Background:The most important cause of neurodegeneration in AD is associated with inflammation and oxidative stress. Probiotics are microorganisms that are believed to be beneficial to human and animals. Probiotics reduce oxidative stress and inflammation in some cases. Therefore, this study determined the effects of probiotics mixture on the biomarkers of oxidative stress and inflammation in an AD model of rats. Methods: In this study, 50 rats were allocated to five groups, namely control, sham, and AD groups with Aβ1-40 intra-hippocampal injection, as well as AD + rivastigmine and AD + probiotics groups with Aβ1-40 intra-hippocampal injection and 2 ml (10 10 CFU) of probiotics (Lactobacillus reuteri, Lactobacillus rhamnosus, and Bifidobacterium infantis) orally once a day for 10 weeks. MWM was used to assess memory and learning. To detect Aβ plaque, Congo red staining was used. Oxidative stress was monitored by measuring the MDA level and SOD activity, and to assess inflammation markers (IL-1β and TNF-α) in the hippocampus, ELISA method was employed. Results: Spatial memory improved significantly in treatment group as measured by MWM. Probiotics administration reduced Aβ plaques in AD rats. MDA decreased and SOD increased in the treatment group. Besides, probiotics reduced IL-1β and TNF-α as inflammation markers in the AD model of rats. Conclusion: Our data revealed that probiotics are helpful in attenuating inflammation and oxidative stress in AD.

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Morphine is the essential opioid drug that use in the clinic to attenuate chronic and severe pain. However long-term administration of morphine leads to the development of anti-nociceptive morphine tolerance. Mechanisms that involved in morphine tolerance are complicated and affect a different part of CNS and change neural circuits. One of the most critical candidates for the development of morphine tolerance are neurotransmitters Which makes the communication between neurons and establish neural circuits. The most prominent neurotransmitters that involved in the development of morphine tolerance are NMDA one of the most popular excitatory neurotransmitter, GABA most important inhibitory neurotransmitter in CNS, and monoaminergic neurotransmitters: dopamine, noradrenaline, adrenaline and serotonin have a lot of crucial roles in CNS. Also, Changes that occur in the level of opioid receptors, neurotransmitters and its receptors make alternation cross-talk between neurons. Understanding these changes help us to have an overall concept about the development of morphine tolerance.

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