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Brain Targeted Drug Delivery Systems
Published in Ambikanandan Misra, Aliasgar Shahiwala, In-Vitro and In-Vivo Tools in Drug Delivery Research for Optimum Clinical Outcomes, 2018
Manisha Lalan, Rohan Lalani, Vivek Patel, Ambikanandan Misra
Neurotoxicity events are the adverse effects on the chemistry, anatomy, and physiology of the nervous system (during development or at maturity) caused by chemical, biological, or physical means. Some of the drugs, metals, industrial chemicals, etc. are known neurotoxic agents. They may cause neuropathies or affect neurotransmission. The neurotoxicity assessment required by the Environmental Protection Agency and Organisation for Economic Co-operation and Development guidelines focus on behavioral and histopathology evaluations of the nervous system, which are expensive, time consuming, do not correlate well with human neurotoxicity, and are not apt for high throughput screening. In-vitro models have been generated to seek information on cell biology and neuronal functioning. A range of in-vitro systems are available with ascending biological complexity to complement the in-vivo assessment as shown in Figure 8.2. Some of the key parameters guiding the success of such evaluations are maintaining the heterogeneity of nervous system in-vitro, lack of cellular hemostatic mechanisms, interspecies differences, exposure time, age of the neuronal units in model, etc. However, the major drawback of in-vitro systems is the inability to provide behavioral end points (Barbosa et al. 2015; Radio and Mundy 2008).
Effects of increased salinity on oxidative stress status in the freshwater mussel Unio ravoisieri
Published in Chemistry and Ecology, 2023
Amal Lassoued, Noureddine Khalloufi, Wiem Saidani, Abdelhafidh Khazri, Neziha Ghanem-Boughanmi, Jaouad Bouayed, Mossadok Ben-Attia
It has been shown that AChE activity was inhibited by high amounts of H2O2, suggesting a strong relationship between the activities of AChE and CAT in aquatic organisms [49]. In the present work, we further tested the hypothesis if high salinity levels may mediate neurotoxicity in freshwater mussels, by assessing AChE activity. In fact, AChE activity has significantly increased following the exposure to the highest concentrations of salinity (i.e. 5 and 7.5) in both gills and digestive gland, while the modulating effect of the exposure to the lowest concentration (2.5) was observed only in digestive gland (Figure 5). Although species difference, our results were in support of those of Cailleaud et al. [50] reporting that salinity change resulted in a significant increase in AChE activity of the copepod (Eurytem0ora affinis). In the present study, AChE activity in gills and digestive gland was significantly increased by the highest salinity change, which is indicative of a strong perturbation of AChE activity compared to the control. Thus, osmotic stress caused by increased salinity should affect the rate of acetylcholine, the neurotransmitter that mediates fast excitatory and inhibitory neurotransmission in the molluscan CNS [51].
Experimental and computational analysis of N-methylcytisine alkaloid in solution and prediction of biological activity by docking calculations
Published in Molecular Physics, 2022
Fanny C. Alvarez Escalada, Elida Romano, Silvia Antonia Brandán, Ana E. Ledesma
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have various signalling characters in the central nervous system; human α4β2 is a nicotinic receptor of nicotinic subtype mostly abundant in the brain [41]. Nicotine is a plant alkaloid responsible for the addictive properties of tobacco; it binds with high affinity to the nicotinic acetylcholine receptors α4β2nAChRs and acts as a full agonist. Research works find new use of nAChR partial agonists for the treatment option by smoking cessation, such as cytosine, which diminishes nicotine support and reduces the pleasure from smoking [42]. To evaluate the basis for affinity binding and eventually identify the structural elements, supporting the receptor selectivity of the NMC to nAChRs receptor, we have structurally characterised complexes of that molecule with acetylcholine-binding protein (Ac-AChBP, PDB:4BQT) and human α4β2 nAChR (PDB: 5KXI) receptors. Full details, showing the ligand position in the binding site with NMC docked into each complex, are provided in Figure 6.
Consequences of space radiation on the brain and cardiovascular system
Published in Journal of Environmental Science and Health, Part C, 2021
Catherine M. Davis, Antiño R. Allen, Dawn E. Bowles
Environmental stressors often engender chronic disruptions in the excitatory/inhibitory (E/I) balance in the brain, leading to neurobehavioral dysfunction. The results described above support possible disruptions to E/I balance within the mPFC as an underlying mechanism of radiation-induced neurobehavioral deficits, but this hypothesis has yet to be directly tested. Within the mPFC, parvalbumin (PV) interneurons provide inhibitory input to principal neurons and are critical to maintaining this balance.93 In rodents, x-ray radiation exposure reduces activation of the mPFC (infralimbic cortex), most likely through reductions in GABAergic neurotransmission in PV neurons, leading to deficits in fear-based conditioning.94 Further, total cortical GABA release is also decreased following combined irradiation with gamma rays and 12C.95