Oksana Fihurka

Melatonin, insulin, and Δ9-tetrahydrocannabinol (THC) have been shown to reverse cognitive deficits and attenuate neuropathologies in transgenic mouse models of Alzheimer’s disease (AD) when used individually. Here, we evaluated the therapeutic properties of long-term intranasal treatment with a novel nanoformulation containing melatonin, insulin, and THC in aged APPswe/PS1ΔE9 (APP/PS1) mice, a transgenic model of AD. Transgenic mice at the age of 12 months were intranasally administered with a new nanoformulation containing melatonin, insulin, and THC at doses of 0.04, 0.008, and 0.02 mg/kg, respectively, once daily for 3 months. The spatial memory of the mice was assessed using the radial arm water maze (RAWM) test before and after drug treatment. Brain tissues were collected at the end of the treatment period for the assessment of Aβ load, tauopathy state, and markers of mitochondrial function. The RAWM test revealed that the treatment with the melatonin–insulin–THC (MIT) nasal spray improved the spatial learning memory of APP/PS1 mice significantly. Results of protein analyses of brain homogenates indicated that MIT treatment significantly decreased the tau phosphorylation implicated in tau toxicity (p < 0.05) and the expression of CKMT1 associated with mitochondrial dysfunction. Moreover, MIT significantly decreased the expression of two mitochondrial fusion-related proteins, Mfn2 and Opa1 (p < 0.01 for both), while increasing the expression of a mitophagy regulator, Parkin, suggesting a compensatory enhancement of mitophagy due to MIT-promoted mitochondrial fusion. In conclusion, this study was the first to demonstrate the ability of an MIT nanoformulation to improve spatial memory in AD mice through its multi-targeting effects on Aβ production, tau phosphorylation, and mitochondrial dynamics. Thus, MIT may be a safe and effective therapeutic for AD.

Background. Plant-microbial fuel cell (PMFC) is an innovative biotechnology for the environmentally safe bioelectricity generation. The widespread use of bioelectrical systems (biosystems) is hindered by their insufficient efficiency due to limiting knowings of the relationship between bioelectricity generation and features of their biotechnological components. Objective. Тhe purpose of this study was to analyze the role of the plants morphological parameters and structure features of biomodules on generation of bioelectricity. Methods. Biometric, biogravimetric, voltammetric, and statistical analysis methods were used to assess the relationship between plant`s accumulated mass of leaf and roots, multielectrode design of biosystem and bioelectricity generation. Results. PMFC based on sedge C. hirta with the largest accumulated total dry leaf/stem and root mass and also the rhizome-like and developed fibrous root system were characterized by the highest power output compared to other biosystems. The power density was 970 ± 22 mW m-2 PGA. The parallel stacking of biomodules leads to obtain current output about 108.7 mA. That is why the developed biotechnological systems can be recommended as a foundation for the development of power supply for WiFi microcontrollers that consume 100 mA or for charging batteries. Conclusions. Sedge С. hirta were appeared as the more suitable plants for biological component of biosystem of bioelectricity generation. Power density of С. hirta based PMFC exceeded the one of based on other plants in 9.3–37.9%.The type and level of development of the root system and of the above-ground photosynthetic surface of plant are an important prognostic factors of the PMFC perfomance. A 10-fold increase of the electrode surface of one biomodule results in 3.95 times increase of power density at 200 W. The multielectrodeity biomodule reveals as another lever for increasing the efficiency of biosystems which allows obtaining significantly increase power density and current density in the range of electrical resistance from 50 to 500 W.

THC has been used as a promising treatment approach for neurological disorders, but the highly psychoactive effects have largely warned off many scientists from pursuing it further. We conducted an intranasal treatment using low-dose THC on 12-month-old APP/PS1 mice daily for 3 months to overcome any potential psychoactive response induced by the systemic delivery. Our results demonstrate that the THC nasal treatment at 0.002 and 0.02 mg/kg significantly slowed the memory decline compared to that in the vehicle-treated transgenic mouse control group. An enzyme-linked immunosorbent assay showed that the Aβ1–40 and 1–42 peptides decreased in the THC-treated groups. The Western blot data indicate that long-term low-dose THC intranasal administration promoted p-tau level reduction and mitochondrial function marker redistribution. The blood biochemical parameter data demonstrate some insignificant changes in cytokine, immunoglobulin, and immune cell profiles during intranasal THC treatment. Intranasal delivery is a non-invasive and convenient method that rapidly targets therapeutics to the brain, minimizing systemic exposure to avoid unwanted adverse effects. Our study provides new insights into the role of low-dose THC intranasal treatment as a pharmacological strategy to counteract alterations in Alzheimer’s disease-related cognitive performance.