Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. Hallmarks of AD are memory impairments and cognitive deficits, but non-cognitive impairments, especially motor dysfunctions are also associated with the disease and may even precede classic clinical symptoms. With an aging society and increasing hospitalization of the elderly, motor deficits are of major interest to improve independent activities in daily living. Consistent with clinical findings, a variety of AD mouse models develop motor deficits as well. We investigated the motor function of 3- and 7-month-old Tg4-42 mice in comparison to wild-type controls and 5XFAD mice and discuss the results in context with several other AD mouse model. Our study shows impaired balance and motor coordination in aged Tg4-42 mice in the balance beam and rotarod test, while general locomotor activity and muscle strength is not impaired at 7 months. The cerebellum is a major player in the regulation and coordination of balance and locomotion through practice. Particularly, the rotarod test is able to detect cerebellar deficits. Furthermore, supposed cerebellar impairment was verified by 18 F-FDG PET/MRI. Aged Tg4-42 mice showed reduced cerebellar glucose metabolism in the 18 F-FDG PET. Suggesting that, deficits in coordination and balance are most likely due to cerebellar impairment. In conclusion, Tg4-42 mice develop motor deficits before memory deficits, without confounding memory test. Thus, making the Tg4-42 mouse model a good model to study the effects on cognitive decline of therapies targeting motor impairments.
The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice.
Remaining filling material and dentine removal were similar for all canal filling techniques. Regaining working length was significantly faster for GuttaCore compared with Thermafil and vertically compacted gutta-percha. Procedural errors occurred during retreatment of severely curved root canals with the ProTaper Universal Retreatment files in 5 of 60 canals (8%).
We report the controlled synthesis of polyethylene (PE) via catalyzed chain growth (CCG) carrying a cationic end-group. CCG and subsequent iodine treatment give rise to both low dispersed PE and a high degree of end-group functionalization. The end-group can be further substituted by 3-dimethylamino-1-propanol leading to a well-defined cationic functionality, as validated by NMR spectroscopy. The positive charge enables matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS) of these PE chains with an excellent signal-tonoise ratio. Moreover, the charged PE acts as a phase transfer catalyst (PTC) in a nucleophilic substitution with excellent yields even in comparison to well-established conventional PTCs. This new PE-based catalyst is completely recoverable by simple filtration due to its temperature-dependent solubility. On the basis of this powerful phase-transfer ability, we prepared charged PE loaded by an anionic dye via the extraction of the dye from aqueous to organic phase. Atom transfer radical polymerization (ATRP) initiator and acrylate-based end-groups were also introduced to the polymer system resulting in a positively charged PE-based macroinitiator/macromonomer, expanding the array of applications of this new type of polymer. Further block copolymerization of the ATRP functionalized PE with n-butyl acrylate was conducted successfully.
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