection and mdx mice, but was lower in the late stage of regenerated myofibres (28 and 56 days post-CTX injection). The inverse distribution of MYH3 and PS indicates that the PS expression is closely related to the differentiation of regenerated myofibres. Investigation of the mitogen-activated protein (MAP) kinase signal pathway showed the inversely synchronous correlation of phosphorylated ERK1/2 with myofibre PS and the synchronous correlation of phosphorylated p-38 with myofibre PS. These data suggest that PS is involved in the regulation of muscle differentiation of regenerated fibres.

High-spin versus spin-crossover versus low-spin: geometry intervention in cooperativity in a 3D polymorphic iron(II)-tetrazole MOFs system.

Reported here are three 3D metal-organic framework (MOF) polymorphs with the chemical formula [Fe(2)(H(0.67)bdt)(3)]·xH(2)O (H(2)bdt = 5,5'-(1,4-phenylene)bis(1H-tetrazole)), all of which are constructed from similar Fe(II)-tetrazole rod secondary building units (SBUs) via covalent links, but exhibit diverse spin states regulated by inter-chain cooperativity.

Disruption of the CaMKII/CREB signaling is associated with zinc deficiency-induced learning and memory impairments.

Many studies have shown that zinc deficiency not only retards growth, but also affects several brain functions, including learning and memory. However, the underlying mechanism of impaired hippocampus-dependent learning and memory under zinc deficiency is poorly understood. In this study, young mice were fed a zinc-deficient diet (0.85 ppm) for 5 weeks. Morris water maze result showed that zinc deficiency results in spatial learning impairment. We then examined whether zinc depletion-induced learning and memory defects are associated with changes in signaling molecules essential for the expression of long-term potentiation. Immunoblot results showed that the protein levels of calmodulin (CaM), phosphorylated CaM-dependent protein kinase II (CaMKII), and phosphorylated cAMP-responsive element binding protein (CREB) were significantly reduced, whereas the total protein levels of CaMKII and CREB did not change in the zinc-deficient hippocampus. Thus, we provide a previously unrecognized mechanism whereby zinc deficiency impairs hippocampal learning and memory, at least in part, through disruption of the CaM/CaMKII/CREB signaling pathway.

Lactational zinc deficiency-induced hippocampal neuronal apoptosis by a BDNF-independent TrkB signaling pathway.

It is well-known that zinc deficiency leads to neuronal death in the brain. Here we tested the hypothesis that changes in the TrkB signaling pathway are involved in hippocampal neuronal apoptosis of suckling offspring with maternal zinc deficiency. Postpartum mice were fed a zinc-deficient (0.85 ppm) diet and their offspring were used as a lactational zinc deficiency mouse model. At P7, P14, and P21, changes in hippocampal neuronal apoptosis were assessed by Nissl and TUNEL staining. BDNF levels and TrkB neurotrophic signaling were examined using immunoblotting assay. Lactational zinc deficiency resulted in lower levels of p-TrkB and p-ERK, and higher levels of Bax/Bcl-2 and caspase-3 in the hippocampus, suggesting that zinc deficiency-induced low levels of TrkB phosphorylation would abrogate the downstream ERK signaling pathway, leading to hippocampal neuronal apoptosis. Most interestingly, our data showed that the activity of Src, a key molecule for zinc-induced TrkB activation through the BDNF-independent pathway, was inhibited significantly, and the expression levels of BDNF were significantly increased in the hippocampus of suckling mice. The present data indicate that zinc depletion-induced hippocampal neuronal apoptosis is likely through modulation of the TrkB neurotrophic signaling pathway by a BDNF-independent and Src-dependent mechanism, whereas higher expression of BDNF is considered as a protective response, which cannot fully compensate for the injury caused by maternal zinc deficiency.

[Effects of lipopolysaccharides of Bacterium prodigiosum on tumor growth and immunosuppression in mice].

OBJECTIVE: To observe the effects of lipopolysaccharides of Bacterium prodigiosum (BP-LPS) in inhibiting tumor growth and improving immunosuppression in mice. METHODS: In mice bearing S180 tumor and a mouse model of immunosuppression induced by cyclophosphamide (CTX), the tumor growth, indexes of the immune organs and peripheral white blood cell count were measured after intraperitoneal injection of BP-LPS. RESULTS: Injections of BP-LPS (40 U/kg) for 8 consecutive days resulted in a significant inhibition of the tumor growth in mice bearing S180 tumor (P<0.01), with a dose-dependent increase of the spleen indexes but no obvious changes in the thymus indexes. Intraperitoneal injections of BP-LPS for 7 days inhibited the reduction of peripheral white blood cells and spleen indexes in immunosuppressive mice, but did not produce any significant changes in normal mice. CONCLUSION: BP-LPS can inhibit the tumor growth in tumor-bearing mice and enhance the immune functions of immunosuppressive mice.

Zinc deficiency reduces neurogenesis accompanied by neuronal apoptosis through caspase-dependent and -independent signaling pathways.

Dietary zinc deficiency may affect zinc homeostasis in the brain and lead to reductions of neurogenesis and neuronal survival. However, the mechanisms responsible for the effects of zinc deficiency on hippocampal neurogenesis and neuronal death remain obscure. In the present study, young CD-1 mice were fed with zinc-deficient diet (0.85 ppm) for 5 weeks. The vesicular zinc was reduced at CA1 and CA3 regions of the hippocampus in zinc-deficient mice. The significant decreased zinc ions was associated with a reduction in proliferating cells labeled with bromo-deoxyuridine (BrdU) and immature neurons labeled with doublecortin (DCX) immunoreactivity in the dentate gyrus of the hippocampus. The processes of DCX-positive neurons were shortened, and flexuously went through into the granular cell layer in zinc-deficient hippocampus. There was also a conspicuous increase in the number of TUNEL-positive cells in the hippocampus after zinc-deficient diet treatment. Meanwhile, the apoptosis proteins, including Fas, Fas ligand (FasL), apoptosis inducing factor (AIF), and caspase-3, were significantly activated in zinc-deficient mouse hippocampus. These data suggest that chronic treatment with zinc-deficient diet results in reduction in hippocampal neurogenesis and increases neuronal apoptosis, indicating that zinc deficiency is associated with destroying structural plasticity in the hippocampus.

Golgi apparatus localization of ZNT7 in the mouse cerebellum.

We have recently reported that four members of the zinc transporter (ZNT) family, ZNT1, ZNT3, ZNT4, and ZNT6, are abundantly expressed in the mouse cerebellum. In the present study, we reported that ZNT7 was present throughout the cerebellar cortex. ZNT7 immunoreactivity was predominately present in the somas and primary dendrites of the Purkinje cells. ZNT7 was also present in the Bergmann glial cell bodies as well as their radial processes, which extended into the molecular cell layer. Confocal immunofluorescence results demonstrated that the expression of ZNT7 overlapped with that of TGN38 in the somas of the Purkinje cells and granule cells. Immuno-electron microscopic study showed that ZNT7 was localized to the membrane of the Golgi apparatus in the somas of the Purkinje cells, Bergmann glial cells, and granule cells. Western blot analysis demonstrated that a considerable amount of ZNT7 was expressed in the cerebellum. These findings suggest a significant role of ZNT7 in zinc homeostasis in the mouse cerebellum.

[Immunomodulatory effects of Fomes fomentarius polysaccharides: an experimental study in mice].

OBJECTIVE: To investigate the immunomodulatory effects of Fomes fomentarius polysaccharides (FFP) in mice. METHODS: MTT assay was employed to evaluate the in vitro metabolic activity of the mouse splenocytes treated with FFP at different concentrations, and the secretion of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma) and interleukin 2 (IL-2) from the cells were measured by enzyme-linked immunosorbent assay. The changes in the phagocytotic activity of mouse macrophage in response to FFP treatment were evaluated by phagocytosis percentage of chicken red blood cells (CRBCs). The effect of FFP on the humoral immunity was assessed in mice immunized with sheep red blood cells (SRBCs) by measuring the serum levels of specific antibody (hemolysin) against SRBCs. RESULTS: FFP at the concentrations of 25, 50, and 100 microg/ml all significantly enhanced the metabolic activity of mouse splenocytes in vitro and increased the production of TNF-alpha, IFN-gamma and IL-2. FFP treatment also markedly enhanced the metabolic activity of mouse peritoneal exudate cells and TNF-alpha production by the cells. At the doses of 25, 50, and 100 mg/kg, FFP significantly increased serum hemolysin level in mice immunized with SRBCs, and FFP at 50 and 100 mg/kg obviously increased the capacity of mouse peritoneal macrophages in vivo for CRBC phagocytosis. CONCLUSION: FFP can promote the secretion of TNF-alpha, IFN-gamma and IL-2 by mouse immunocytes and enhance mouse humoral immune response and the phagocytotic activity of the macrophages.

Expression of zinc transporter ZnT7 in mouse superior cervical ganglion.

The superior cervical ganglion (SCG) neurons contain a considerable amount of zinc ions, but little is known about the zinc homeostasis in the SCG. It is known that zinc transporter 7 (ZnT7, Slc30a7), a member of the Slc30 ZnT family, is involved in mobilizing zinc ions from the cytoplasm into the Golgi apparatus. In the present study, we examined the expression and localization of ZnT7 and labile zinc ions in the mouse SCG using immunohistochemistry, Western blot and in vivo zinc selenium autometallography (AMG). Our immunohistochemical analysis revealed that the ZnT7 immunoreactivity in the SCG neurons was predominately present in the perinuclear region of the neurons, suggesting an affiliation to the Golgi apparatus. The Western blot results verified that ZnT7 protein was expressed in the mouse SCGs. The AMG reaction product was shown to have a similar distribution as ZnT7 immunoreactivity. These observations support the notion that ZnT7 may participate in zinc transport, storage, and incorporation of zinc into zinc-binding proteins in the Golgi apparatus of mouse SCG neurons.