Networks of synaptically connected neurons underlie all brain functions. Various cell-cell signaling and extrinsic molecules influence synapse assembly at the synaptic site. Calcium ions play a significant role in signal transduction pathways that control various neuronal functions. Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMK II) is an important mediator of calcium signaling in neurons, it plays an essential role in controlling synaptic strength and plasticity, and it is highly expressed in the cytosol of developing neurons, especially in presynaptic neurons. However, the precise role of CaMKII in synapse formation and synaptic transmission has not yet been determined. We hypothesized that CaMKII activity could be necessary for synapse formation and synaptic transmission. To test whether CaMKII activity is required for the synapse formation and synaptic transmission, the identified neurons visceral dorsal 4 (VD4 – presynaptic) and its postsynaptic partner left pedal dorsal 1 (LPeD1) from the freshwater snail Lymnaea stagnalis were paired in soma-soma configuration in cell culture. The soma-soma paired cells recapitulated their excitatory connections in vitro. To test the possible role of CaMKII in synapse formation and synaptic transmission, the in vitro paired neurons were exposed to a CaMKII-specific inhibitor KN-93 and its inactive analog KN-92. The incidence of synapse formation and efficacy of synaptic transmission was tested electrophysiologically.

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Anticoagulants ; Observational Study ; Venous Thrombosis ; Warfarin

Objective: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. Methods: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. Results: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. Conclusion Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.