Melatonin Protects Against Titanium Oxide-Induced Neurotoxicity: Neurochemical, Neurobehavioral, and Histopathological Evidences.

titania (titanium dioxide, TiO2) is known to induce neurotoxicity and CNS dysfunctions. Numerous studies have explored the neuroprotective effects of melatonin against neurotoxicity. This study evaluates the potential of melatonin to protect against titania-induced neurotoxicity and the role of the Keap1/Nrf2/ARE signaling pathway. One group of animals were treated with Titania (0.045 and 0.075 g/rat) alone while the other with added melatonin (1 mg/kg and 3 mg/kg) and behavioral alterations were assessed using OFT (open field test). Neurochemical and histopathological changes were also studied in the hippocampus by analyzing kelch ECH associating protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and antioxidant response element (ARE). It was seen that the animals with added Melatonin had improved behavioral scores in the OFT, like anxiety and motor dysfunction triggered by TiO2. Melatonin also reduced lipid peroxidation, ROS, GSSG, IL1ß, TNFα, Bax, and Keap1 levels, but boosted GSH, GPx, GR, SOD,IL10,IL4, Bcl2, Nrf2, and ARE levels and improved quadruple mitochondrial enzyme complex activity in titania-treated animals. Histopathological examination showed melatonin induced cytoprotection against vacuolization and necrosis in granular cells of DG and pyramidal cells of CA1 area of the hippocampus. In our study, pretreatment with melatonin reduced titania-induced neurotoxicity in the hippocampus through a mechanism potentially mediated by the Keap-1/Nrf2/ARE pathway.

Hypothesized neuroprotective effect of minocycline against COVID-19-induced stroke and neurological dysfunction: possible role of matrix metalloprotease signaling pathway.

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.

Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways.

OBJECTIVES: Present study investigated the neuroprotective effects of selegiline and the molecular mechanisms involved in methamphetamine-induced neurotoxicity. MATERIALS AND METHODS: Male wistar rats were randomly divided into six groups (10 rats in each group). Group 1 and group 2 received normal saline and methamphetamine (10 mg/kg), respectively. Groups 3, 4, 5 and 6 were treated simultaneously with methamphetamine and selegiline. From day 22 to day 28, forced swim test, elevated plus maze, and open field test were conducted to assess mood (anxiety and depression) levels, and from day 17 to day 21, Morris Water Maze was conducted for cognition assessment. On day 29, hippocampus of the animals were isolated and evaluated by ELISA method for oxidative, antioxidant, and inflammatory factors and expression levels of active (total) and inactive (phosphorylated) forms of cyclic AMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt (Protein Kinase B) and glycogen synthase kinase 3 (GSK3) proteins. RESULTS: Selegiline reduced behavioral impacts caused by methamphetamine in all doses. Methamphetamine administration may improve malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta and GSK3 (both forms). Moreover, methamphetamine reduced the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase, amount of BDNF, CREB and Akt (both forms). CONCLUSION: Current research showed that selegiline can protect the brain from methamphetamine-prompted neurodegeneration, and this could be intervened by CREB -BDNF or Akt-GSK3 signaling pathways.