Traumatized humans with high UCR showed similarly high responses to the CS+ and CS-. While all groups showed a positive association between the UCR and CS+ response, the UCR correlated positively with the CS- response in traumatized humans only. Our findings suggest that an elevated response to aversive stimuli predicts deficits in conditioned safety memory in those at risk for trauma-related disorders and confirms that impaired safety learning could be a valid biomarker for these diseases.Alzheimer's disease (AD) is the foremost cause of dementia among other neurodegenerative diseases, leading to memory loss and cognitive deficits. AD has gained extensive attention in research for exploring possible interventions. One promising field is natural substances and compounds that could provide a wide range of neuroprotection against AD. This study aimed to investigate the possible effects of melatonin (MEL) and resveratrol (RES) in improving memory deficits in a sporadic mouse model of AD. Memory deficit was induced using AlCl3 and d-galactose for generating an AD mouse model. Mice were randomly distributed into five groups (n = 13) control, AD, AD + MEL (AD mice treated with 80 mg/kg of MEL), AD + RES (AD mice treated with 40 mg/kg of RES), and AD + Combination)AD mice that received 80 mg/kg MEL and 40 mg/kg RES). A novel object recognition task (NORT) and passive avoidance task (PAT) were used for assessing memory. Moreover, acetylcholinesterase (AChE) level, brain-derived neurotrophic factor (BDNF), and cAMP-response element binding (CREB) protein expression were measured in the prefrontal cortex tissue. Our results showed that MEL significantly improved memory deficits in both the NORT and PAT of the AD model, while RES improved the PAT only in the AD model. Co-treatment with MEL and RES exerted beneficial additive effects on recognition memory impairment in the AD mouse model. Moreover, our results demonstrated that both MEL and RES enhanced the cholinergic system and BDNF and CREB signaling pathways in the prefrontal cortex in an AD mouse model.Mild cognitive impairment (MCI) is considered to be the early stage of Alzheimer's disease (AD), but the diagnostic predictive markers for MCI patients are still unclear. Here we have identified the brain function activity changes in MCI patients by using the resting-state functional magnetic resonance imaging (rs-fMRI). A total of 28 MCI patients and 38 age- and gender-matched healthy controls from the Wuxi Mental Health Center were recruited, and their abnormal spontaneous brain activities in the MCI were examined. The results showed that, compared with the healthy controls, MCI patients exhibited reduced regional homogeneity (ReHo) in the right superior temporal gyrus, right middle temporal gyrus, left angular gyrus and superior marginal gyrus. In addition, the correlation analysis revealed that ReHo in these regions were not correlated with the AD Assessment Scale-Cognitive score in MCI. We concluded abnormalities in the right superior temporal gyrus, right middle temporal gyrus, left angular gyrus and superior marginal gyrus with MCI, suggesting that the right language network may be impaired in MCI, which may provide a better understanding of dementia progression and potentially comprehensive treatment in MCI. Antipsychotics are a cornerstone of pharmacological treatment of schizophrenia. Improved understanding of the dose-response relationship of antipsychotics in terms of efficacy, adverse effects, and mortality can help to optimize the pharmacological treatment of schizophrenia. This narrative literature review summarizes current evidence on the relationship of antipsychotic dose with efficacy, adverse effects, and mortality in patients with schizophrenia. The efficacy of antipsychotics generally appeared to be highly dose-dependent in the acute phase of schizophrenia, with each antipsychotic having a specific dose-response curve. The presence or absence of dose-dependency and its extent varied according to the type of adverse effect. Parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment appeared to be dose-related. The following adverse effects might be at least somewhat dose-dependent akathisia, tardive dyskinesia, osteoporosis, sexual dysfunction, diabetes mellitus, myocardial infr investigations with larger sample sizes and more robust study designs that focus on each antipsychotic agent are needed.Deep brain stimulation (DBS) has shown positive clinical results in neurodegenerative diseases. Previous work from our group showed that a single session of DBS to the anteromedial thalamic nucleus (AMN) in awake rats, increased proliferation of stem/progenitor cells in the dentate gyrus (DG) of the hippocampus. We thought to examine the effect of single versus multiple sessions of DBS to the AMN in modulating adult hippocampal neurogenesis. Rats received unilateral single session, multiple sessions or no electrical stimulation (sham) in the right AMN. Rats received 5'-bromo-2'-deoxyuridine (BrdU) injections and were followed over a period of 1 week or 4 weeks. https://www.selleckchem.com/products/Gefitinib.html Single session of electrical stimulation induced a 1.9-fold increase in the number of proliferating BrdU positive cells after one week from stimulation and a 1.8-fold increase at four weeks post stimulation, both in the ipsilateral DG. As for multiple sessions of stimulation, they induced a 3- fold increase that extended to the contralateral DG after 4 weeks from stimulation. Spatial reference memory was tested in the Y-maze test by examining novel arm exploration. Both single and multiple sessions of stimulation prompted an increase in novel arm exploration at week 4, while only the multiple sessions of stimulation had this effect starting from week 1. This study demonstrates that sustained activation of the AMN boosts neurogenesis and improves spatial reference memory.Oxidative stress and the nitric oxide (NO) pathway are involved in the development of opioid analgesic tolerance and dependence. Simvastatin modulates NO and oxidative stress, so the present study aimed to investigate its effect on the development and expression of morphine analgesic tolerance and withdrawal signs in mice. Morphine tolerance and dependence were induced by twice daily morphine injection (10 mg/kg, s.c.) for 5 consecutive days. Tolerance was assessed by the hot-plate test and dependence by naloxone challenge, on the sixth day. To determine if the NO is involved in the effects of simvastatin, mice were pre-treated with l-arginine (200 mg/kg) or the NO synthesis inhibitors (L-NAME; 30 mg/kg) along with simvastatin (300 mg/kg). The results showed that acute and chronic administration of simvastatin reversed the antinociceptive tolerance of morphine and attenuated withdrawal signs in morphine-dependent mice, and this effect is reversed by l-arginine and augmented by l-NAME. Also, the concentration of NO and oxidative stress factors such as malondialdehyde content, total thiol, and glutathione peroxidase (GPx) activity in brain tissues was evaluated.