ABSTRACT
The increased prevalence of neurodegenerative diseases, especially during the COVID-19 outbreak, necessitates the search for natural immune- and cognitive-enhancing agents. 10-Hydroxy-trans-2-decenoic acid (10-H2DA), the main fatty acid of royal jelly, has several pharmacological activities. Given the fundamental role of astrocytes in regulating immune responses of the central nervous system, we used cortical astrocytes to examine the effect of 10-H2DA on the expression of genes associated with neuroinflammation and the production of neurotrophins, as well as cellular resistance to H2O2-induced cytotoxicity. Astrocytes, pretreated with a range of concentrations of 10-H2DA for 24 h, were exposed to lipopolysaccharide (LPS) for 3 h, after which the expression of proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)) and neurotrophic factors (BDNF, GDNF, and IGF-1) was evaluated. In the absence of LPS, 10-H2DA had no significant effect on the mRNA expression of neurotrophins or cytokines except for IL-1β, which significantly increased with low doses of 10-H2DA (3 µM). 10-H2DA (10 µM) pretreatment of LPS-stimulated cells did not significantly inhibit the expression of cytokine encoding genes;however, it significantly lowered the mRNA expression of GDNF and tended to decrease BDNF and IGF-1 expression compared with LPS alone. Additionally, 10-H2DA did not protect astrocytes against H2O2-induced oxidative stress. Our data indicate no anti-inflammatory, antioxidant, or neurotrophic effect of 10-H2DA in astrocytes undergoing inflammation or oxidative stress. The effect of IGF-1 inhibition by 10-H2DA on neuronal ketogenesis needs investigation.
ABSTRACT
Task 1.1D1.1 Determine the effects of neurotrophic factors on skeletal muscle development and acetylcholine receptor AChR cluster preformation on the bioprinted muscle construct 35 completion during this reporting period, 80 total completion a. Establishing the optimal conditions of agrin treatment to efficiently induceAChR cluster pre-formation on human muscle progenitor cells hMPCs in the bioprinted muscle construct b. Optimizing the bioink composition for 3D bioprinting of muscle constructs with hMPCsc. Determining the viability and differentiation efficiency of hMPCs with agrin treatments in bioprinted constructs d. Establishing the effect of neurotrophic factors ciliary neurotrophic factorCNTF and glial cell line-derived neurotrophic factor GDNF on the hMPC viability and proliferation in the bioprinted muscle construct e. Optimizing the protocol to fabricate PLGA poly-lactic-co-glycolic-acid microspheres as a vehicle for controlled release of neurotrophic factors in the bioprinted muscle constructs f. Evaluating the kinetics of neurotrophic factor release from PLGA microspheres in the bioprinted muscle construct.
ABSTRACT
Antiparkinsonian activity of amantadine was first described in 1969 and was confirmed by several trials in later years. The improvement of parkinsonian symptoms is mild. However, in patients with motor fluctuations a clear reduction of dyskinesia and akinetic crisis could be observed. A possible neuroprotective impact is still under discussion, but lacking evidence. Moreover, amantadine is efficient in the treatment of disorders of vigilance, chronic fatigue (e. g. multiple sclerosis), tardive dykinesia and neurolepticas induced extrapyramidal motor symptoms. The clinical efficacy is caused by manifold mechanism of action. Initially, enhancement of dopaminergic transmission has been observed after amantadine and considered main mechanism of action. Currently, several direct targets are likely such as: (1) aromatic aminoacid decarboxylase, (2) Sigma-1 receptors, (3) nicotinergic receptors, (4) phosphodiesterase, (5) GDNF (glial-cell-derived neurotrophic factor). Dose dependently, there are also other probable targets like NMDA antagonism, serotoninergic-5-HT3 antagonism and potassium channel blockade. Preclinical data suggest an association of both neuroprotective potential and antidyskinetic properties with the antiglutamatergic activity of amantadine. Since the COVID- 19 pandemic, the antiviral efficacy of amantadine generated increasing interest. Several in vitro studies detected inhibition of SARS-CoV-2 virus. These results could support clinical renaissance of this drug in the coming years. © 2021 Wissenschaftliche Verlagsgesellschaft mbH. All rights reserved.