Iron Recycle-Driven Organic Capture and Sidestream Anaerobic Membrane Bioreactor for Revolutionizing Bioenergy Generation in Municipal Wastewater Treatment.

The practicality of intensifying organic matter capture for bioenergy recovery to achieve energy-neutral municipal wastewater treatment is hindered by the lack of sustainable methods. This study developed innovative processes integrating iron recycle-driven organic capture with a sidestream anaerobic membrane bioreactor (AnMBR). Iron-assisted chemically enhanced primary treatment achieved elemental redirection with 75.2% of chemical oxygen demand (COD), 20.2% of nitrogen, and 97.4% of phosphorus captured into the sidestream process as iron-enhanced primary sludge (Fe-PS). A stable and efficient biomethanation of Fe-PS was obtained in AnMBR with a high methane yield of 224 mL/g COD. Consequently, 64.1% of the COD in Fe-PS and 48.2% of the COD in municipal wastewater were converted into bioenergy. The acidification of anaerobically digested sludge at pH = 2 achieved a high iron release efficiency of 96.1% and a sludge reduction of 29.3% in total suspended solids. Ultimately, 87.4% of iron was recycled for coagulant reuse, resulting in a theoretical 70% reduction in chemical costs. The novel system evaluation exhibited a 75.2% improvement in bioenergy recovery and an 83.3% enhancement in net energy compared to the conventional system (primary sedimentation and anaerobic digestion). This self-reliant and novel process can be applied in municipal wastewater treatment to advance energy neutrality at a lower cost.

A dual functional tunable terahertz metamaterial absorber based on vanadium dioxide.

A dual-functional switchable metamaterial absorber (MMA) based on vanadium dioxide (VO2), which achieves flexible switching between broadband absorption and four-band absorption by adjusting the VO2 conductivity, was proposed. The device has a broadband absorption function when VO2 is in the metal phase, and the conductivity is 3 × 105 S m-1. Numerical simulation shows that the absorption rate of the device reaches over 90% in the frequency range of 3.36-6.98 THz. The absorber exhibits polarization insensitivity and wide-angle absorption to transverse electric (TE) and transverse magnetic (TM) waves. When VO2 is in the insulator phase, and the conductivity is 3 × 102 S m-1, the device switches to a narrowband absorber with a band-efficient absorption function. Numerical simulation shows that the device has an absorption rate of 99.7% at 2.39 THz, 98.3% at 2.83 THz, 95.6% at 3.84 THz, and 96.1% at 4.61 THz. It can be used as a sensor with high sensitivity. In addition, to verify the absorption mechanism of the absorber, we introduced impedance matching theory to analyze the device. Finally, the influence of structural parameters on the performance of resonators was investigated. Through the joint action of multi-layer structures, the proposed MMA concentrates broadband and narrowband absorption functions on one device, achieving flexible switching between tasks without changing the structure. The switchable metamaterial absorber designed through simple tuning methods has broad application prospects in stealth technology and thermal emitters. It provides a wide range of ideas for the design of terahertz functional devices.

Focal length switchable metalens based on vanadium dioxide.

A metalens is a flat lens that can control the phase of light so that dispersed light can be reconcentrated. This study devised a tunable metalens with a switchable focal length based on the phase transition properties of vanadium dioxide (V O 2). The unit structure comprises three layers from bottom to top: gold, polyimide, and two square resonant rings. The metalens can not only transform incident x-polarized waves into y-polarized waves but also achieve beam focusing simultaneously. The designed metalens achieves polarization conversion efficiency at an operating frequency of 0.8 THz. In the insulating state of V O 2, the beam focal point is at L=1914µm; in the metallic state, the wave converges at L=982µm, closely aligning with the predetermined focal length. By controlling external temperature, focal point switching can be achieved, making it highly versatile in practical applications.

Cyanine-Anchored Silica Nanochannels for Light-Driven Synergistic Thermo-Chemotherapy.

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light-responsive nanoparticles that can maximize the potency of synergistic thermo-chemotherapy under light irradiation. Here, spatially confined cyanine-anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS-DOX-NCs) for light-driven synergistic cancer therapy are introduced. CS-DOX-NCs possess a J-type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π-π interaction with cyanine dye. Under near-infrared light irradiation, CS-DOX-NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J-type Cypate aggregates, trigger the light-driven drug release through the destabilization of temperature-sensitive π-π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species-mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS-DOX-NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light-driven nanoparticles for synergistic cancer therapy.

Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4.

In recent years, mGlu4 has received great research attention because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson's disease (PD). A specific mGlu4 PET radioligand could be an important tool in understanding the role of mGlu4 in both healthy and disease conditions, and also for the development of new drugs. In this study, we synthesized four new N-(methylthiophenyl)picolinamide derivatives 11-14. Of these ligands, 11 and 14 showed high in vitro binding affinity for mGlu4 with IC50 values of 3.4nM and 3.1nM, respectively, and suitable physicochemical parameters. Compound 11 also showed enhanced metabolic stability and good selectivity to other mGluRs. [(11)C]11 and [(11)C]14 were radiolabeled using the [(11)C]methylation of the thiophenol precursors 20a and 20c with [(11)C]CH3I in 19.0% and 34.8% radiochemical yields (RCY), and their specific activities at the end of synthesis (EOS) were 496±138GBq/µmol (n=6) and 463±263GBq/µmol (n=4), respectively. The PET studies showed that [(11)C]11 accumulated fast into the brain and had higher uptake, slower washout and 25% better contrast than [(11)C]2, indicating improved imaging characteristics as PET radiotracer for mGlu4 compared to [(11)C]2. Therefore, [(11)C]11 will be a useful radioligand to investigate mGlu4 in different biological applications.

PET imaging studies show enhanced expression of mGluR5 and inflammatory response during progressive degeneration in ALS mouse model expressing SOD1-G93A gene.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disorder. Genetic studies have linked mutation of the gene SOD1 to ALS pathology as well as several other pathological processes including modulation of glutamatergic function and inflammatory processes. Since therapeutic approaches for ALS are focused on glutamatergic function, we investigated modulation of glutamate transport based on its receptor function as well as excitotoxicity-induced inflammatory response. METHODS: In vivo positron emission tomography (PET) imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) using [(18)F]FPEB ([(18)F]3-fluoro-5-(2-pyridylethynyl)benzonitrile) and inflammatory response using [(11)C]PBR28 (peripheral benzodiazepine receptor ligand 28) were done in an early and a late phase of neurodegeneration in four ALS mice expressing SOD1-G93A gene and four control base mice (C57/BL6). Accumulation of [(18)F]FPEB and [(11)C]PBR28 were quantitated in several brain areas and spinal cord to determine degeneration-induced modulation. The studies were completed with immunohistochemical analyses of mGluR5 and inflammatory response. RESULTS: These studies showed enhanced binding potential of [(18)F]FPEB in several brain areas including striatum, hippocampus, and frontal cortex. In the whole brain, the binding potential increased 49 ± 9 % from base mice to ALS-type mice and further enhanced 23 ± 4 % during disease progression. Also, in the spinal cord 6-22 %, enhanced accumulation of [(18)F]FPEB was observed during progression of the disease. The accumulation of [(11)C]PBR28 increased by 110 ± 33 % in the whole brain during progression of the disease indicating significant inflammatory process. [(11)C]PBR28 accumulation enhanced 89-264 % in the spinal cord and 204 % in the lungs. The end point immunohistochemical analyses verified the enhanced mGluR5 expression and inflammation. CONCLUSIONS: These results confirm the role of glutamate and inflammation in ALS-type pathology. These data also support the hypothesis that excessive glutamate may contribute to inflammation in the chronic neurodegenerative processes in ALS.

Proteomics and phosphoproteomics analysis identifies liver immune protein markers in large yellow croakers (Larimichthys crocea) fed a soybean oil-based diet.

Dietary fish oil (FO) replacement has led to an inflammatory response in fish species. This study aimed to identify immune-related proteins in the liver tissue of fish fed a FO-based or soybean oil (SO)-based diet. By conducting proteomics and phosphoproteomics analyses, a total of 1601 differentially expressed proteins (DEPs) and 460 differentially abundant phosphorylated proteins (DAPs) were identified, respectively. Enrichment analysis revealed immune-related proteins involved in bacterial infection, pathogen identification, cytokine production, and cell chemotaxis. The mitogen-activated protein kinase (MAPK) pathway exhibited significant alterations in both protein and phosphorylation levels, with several hub DEPs and DAPs associated with MAPK pathway and leukocyte transendothelial migration being notable. In vitro experiments indicated that linolenic acid (LNA), derived from SO, inhibited the expression of NF-E2-related factor 2 (Nrf2), but increased the expression of signaling proteins linked to nuclear factor κB (NF-κB) and MAPK pathways. Transwell assays indicated that treatment of liver cells with LNA promoted macrophage migration. Collectively, the results showed that the SO-based diet upregulated the expression of NF-κB signaling-related proteins and activated the MAPK pathway, promoting immune cell migration. These findings provide novel insights for developing effective solutions to alleviate health problems caused by dietary high levels of SO inclusion.

Enhanced digestion of sludge via co-digestion with food waste in a high-solid anaerobic membrane bioreactor: Performance evaluation and microbial response.

A 15 L high-solid mesophilic AnMBR was operated for the digestion of food waste, primary sludge and excess sludge. The digestion performance was evaluated from the perspective of methane generation, permeate quality and organic reduction. Furthermore, the change in the microbial community was investigated by 16S rRNA gene analysis. The results showed that the introduction of sludge decreased the H2S levels in biogas compared with the mono-digestion of food waste and the co-digestion with food waste increased biogas and methane production compared with the mono-digestion of sludge. A substitution ratio of 25 % became a turning point of permeate composition and reaction rates. The energy recovery ratios of the mesophilic AnMBR were over 75 % based on stoichiometric analysis. In reaction kinetics analysis, hydrolysis as the first step of anaerobic digestion was found to be most influenced by the composition of the substrate. Finally, the microbial community structures were stable under tested conditions while the evolutionary relationships within the dominant phyla were observed. In the archaea community, Methanosaeta was the dominant methanogen regardless sludge ratio in the substrate.

Methanogenic treatment of dairy product wastewater by thermophilic anaerobic membrane bioreactor: Ammonia inhibition and microbial community.

Dairy product wastewater contains high-strength organic matter suitable for anaerobic treatment, but excessive protein degradation may lead to an ammonia inhibition problem. This work studied protein-rich dairy product wastewater treatment in the anaerobic membrane bioreactor. The results showed that a temporary self-detoxification phase of ammonia inhibition from the change of pH buffer system was vital for rapid reactor recovery by substrate dilution. The ammonia washout from the reactor was simulated by a kinetic model. After ammonia inhibition, the relative abundance of syntrophic lactic and propionic acids oxidising bacteria significantly reduced along with fermentative bacteria involved in mixed organic acids production. Nevertheless, the relative abundance of the protein degradation bacteria producing acetic acid and H2/CO2 increased. A potential metabolic process change was proposed by profiling the functional community. To conclude, substrate dilution is essential for overcoming ammonia inhibition in the anaerobic treatment of protein-rich dairy product wastewater.

Characterization of trace metal impact on organic acid metabolism and functional microbial community in treating dairy processing wastewater with thermophilic anaerobic membrane bioreactor.

The anaerobic digestion (AD) of dairy processing wastewater (DPW) to produce bioenergy is considered promising but also associated with the possibility of an unbalanced organic matter and trace metal (TM) content. In this study, the TM content and its impact on AD were determined in an anaerobic membrane bioreactor operated to treat DPW. The results indicated that a deficiency in TMs resulted in the slow deterioration of the process, reducing biogas production, disrupting the buffer system, and the massive accumulation of organic acid. The deficiency of Co/Ni was significant, while iron fluctuated due to microbial and chemical effects. Syntrophic propionate oxidizing bacteria and methanogen were the main groups suppressed under the TM deficient environment, resulting in AD failure. No inhibitory effect on the lactic acid metabolism was observed. Hence, supplying theoretical TM dosage to DPW was necessary to realize the efficient and stable AD process and robust microbial community.

Effects of meteorological factors and groundwater depths on plant sap flow velocities in karst critical zone.

Determining water supply intensity of fracture/conduits is one of the difficulties involved in the research of plant transpiration water consumption in the Karst Critical Zone (KCZ). Our aims were to evaluate the effect of groundwater depth on plant sap flow velocities in KCZ. Thus, four sampled plots with different groundwater depth (GD) in boreholes KCZ7 (4 to 10 m GD), KCZ5 (2 to 9 m GD), KCZ1 (0 to 8 m GD) and KCZ3 (2 to 5 m GD), were selected, and the plant stem sap flow velocity in each plot were also monitored continuously and automatically using heat ratio techniques. The daily sap flow flux of Toona sinensis varied between 0.35 kg d-1 in KCZ3 and 1.50 kg d-1 in KCZ1. Photosynthetically active radiation (PAR), vapor pressure deficit (VPD), and gust velocity (ZWS) were the primary meteorological factors that determined the sap flow velocity of T. sinensis, which contributed to a regression equation, while the influence of GD on sap flow was complex. Most of the sap flow velocity had no obvious significant correlation with the GD; however, the sap flow velocity in four different GD showed significant differences (P < 0.05). Unit sap flow velocity changes induced by unit GD changes (Kv) in KCZ7 and KCZ1 samples was faster than that of other samples. In brief, the sap flow velocity was mainly affected by the PAR and VPD in KCZ7, KCZ5 and KCZ1 because of the sufficient epikarst water, while the sap flow velocity in KCZ3 was mainly affected by the rock water content. The karst aquifer medium and GD was the main factors causing the difference sap flow velocity in the four sample plots. This finding indicated that KCZ aquifer medium structure may have an important influence on plant water utilization.

Characterization of biogas production and microbial community in thermophilic anaerobic co-digestion of sewage sludge and paper waste.

To recover the biogas from sewage sludge and paper waste (PW), the methanogenic performance of thermophilic anaerobic co-digestion of sewage sludge with PW was assessed by a continuous experiment. The effects on the biogas production and microbial community were investigated by changing the PW ratio from 0 to 66.7%. The optimal performance was obtained at the ratio of sewage sludge: PW = 4:6 (total solids), where the COD removal efficiency and biogas production increased from 58.34±5.90% to 72.92±0.08% and 438±53 to 594±72 mL/g-VSadded, respectively. By investigating the trend of carbohydrate and protein degradation rates, the competition between carbohydrate and protein degradation was quantified. The critical PW addition ratio was about (63.64%), where the protein degradation rate decreased to zero with increasing PW addition. Meanwhile, the microbial analysis showed that cellulolytic bacteria outcompeted proteolytic bacteria and to be the predominant group after PW addition.

Methanogenic performance and microbial community during thermophilic digestion of food waste and sewage sludge in a high-solid anaerobic membrane bioreactor.

The methanogenic performance and microbial community of the thermophilic anaerobic mono-digestion and co-digestion of food waste and sewage sludge in a high-solid membrane bioreactor were investigated by a continuous experiment. The methane recovery rate of the system reached 98.0% and 89.0% when the substrate was pure food waste and 25% sewage sludge substitution, respectively. Kinetics characterization showed that hydrolysis was the rate-limiting step in both mono-digestion and co-digestion while methanogenic performance and microbial community were significantly affected by feed condition. The dominant archaea for methane generation shifted from Methanothermobacter thermophilus (72.82%) to Methanosarcina thermophila (96.25%) with sewage sludge gradually added from 0% to 100% in the substrate. The relationships between digestion performance, such as the accumulation of soluble proteins in the reactor, and functional microbial groups were also carefully analyzed. Finally, reasonable metabolic pathways for mono-digestion and co-digestion were summarized.

Political optimizer with interpolation strategy for global optimization.

Political optimizer (PO) is a relatively state-of-the-art meta-heuristic optimization technique for global optimization problems, as well as real-world engineering optimization, which mimics the multi-staged process of politics in human society. However, due to a greedy strategy during the election phase, and an inappropriate balance of global exploration and local exploitation during the party switching stage, it suffers from stagnation in local optima with a low convergence accuracy. To overcome such drawbacks, a sequence of novel PO variants were proposed by integrating PO with Quadratic Interpolation, Advance Quadratic Interpolation, Cubic Interpolation, Lagrange Interpolation, Newton Interpolation, and Refraction Learning (RL). The main contributions of this work are listed as follows. (1) The interpolation strategy was adopted to help the current global optima jump out of local optima. (2) Specifically, RL was integrated into PO to improve the diversity of the population. (3) To improve the ability of balancing exploration and exploitation during the party switching stage, a logistic model was proposed to maintain a good balance. To the best of our knowledge, PO combined with the interpolation strategy and RL was proposed here for the first time. The performance of the best PO variant was evaluated by 19 widely used benchmark functions and 30 test functions from the IEEE CEC 2014. Experimental results revealed the superior performance of the proposed algorithm in terms of exploration capacity.

Temperature-phased anaerobic co-digestion of food waste and paper waste with and without recirculation: Biogas production and microbial structure.

Two temperature-phased anaerobic digestion (TPAD) systems (55 °C in the first reactor and 35 °C in the second reactor) with and without recirculation were operated in parallel for the co-digestion of food waste and paper waste. A long-term experiment was carried out for these two systems with the paper waste ratios elevated from 0 to 50%. The removal efficiencies of COD, TS, VS, carbohydrate and protein in the recirculated TPAD system were higher than those of the non-recirculated system. The successful acclimation of thermophilic cellulose-degrading bacteria in the first reactor (RT1), partly due to recirculation, ensured the effective degradation of cellulose when the paper waste ratio was higher than 40%, resulting in the production of large amounts of hydrogen in reactor RT1. In the absence of recirculation, the main substance produced in the first reactor of the non-recirculated system (T1) was lactic acid. This gradually led to over-acidification and a low degradation efficiency and no methane or hydrogen was produced in T1. Recirculation helped to establish a stable bacterial community capable of producing bio-hydrogen in reactor RT1. The relatively low pH of 5.5 in the RT1 inhibited the activity of hydrogenotrophic archaea without consuming hydrogen, facilitating high hydrogen production levels.

Synthesis and Characterization of Fluorine-18-Labeled N-(4-Chloro-3-((fluoromethyl-d2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain.

We have synthesized and characterized [18F]-N-(4-chloro-3-((fluoromethyl-d2)thio)phenyl)-picolinamide ([18F]15) as a potential ligand for the positron emission tomography (PET) imaging of mGluR4 in the brain. Radioligand [18F]15 displays central nervous system drug-like properties, including mGluR4 affinity, potent mGluR4 PAM activity, and selectivity against other mGluRs, as well as sufficient metabolic stability. Radiosynthesis was carried out in two steps. The radiochemical yield of [18F]15 was 11.6 ± 2.9% (n = 7, decay corrected) with a purity of 99% and a molar activity of 84.1 ± 11.8 GBq/µmol. Ex vivo biodistribution studies showed reversible binding of [18F]15 in all investigated tissues including the brain, liver, heart, lungs, and kidneys. PET imaging studies in male Sprague Dawley rats showed that [18F]15 accumulates in the brain regions known to express mGluR4. Pretreatment with the unlabeled mGluR4 PAM compounds 13 (methylthio analogue) and 15 showed significant dose-dependent blocking effects. These results suggest that [18F]15 is a promising radioligand for PET imaging mGluR4 in the brain.

Positron emission tomography of herpes simplex virus 1 oncolysis.

Viral oncolysis, the destruction of cancer cells by replicating viruses, is under clinical investigation for cancer therapy. Lytic viral replication in cancer cells both destroys the cells and liberates progeny virion to infect adjacent cancer cells. The safety and efficacy of this approach are dependent on selective and robust viral replication in cancer cells rather than in normal cells. Methods to detect and quantify viral replication in tissues have relied on organ sampling for molecular analyses. Preclinical and clinical studies of viral oncolysis will benefit significantly from development of a noninvasive method to repetitively measure viral replication. We have shown that positron emission tomography (PET) allows for in vivo detection of herpes simplex virus (HSV)-1 replication in tumor cells using 9-(4-[(18)F]-fluoro-3-[hydroxymethyl]butyl)guanine ([(18)F]FHBG) as the substrate for HSV thymidine kinase (HSV-TK). As expected, phosphorylated [(18)F]FHBG is initially trapped within HSV-1-infected tumor cells and is detectable as early as 2 h following virus administration. MicroPET images reveal that [(18)F]FHBG accumulation in HSV-1-infected tumors peaks at 6 h. However, despite progressive accumulation of HSV-1 titers and HSV-TK protein in the tumor as viral oncolysis proceeds, tumor cell degradation resulting from viral oncolysis increases over time, which limits intracellular retention of [(18)F]FHBG. These observations have important consequences with regard to strategies to use [(18)F]FHBG PET for monitoring sites of HSV-TK expression during viral oncolysis.

Targeting of NT5E by miR-30b and miR-340 attenuates proliferation, invasion and migration of gallbladder carcinoma.

MicroRNAs (miRNAs) have been closely associated with the proliferation, invasion and migration of various cancers, including gallbladder carcinoma (GBC). Previous studies have revealed dysregulation of miR-30b and miR-340 in many types of cancer. However, the role of miR-30b and miR-340 in the development and progression of GBC remains unclear. Moreover, epithelial-to-mesenchymal transition (EMT) has been gradually viewed as a significant contributor to tumor metastasis. In this study, the cell line GBC-SD was used and we explored that EMT promoted GBC cells invasion and migration and inhibited the expression level of miR-30b and miR-340 compared with the control. We showed that overexpression of miR-30b and miR-340 suppressed GBC cells proliferation, invasion and migration, as well as the expression of EMT-associated genes. In addition, we identified ecto-5'-nucleotidase (NT5E) as a common target of miR-30b and miR-340 using bioinformatics analysis and a luciferase assay. Further experiments found that exogenous expression of NT5E in GBC cells could partially reverse the inhibitory effect of miR-30b and miR-340 on cell proliferation, invasion and migration. Our findings suggest that NT5E-targeting miRNAs (miR-30b and miR-340) function as tumor suppressors and may represent promising therapeutic targets for GBC.

Evaluation of four pyridine analogs to characterize 6-OHDA-induced modulation of mGluR5 function in rat brain using microPET studies.

Micro-positron emission tomography imaging studies were conducted to characterize modulation of metabotropic glutamate subtype-5 receptor (mGluR5) function in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using four analogical PET ligands: 2-[(11)C]methyl-6-(2-phenylethynyl) pyridine ([(11)C]MPEP), 2-(2-(3-[(11)C]methoxyphenyl)ethynyl)pyridine ([(11)C]M-MPEP), 2-(2-(5-[(11)C]methoxypyridin-3-yl)ethynyl)pyridine ([(11)C]M-PEPy), and 3-[(2-[(18)F]methyl-1,3-thiazol-4-yl)ethynyl]pyridine ([(18)F]M-TEP). A total of 45 positron emission tomography (PET) imaging studies were conducted on nine male Sprague-Dawley rats within 4 to 6 weeks after unilateral 6-OHDA lesioning into the right medial forebrain bundle. The severity of the lesion was determined with [(11)C]CFT ([(11)C]2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane), a specific and sensitive ligand for imaging dopamine transporter function. The binding potential (BP) images were processed on pixel-by-pixel basis by using a method of the distribution volume ratio with cerebellum as a reference tissue. The values for BP were determined on striatum, hippocampus, and cortex. [(11)C]CFT binding was decreased on the lesioned (right) striatum by 35.4%+/-13.4% compared with the intact left striatum, indicating corresponding loss of presynaptic dopamine terminals. On the same areas of the lesioned striatum, three of the four tested mGluR5 ligands showed enhanced binding characteristics. The average differences between the right and left striatum were 4.4%+/-6.5% (P<0.05) with [(11)C]MPEP, -0.1%+/-1.7% (P>0.05) with [(11)C]M-MPEP, 3.9%+/-4.6% (P<0.05) with [(11)C]M-PEPy, and 6.6%+/-2.7% (P>0.05) with [(18)F]M-TEP. The enhanced binding was also observed in the right hippocampus and cortex. These studies showed that glutamatergic neurotransmission might have a complementary role in dopaminergic degeneration, which can be evaluated by in vivo PET imaging.

Modulation of dopaminergic and glutamatergic brain function: PET studies on parkinsonian rats.

UNLABELLED: Degeneration of dopaminergic neurons of the substantia nigra pars compacta is a cardinal feature of Parkinson's disease (PD). Although uncertain, the pathology has been suggested to derive from a malfunction of the complex interaction between dopaminergic and metabotropic glutamate receptors (mGluRs). To further address this issue, we investigated the imaging profile and expression of dopamine D(2) receptors and mGluRs in a classic parkinsonian rodent model induced by the toxin 6-hydroxydopamine. METHODS: Adult male Sprague-Dawley rats (250-300 g) received a stereotaxic injection of 8 mug/2 muL of 6-hydroxydopamine (n = 6) or saline solution (n = 4) in the right medial forebrain bundle. Small-animal PET was performed on all rats 4 wk after the surgical procedure to assess dopamine transporter (DAT) status using (11)C-2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane (CFT), as well as dopamine D(2) receptor and mGluR(5) modulation using (11)C-raclopride and 2-(11)C-methyl-6-(2-phenylethynyl)-pyridine ((11)C-MPEP), respectively. Behavioral studies were also conducted 6 wk after lesioning by d-amphetamine challenge. Immunohistochemistry and Western blotting were carried out at 8 wk after lesioning to confirm dopamine fiber, neuronal loss, and level of striatal mGluR(5) expression. RESULTS: PET images showed decreased (11)C-CFT binding on the lesioned side, including the structures of the striatum, hippocampus, and cortex, compared with the contralateral intact side. Interestingly, dopamine D(2) receptors and mGluR(5) upregulation were observed in the right striatum, hippocampus, and cortex, using (11)C-raclopride and (11)C-MPEP, respectively. A negative correlation was also found between the percentage change in mGluR(5) expression and DAT function. Finally, tyrosine hydroxylase immunoreactivity confirmed both dopamine fiber loss (t test, P < 0.01) and neuronal loss (t test, P < 0.01) on the lesioned side. These changes were accompanied by a strongly enhanced mGluR(5) expression in the right striatum of the lesioned side analyzed by Western plot. CONCLUSION: These findings support the existence of compensatory mechanisms in nigrostriatal dopamine degeneration and provide new insights that help further dissect some of the pathways underlying neurodegeneration. In addition, these results reconfirm that PET is a valuable tool for multilevel receptor studies, significantly contributing to the understanding of pathogenic mechanisms and ultimately opening new avenues in the study of neuroprotective approaches toward PD.