In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin / alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing.

Healing diabetic ulcers with chronic inflammation is a major challenge for researchers and professionals, necessitating new strategies. To rapidly treat diabetic wounds in rat models, we have fabricated a composite scaffold composed of alginate (Alg) and silk fibroin (SF) as a wound dressing that is laden with molecules of lithium chloride (LC). The physicochemical, bioactivity, and biocompatibility properties of Alg-SF-LC scaffolds were investigated in contrast to those of Alg, SF, and Alg-SF ones. Afterward, full-thickness wounds were ulcerated in diabetic rats in order to evaluate the capacity of LC-laden scaffolds to regenerate skin. The characterization findings demonstrated that the composite scaffolds possessed favorable antibacterial properties, cell compatibility, high swelling, controlled degradability, and good uniformity in the interconnected pore microstructure. Additionally, in terms of wound contraction, re-epithelialization, and angiogenesis improvement, LC-laden scaffolds revealed better performance in diabetic wound healing than the other groups. This research indicates that utilizing lithium chloride molecules loaded in biological materials supports the best diabetic ulcer regeneration in vivo, and produces a skin replacement with a cellular structure comparable to native skin.

From consumption to excretion: Lithium concentrations in honey bees (Apis mellifera) after lithium chloride application and time-dependent effects on Varroa destructor.

BACKGROUND: Owing to its systemic mode-of-action and ease of application, lithium chloride (LiCl) is an ideal varroacide for the control of Varroa destructor infestations in honey bee colonies. To better understand how LiCl functions within a colony, we screened different parts of honey bee anatomy for lithium accumulation. We wanted to elucidate the time-dependent effects of LiCl on V. destructor and its metabolism within honey bees when they were fed continuous LiCl treatments, as well as evaluate potential adverse effects such as accumulation in the hypopharyngeal glands of nurse bees, which could negatively impact queens and larvae. RESULTS: Cage experiments reveal rapid acaricidal onset, with >95% mite mortality within 48 h of treatment. Bee hemolymph analysis supports these observations, showing a rapid increase in lithium concentration within 12 h of treatment, followed by stabilization at a constant level. Lithium accumulates in the rectum of caged bees (≤475.5 mg kg-1 after 7 days of feeding 50 mm LiCl), reflecting the bees' metabolic and excretion process. Despite concerns about potential accumulation in hypopharyngeal glands, low lithium levels of only 0.52 mg kg-1 suggest minimal risk to the queen and 1st- and 2nd-instar larvae. Cessation of LiCl treatment results in a rapid decline in mite mortality in the first 5 days, which increases again thereafter, resulting in mite mortality of 77-90% after 10 days. CONCLUSION: These findings help optimize LiCl application in colonies to achieve high Varroa mortality without unwanted adverse effects and provide important baseline data for future registration. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Unlocking the Use of LiCl as an Inexpensive Salt for Lithium-Ion Batteries with a Novel Anion Receptor.

Lithium chloride (LiCl) is an inexpensive and environmentally friendly salt abundant in the ocean. However, the insolubility of LiCl in conventional electrolyte solvents prevents the practical use of LiCl for lithium-ion batteries. Here, we report a novel method to increase the solubility of LiCl in a conventional electrolyte. The solubility of LiCl in ethylene carbonate (EC)/dimethyl carbonate (DMC) (1/1, v/v) is about quadrupled by adding a small amount of anion receptor with two urea moieties as recognition sites connecting with an ether chain. Anion receptor is an organic molecule that can associate with anions. Our anion receptor is able to associate with chloride anion. The ionic conductivity of LiCl in EC/DMC increased from 0.023 mS cm-1 (without an anion receptor) to 0.075 mS cm-1 (with a 0.05 M anion receptor). The electrolyte in the presence of a 0.05 M receptor exhibits higher ionic conductivity, rate capability, and cyclability than the electrolyte without the receptor.

Uncovering the Therapeutic Potential of Lithium Chloride in Type 2 Diabetic Cardiomyopathy: Targeting Tau Hyperphosphorylation and TGF-ß Signaling via GSK-3ß Inhibition.

Diabetic cardiomyopathy (DCM) is a major complication of type 2 diabetes mellitus (T2DM) that leads to significant morbidity and mortality. The alteration in the signaling mechanism in diabetes leading to cardiomyopathy remains unclear. The purpose of this study is to investigate the role of tauopathy in myocardial dysfunction observed in T2DM. In that regard, diabetic Sprague Dawley rats were treated with intraperitoneal injections of lithium chloride (LiCl), inhibiting tau phosphorylation. Cardiac function was evaluated, and molecular markers of myocardial fibrosis and the TGF-ß signaling were analyzed. T2DM rats exhibited a decline in ejection fraction and fractional shortening that revealed cardiac function abnormalities and increased myocardial fibrosis. These changes were associated with tau hyperphosphorylation. Treating diabetic rats with LiCl attenuated cardiac fibrosis and improved myocardial function. Inhibition of GSK-3ß leads to the suppression of tau phosphorylation, which is associated with a decrease in TGF-ß expression and regulation of the pro-inflammatory markers, suggesting that tau hyperphosphorylation is parallelly associated with fibrosis and inflammation in the diabetic heart. Our findings provide evidence of a possible role of tau hyperphosphorylation in the pathogenesis of DCM through the activation of TGF-ß and by inducing inflammation. Targeting the inhibition of tau phosphorylation may offer novel therapeutic approaches to reduce DCM burden in T2DM patients.

Cadmium modulates intestinal Wnt/ß-catenin signaling ensuing intestinal barrier disruption and systemic inflammation.

The intricate architecture of the intestinal epithelium, crucial for nutrient absorption, is constantly threatened by environmental factors. The epithelium undergoes rapid turnover, which is essential for maintaining homeostasis, under the control of intestinal stem cells (ISCs). The central regulator, Wnt/ß-catenin signaling plays a key role in intestinal integrity and turnover. Despite its significance, the impact of environmental factors on this pathway has been largely overlooked. This study, for the first time, investigates the influence of Cd on the intestinal Wnt signaling pathway using a mouse model. In this study, male BALB/c mice were administered an environmentally relevant Cd dose (0.98 mg/kg) through oral gavage to investigate the intestinal disruption and Wnt signaling pathway. Various studies, including histopathology, immunohistochemistry, RT-PCR, western blotting, ELISA, intestinal permeability assay, and flow cytometry, were conducted to study Cd-induced changes in the intestine. The canonical Wnt signaling pathway experienced significant downregulation as a result of sub-chronic Cd exposure, which caused extensive damage throughout the small intestine. Increased intestinal permeability and a skewed immune response were also observed. To confirm that Wnt signaling downregulation is the key driver of Cd-induced gastrointestinal toxicity, mice were co-exposed to LiCl (a recognized Wnt activator) and Cd. The results clearly showed that the harmful effects of Cd could be reversed, which is strong evidence that Cd mostly damages the intestine through the Wnt/ß-catenin signalling axis. In conclusion, this research advances the current understanding of the role of Wnt/ß catenin signaling in gastrointestinal toxicity caused by diverse environmental pollutants.

Square-planar Tetranuclear Cluster-based Alkaline Earth Metal-organic Frameworks with Enhanced Proton Conductivity.

Alkaline earth (AE) metal complexes have garnered significant interest in various functional fields due to their nontoxicity, low density, and low cost. However, there is a lack of systematic investigation into the structural characteristics and physical properties of AE-metal-organic frameworks (MOFs). In this research, we synthesized isostructural MOFs consisting of AE4(µ4-Cl) clusters bridged by benzo-(1,2;3,4;5,6)-tris(thiophene-2'-carboxylic acid) (BTTC3-) ligands. The resulting structure forms a truncated octahedral cage denoted as [AE4(m4-Cl)]6(BTTC)8, which further linked to a porous three-dimensional framework. Among the investigated AE ions (Ca, Sr, and Ba), the Ca4-MOF demonstrated good chemical stability in water compared to Sr4-MOF and Ba4-MOF. The N2 adsorption and solid-state UV-vis-NIR absorption behaviors were evaluated for all AE4-MOFs, showing similar trends among the different metal ions. Additionally, the proton conduction study revealed that the Ca4-MOF exhibited ultra-high proton conductivity, reaching 3.52×10-2 S cm-1 at 343 K and 98 % RH. Notably, the introduction of LiCl via guest exchange resulted in an improved proton conduction of up to 6.36×10-2 S cm-1 under similar conditions in the modified LiCl@Ca4-MOF. The findings shed light on the regulation of physical properties and proton conductivity of AE-MOFs, providing valuable insights for their potential applications in various fields.

Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

RNA Isolation Method in Marginal Crops with High Agronomic Potential.

Ribonucleic Acid (RNA) isolation is a basic technique in the field of molecular biology. The purpose of RNA isolation is to acquire pure and complete RNA that can be used to evaluate gene expression. Many methods can be used to perform RNA isolation, all of them based on the chemical properties of nucleic acids. However, some of them do not achieve high RNA yields and purity levels when used in a number of marginally studied crops of agronomic importance, such as grain and vegetable amaranth plants. In the method described here, the use of guanidinium thiocyanate and two additional precipitation steps with different reagents designed to obtain high yields and RNA purity levels from diverse plant species employed for plant functional genomics studies is described.

Intrinsic Water Transport in Moisture-Capturing Hydrogels.

Moisture-capturing hydrogels have emerged as attractive sorbent materials capable of converting ambient humidity into liquid water. Recent works have demonstrated exceptional water capture capabilities of hydrogels while simultaneously exploring different strategies to accelerate water capture and release. However, on the material level, an understanding of the intrinsic transport properties of moisture-capturing hydrogels is currently missing, which hinders their rational design. In this work, we combine absorption and desorption experiments of macroscopic hydrogel samples in pure vapor with models of water diffusion in the hydrogels to demonstrate the first measurements of the intrinsic water diffusion coefficient in hydrogel-salt composites. Based on these insights, we pattern hydrogels with micropores to significantly decrease the required absorption and desorption times by 19% and 72%, respectively, while reducing the total water capacity of the hydrogel by only 4%. Thereby, we provide an effective strategy toward hydrogel material optimization, with a particular significance in pure-vapor environments.

Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin.

Ivermectin has broad-spectrum antiviral activities. Despite the failure in clinical application of COVID-19, it can serve as a lead compound for the development of more effective broad-spectrum antivirals, for which a better understanding of its antiviral mechanisms is essential. We thus searched for potential novel targets of ivermectin in host cells by label-free thermal proteomic profiling using Huh-7 cells. Inositol monophosphatase (IMPase) was found among the proteins with shifted thermal stability by ivermectin. Ivermectin could inhibit IMPase activity and reduce cellular myo-inositol and phosphatidylinositol-4-phosphate levels. On the other hand, inositol could impair the antiviral activity of ivermectin and lithium, an IMPase inhibitor with known antiviral activity. As phosphatidylinositol phosphate is crucial for the replication of many RNA viruses, inhibition of cellular myo-inositol biosynthesis may be an important antiviral mechanism of ivermectin. Hence, inhibition of IMPase could serve as a potential target for broad-spectrum antiviral development.

Silver-Assisted Hydrogen Evolution from Aluminum Oxidation in Saline Media.

A swarf of aluminum alloy with high corrosion resistance and ductility was successfully converted into fine hydro reactive powders via ball milling with silver powder and either lithium chloride or gallium. The latter substances significantly intensified particle size reduction, while silver formed 'cathodic' sites (Ag, Ag2Al), promoting Al corrosion in aqueous saline solutions with hydrogen generation. The diffraction patterns, microphotographs, and elemental analysis results demonstrated partial aluminum oxidation in the samples and their contamination with tungsten carbide from milling balls. Those factors were responsible for obtaining lower hydrogen yields than expected. For AlCl3 solution at 60 °C, Al-LiCl-Ag, Al-LiCl, Al-Ga-Ag, and Al-Ga composites delivered (84.6 ± 0.2), (86.8 ± 1.4), (80.2 ± 0.5), and (76.7 ± 0.7)% of the expected hydrogen, respectively. Modification with Ag promoted Al oxidation, thus providing higher hydrogen evolution rates. The samples with Ag were tested in a CaCl2 solution as well, for which the reaction proceeded much more slowly. At a higher temperature (80 °C) after 3 h of experiment, the corresponding hydrogen yields for Al-LiCl-Ag and Al-Ga-Ag powders were (46.7 ± 2.1) and (31.8 ± 1.9)%. The tested Ag-modified composite powders were considered promising for hydrogen generation and had the potential for further improvement to deliver higher hydrogen yields.

Isolation of Double-Stranded RNAs by Lithium Chloride Fractionation.

This procedure provides a comprehensive method for isolating double-stranded RNA (dsRNA) that relies on the different solubility of various nucleic acids in lithium chloride (LiC1). The approach offers several notable advantages including simplicity, avoidance of enzymatic treatments, and the ability to obtain relatively high yields of undegraded dsRNA over other conventional techniques. Moreover, it allows for the separation of different groups of cellular and viral nucleic acids from a single tissue sample. This method was further improved to increase the purity of dsRNA using plant tissues infected by RNA viruses.

Organocatalytic Lithium Chloride Oxidation by Covalent Organic Frameworks for Rechargeable Lithium-Chlorine Batteries.

Rechargeable Li-Cl2 battery is a promising high energy density battery system. However, reasonable cycle life could only be achieved under low specific capacities due to the sluggish oxidation of LiCl to Cl2 . Herein, we propose an amine-functionalized covalent organic framework (COF) with catalytic activity, namely COF-NH2 , that significantly decreases the oxidation barrier of LiCl and accelerates the oxidation kinetics of LiCl in Li-Cl2 cell. The resulting Li-Cl2 cell using COF-NH2 (Li-Cl2 @COF-NH2 ) simultaneously exhibits low overpotential, ultrahigh discharge capacity up to 3500 mAh/g and a promoted utilization ratio of deposited LiCl at the first cycle (UR-LiCl) of 81.4 %, which is one of the highest reported values to date. Furthermore, the Li-Cl2 @COF-NH2 cell could be stably cycled for over 200 cycles when operating at a capacity of 2000 mAh/g at -20 °C with a Coulombic efficiency (CE) of ≈100 % and a discharge plateau of 3.5 V. Our superior Li-Cl2 batteries enabled by organocatalyst enlighten an arena towards high-energy storage applications.

Deleterious effect of LiCl on honeybee (Aphis mellifera) grubs and no effect on Varroa mites (Varroa destructor) under normal beekeeping management.

A 2-year field experiment was performed to test lithium chloride, LiCl, application in a normal beekeeping management system. The effect of LiCl on bee larval mortality, beehive weight (honey production) and Varroa mite mortality were tested. Spectrometric quantification of Li on honey and the larval body were made to test the effectiveness of the presence of LiCl. Li was detected in bee larval bodies and in honey over 2 years, from 2018 to 2019. According to the results, no effect of LiCl on mite mortality or bee larval mortality was detected in the first year of application. By assessing the weight variation of beehives, only one LiCl-treated hive showed a significantly higher weight, whereas no other differences were detected between treatments and control. The same trend seen in 2018 was repeated in 2019, while a total bee larval mortality was observed after the first LiCl application, and still no differences in Varroa mite mortality were observed. According to these results, it was concluded that LiCl has no effect on Varroa mite mortality during normal beekeeping practice; furthermore, the recommended amount of treatment (25 mM) had a lethal effect (i.e., total mortality) on larvae following repeated applications.

Lithium chloride treatments in free flying honey bee colonies: efficacy, brood survival, and within-colony distribution.

The efficacy of various lithium chloride (LiCl) applications in eradicating the parasitic mite Varroa destructor in honey bee colonies was investigated, with a specific focus on its impact on brood development. In broodless colonies (3 weeks post queen caging), the highest efficacy of 98% was achieved with a 9-day treatment of 2.5 kg of candy spiked with 50 mM LiCl. A shorter 5-day treatment with 2 kg of 50 mM LiCl candy resulted in an efficacy of 78%. In colonies with brood, a repeated short-term application of 4 × 0.5 kg 50 mM LiCl candy yielded an efficacy of 88%. LiCl treatment led to a removal of the first batch of brood reared after release of the queen. However, no long-term effects on colony growth were observed, and the colonies successfully overwintered. Additionally, the study demonstrated that lithium is rapidly distributed among the bees of a colony within 2 days, yet only low concentrations were detected in stored food samples. This suggests that the bees efficiently absorb and distribute lithium within the colony. The harvested honey in the following spring revealed a lithium concentration of 0.1-0.2 mg/kg, which is below naturally occurring lithium levels in honey. Based on these findings, LiCl can be considered an effective and easy-to-apply acaricide in broodless colonies, and even in colonies with brood, it had good efficacy and no long-term effects on colony survival. Further research may be necessary to determine the optimal treatment period for achieving an efficacy over 95%.

Involvement of Glycogen Synthase Kinase 3ß (GSK3ß) in Formation of Phosphorylated Tau and Death of Retinal Ganglion Cells of Rats Caused by Optic Nerve Crush.

Tauopathy is a neurodegenerative condition associated with oligomeric tau formation through abnormal phosphorylation. We previously showed that tauopathy is involved in death of retinal ganglion cells (RGCs) after optic nerve crush (ONC). It has been proposed that glycogen synthase kinase 3ß (GSK3ß) is involved in the hyperphosphorylation of tau in Alzheimer's disease. To determine the roles of GSK3ß in tauopathy-related death of RGCs, lithium chloride (LiCl), a GSK3ß inhibitor, was injected intravitreally just after ONC. The neuroprotective effects of LiCl were determined by counting Tuj-1-stained RGCs on day 7. Changes of phosphorylated (ser 396) tau in the retina were determined by Simple Western analysis (WES) on day 3. Retinal GSK3ß levels were determined by immunohistochemistry (IHC) and an ELISA. There was a 1.9- and 2.1-fold increase in the levels of phosphorylated tau monomers and dimers on day 3 after ONC. LiCl significantly suppressed the increase in the levels of phosphorylated tau induced by ONC. GSK3ß was mainly present in somas of RGCs, and ELISA showed that retinal levels increased to 2.0-fold on day 7. IHC showed that the GSK3ß expression increased over time and remained in RGCs that were poorly stained by Tuj-1. The GSK3ß and tau expression was colocalized in RGCs. The number of RGCs decreased from 1881 ± 188 (sham control) to 1150 ± 192 cells/mm2 on day 7, and LiCl preserved the levels at 1548 ± 173 cells/mm2. Accordingly, GSK3ß may be a promising target for some optic nerve injuries.

Downregulating NHE-1 decreases the apoptosis of hippocampal cells in epileptic model rats based on the NHE-1/calpain1 pathway.

Seizure is associated with pathological changes of hippocampus, but the mechanism by which hippocampal neuronal apoptosis promotes epilepsy is unclear. Our previous study showed that the expression of NHE-1 was increased in epileptic model rats. Therefore, this study further explores the effect of NHE-1 on hippocampal cells apoptosis and seizure in lithium chloride-pilocarpine epileptic model rats. First, we established a lithium chloride-pilocarpine induced epileptic rat model and detected the expression of NHE-1, calpain1 and apoptosis in the hippocampus. Then, we further down-regulated NHE-1 to observe the expression of calpain1 and apoptosis in the hippocampus, as well as its effect on seizures in rats. We found that the expression of NHE-1 and calpain1 and apoptosis in the hippocampus was significant increased in the model group. After down-regulating NHE-1, the expression of calpain1 was decreased, and hippocampal cell apoptosis was alleviated. In addition, down-regulation of NHE-1 reduced the frequency and duration of seizures in epileptic rats. Therefore, hippocampal NHE-1 overexpression is closely related to the development of neuronal apoptosis in a rat model of epilepsy, and downregulating NHE-1 expression can reduce cell apoptosis. Moreover, the NHE-1/calpain1 signaling pathway may be an important mechanism leading to hippocampal cell apoptosis.

Facile and efficient chitosan-based hygroscopic aerogel for air dehumidification.

Sorption dehumidification, as an energy-saving and eco-friendly approach, has been emerging in application for air dehumidification. Here, a prospective method is proposed to prepare biomass-based hygroscopic aerogels that are easily applicable, sustainable, high-efficient, and recyclable. The chitosan-based aerogel with a porous and hydrophilic network acts as the carrier and water reservoir for the uniformly distributed lithium chloride hygroscopic salt, and provides the hygroscopic salt with more liberal water channels to facilitate moisture capture and transfer. As a consequence, the prepared chitosan/polyvinyl alcohol@lithium chloride (chitosan/PVA@LiCl) hygroscopic aerogel exhibits an excellent moisture absorption capacity of up to 2.77 g g-1 at a relative humidity of 90 %. Meanwhile, as the chitosan/PVA@LiCl aerogel is set in a closed space about 2200 times larger than its own volume, the relative humidity can be reduced from 90 % to 32 % within 2 h, and further lower to 25 % after 4 h. Furthermore, combined with multi-walled carbon nanotubes, the photothermal hygroscopic aerogel is obtained that can rapidly desorb water under sunlight, thus to realize energy-free cycle. Overall, the renewable biomass-based aerogel materials with the advantages of simple preparation and excellent hygroscopic performance provides a new path for the development of sorption dehumidification technology.

Lithium chloride promotes diabetic corneal epithelial wound healing by activating the Wnt/ß­catenin signaling pathway.

Corneal epithelial abnormality is a common manifestation of diabetic keratopathy and leads to delayed epithelial wound healing. The Wnt/ß-catenin signaling pathway participates in the development, differentiation and stratification of corneal epithelial cells. The present study compared the expression of Wnt/ß-catenin signaling pathway related factors, including Wnt7a, ß-catenin, cyclin D1 and phosphorylated (p-) glycogen synthase kinase 3 ß (Gsk3b) between normal and diabetic mouse corneas, by reverse transcription-quantitative PCR, western blotting and immunofluorescence staining. It was found that the expression of the Wnt/ß-catenin signaling pathway related factors was downregulated in diabetic corneas. Upon corneal epithelium scraping, the wound healing rate was significantly increased in diabetic mice after topical treatment with lithium chloride. After further investigation, significantly upregulated levels of Wnt7a, ß-catenin, cyclin D1 and p-Gsk3b were found in the diabetic group 24 h after treatment, accompanied by ß-catenin nuclear translocation observed by immunofluorescence staining. These results suggest that active Wnt/ß-catenin pathway can promote diabetic corneal epithelial wound healing.

Cytomegalovirus infection induces Alzheimer's disease-associated alterations in tau.

Alzheimer's disease (AD) manifests with loss of neurons correlated with intercellular deposition of amyloid (amyloid plaques) and intracellular neurofibrillary tangles of hyperphosphorylated tau. However, targeting AD hallmarks has not as yet led to development of an effective treatment despite numerous clinical trials. A better understanding of the early stages of neurodegeneration may lead to development of more effective treatments. One underexplored area is the clinical correlation between infection with herpesviruses and increased risk of AD. We hypothesized that similar to work performed with herpes simplex virus 1 (HSV1), infection with the cytomegalovirus (CMV) herpesvirus increases levels and phosphorylation of tau, similar to AD tauopathy. We used murine CMV (MCMV) to infect mouse fibroblasts and rat neuronal cells to test our hypothesis. MCMV infection increased steady-state levels of primarily high molecular weight forms of tau and altered the patterns of tau phosphorylation. Both changes required viral late gene products. Glycogen synthase kinase 3 beta (GSK3ß) was upregulated in the HSVI model, but inhibition with lithium chloride suggested that this enzyme is unlikely to be involved in MCMV infection mediated tau phosphorylation. Thus, we confirm that MCMV, a beta herpes virus, like alpha herpes viruses (e.g., HSV1), can promote tau pathology. This suggests that CMV infection can be useful as another model system to study mechanisms leading to neurodegeneration. Since MCMV infects both mice and rats as permissive hosts, our findings from tissue culture can likely be applied to a variety of AD models to study development of abnormal tau pathology.