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Traumatic Brain Injury (TBI) is common amongst military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer’s disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 NIA-AA research framework1, by measuring tau, β-amyloid and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI.Seventy male Vietnam war veterans — 40 with TBI (aged 68.0±2.5 years) and 30 controls (aged 70.1±5.3 years) — with no prior diagnosis of dementia or mild cognitive impairment underwent β-amyloid (18F-Florbetaben), tau (18F-Flortaucipir) and18F-FDG PET. The TBI cohort included 15 participants with mild, 16 with moderate, and 9 with severe injury. β-amyloid level was calculated using the Centiloid (CL) method and tau was measured by Standardized Uptake Value Ratios (SUVR) using the cerebellar cortex as reference region. Analyses were adjusted for age and APOE-e4. The findings were validated in an independent cohort from the ADNI-DOD study.There were no significant nor trending differences in β-amyloid or tau levels or18F-FDG uptake between the TBI and control groups before and after controlling for covariates. The β-amyloid and tau findings were replicated in the ADNI-DOD validation cohort and persisted when the AIBL-VETS and ADNI-DOD cohorts were combined (114 TBI vs 87 controls in total). These findings suggest that TBI is not associated with the later life accumulation of the neuropathological markers of AD.

Tau deposition plays a critical role over cognition and neurodegeneration in Alzheimer’s disease (AD). Recent generation tracers have high target to background ratios giving a wide dynamic range that may improve sensitivity for detection of low levels of tau (Pascoal, Shin et al. 2018). Building on previous evidence, this study aims to characterize the effects of tau deposition as assessed by 18F-MK6240, in a large cohort of patients across the AD disease spectrum.A total of 464 participants, enrolled in the AIBL-ADNeT study, underwent 18F-MK6240 tau PET, 18F-NAV4964 Aβ PET, 3D structural MRI (hippocampal and whole-brain cortical volumes) and extensive neuropsychological evaluation. Participants included 266 cognitively unimpaired controls (CU), 112 patients with mild cognitive impairment (MCI), and 86 patients with probable AD dementia. Evaluation included the characterization of the pattern and degree of 18F-MK6240 tracer retention in each clinical group as well as assessment of the relationship between 18F-MK6240 and age, Aβ imaging, brain volumetrics and cognition in each of the clinical groups. Standard uptake value ratios (SUVR) were estimated in four predefined composite regions of interest (ROIs), reflecting the stereotypical progression of tau pathology in the brain: 1. Mesial-temporal (Me), 2. Temporoparietal (Te), 3. Remainder of neocortex (R), 4. A temporal meta-region termed metaT+.18F-MK6240 retention was higher in AD patients compared with all other diagnostic groups, with 18F-MK6240 distinguishing patients with AD from CU individuals, with the highest effect size obtained in the amygdala (Cohen’s d: 2.07), and Me (Cohen’s d: 1.99). When considering Aβ status, 18F-MK6240 not only was able to distinguish between Aβ+ AD patients and Aβ- CU (Cohen’s d: 2.23), but also between Aβ+ and Aβ- CU (Cohen’s d: 1.32). In Aβ- CU, 18F-MK6240 retention in Me showed a slow age-related increase, while 18F-MK6240 retention was higher in younger elderly Aβ+ AD patients compared to their older counterparts. There was a sigmoidal relationship between subthreshold tau and Aβ, providing evidence for a very slow but steady increase in subthreshold tau prior to a fast increase in cortical Aβ. Moreover, a non-linear relationship between Aβ and tau suggest that detectable cortical Aβ precedes detectable cortical tau. While age was the main predictor of cognitive decline in CU, and Aβ and hippocampal volume in MCI, the main predictor of cognitive decline in the AD group was tau. High tau was associated with faster cognitive decline and clinical progression in the CU and MCI groups.This large study provides further evidence that 18F-MK6240 discriminates CU from AD and, most importantly, Aβ+ from Aβ- CU individuals with high effect sizes, suggesting that 18F- MK6240 can detect lower tau levels than earlier tau tracers, crucial for early detection of tau deposition as well as tracking small tau changes over time. In conclusion, identification of regional cortical tau deposition has critical diagnostic and prognostic implications and should become a standard tool to identify individuals at risk, as well as outcome measure, in both anti- Aβ and anti-tau trials.

Behavior and cognition in humans and other primates rely on networks of brain areas guided by the frontal cortex. The marmoset offers exciting new opportunities to study links between brain physiology and behavior, but the functions of frontal cortex areas are still being identified in this species. Here, we provide the first evidence of visual receptive fields in the marmoset dorsolateral frontal cortex, an important step toward future studies of visual cognitive behavior.

Recent studies suggest that females and males show different levels of susceptibility to neuropsychological disorders which might be related to sex differences in executive control of behaviour. Music, as a cognitively salient factor, might influence cognitive functions; however, it is unclear how sex and music interact in influencing executive control of behaviour in a dynamic environment. We tested female and male participants in a computerized analogue of the Wisconsin Card Sorting Test (WCST) while listening to music or in silence. We found that music decreased the percentage of correct trials in both sexes. While music decreased response time in females, it had an opposite effect in males. Response time increased in error trials (error slowing), and music sex-dependently influenced error slowing. Conflict between potential rules adversely influenced performance in the current trial (conflict cost) in both sexes and listening to music increased conflict cost. These findings suggest that music shows both adverse and beneficial effects on various behavioural measures in the WCST, some of which are sex-dependent. Our findings suggest that in using music as an adjunct for rehabilitation of neuropsychological disorders, both adverse and beneficial effects and sex dependency need to be considered.

Commission of errors and conflict between choices might induce behavioral modulations through adjustments in the executive control of behavior and altered patterns of these modulations are detected in neuropsychiatric disorders. We examined the effects of transcranial Direct Current Stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) on error- and conflict-induced behavioral modulations. Two separate cohorts of participants performed two clinically relevant tests of executive control, respectively. In the Wisconsin Card Sorting Test (WCST), the relevant rule for matching items frequently changed and therefore participants had to detect these unannounced changes by trial and error and alter their rule-based behavior. In the Stop task, participants had to rapidly respond to a directional go-signal but inhibit their responses when a stop signal appeared after the go-signal. Each participant received tDCS (sham, cathodal or anodal) in three separate sessions. Errors led to a slower response in the next trial (post-error slowing) in both tasks. The tDCS significantly modulated the post-error slowing in both tasks but did not affect the behavioral adjustments induced by the conflict. The modulation of post-error slowing by tDCS were polarity-dependent and also trial specific appearing immediately after errors. In the WCST and Stop task, the post-error slowing may reflect different processes involved in shifting the behavior-guiding rule and adjustments in inhibitory control of responses, respectively, and we found that the effective tDCS polarity differed between the two tasks. Here, we show that in two separate cognitive tasks direct current stimulation of DLPFC significantly modulated error-induced behavioral modulations.

The prefrontal cortex is known as a region, most directly involved in cognitive control. One of the most intriguing mysteries in neuroscience is how cognitive control is being implemented. In this thesis, I focused on three prefrontal regions, namely the frontal visual areas (involved in the final stage of cortical processing of saccadic eye movements and visual spatial attention), the frontal pole cortex (involved in multitasking, prospective memory, and exploratory behaviour) and the dorsolateral prefrontal cortex (involved in top-down cognitive control on behavioural modulation during conflict-inducing tasks) and investigated their contributions to cognitive control processes in humans and non-human primates.

Objective: To investigate one possible mechanism for the observed relaxant effect of A. millefolium (Achillea millefolium), in the present study the inhibitory effect of the extract of this plant on muscarinic receptors was examined. Materials and Methods: The effects of three concentrations of aqueous-ethanolic extract, 10 nM atropine, and saline on muscarinic receptors were tested in three conditions: In non incubated tracheal smooth muscle (group 1), tracheal chain incubated with propranolol and chlorpheniramine (group 2), and the one incubated with propranolol (group 3). Results: The EC50 obtained in the presence of all three concentrations of the extract were significantly higher compared to saline in groups 2 and 3 (P < 0.001and P < 0.01 in group 2 and 3 respectively). The EC50 obtained in the presence of all concentrations of the extract in group 2 were significantly improved compared to groups 1 and 3 (P < 0.05 to P < 0.001). The maximum responses to methacholine in presence of only the higher concentration of the extract (0.8mg/ml) was significantly lower than that of saline in groups 1 (P < 0.05). There was neither significant difference between slopes of methacholine-response curves obtained in the presence of different concentrations of the extract and that of saline nor between the three groups. The values of (CR-1), obtained in the presence of all concentrations of the extract, were significantly lower compared to atropine in the first group but were not significantly different in other groups. The values of (CR-1) obtained in the presence of all concentrations of the extract were significantly improved in groups 2, compared to groups 1 and 3 (P < 0.05 to P < 0.001). Conclusion: These results showed an inhibitory effect for the extract of A. millefolium on muscarinic receptors of tracheal smooth muscle. A histamine (H1) receptor blockade was also suggested for the extract.

Background: 5-Bromo-2-deoxyuridine (BrdU) has been a principal marker for mitotic cells in studies of adult neurogenesis. The method consists of a pulse injection of BrdU into the intraperitoneal cavity followed by a variable survival time allowing for tracking the divided cells and their progeny. However, such exogenous markers may produce toxic effects. Aim of this study was determined the effects of Brdu on spatial memory in the adult rat. Materials and Methods: 16 Wistar rats were used in this experimental study. The rats were randomly divided into 2 groups (N=8 in each group), as follows: control and Brdu (50 mg/kg). Brdu was administered intraperitoneally for 6 weeks and then animals were used for behavioral testing in the Morris water maze. The data were analyzed with repeated measure’s ANOVA.Results: Our present findings show that there were no differences in the path length, escape latency and swim speed between control and Brdu-administrated groups.Conclusion: This study show that Brdu (exogenic proliferation marker) did not has side effects on spatial memory in the adult rats.

Chronic obstructive pulmonary disease (COPD) is a epidemic disease which is mainly due to cigarette smoking. The effect of carvacrol on systemic inflammation in guinea pig model of COPD was examined in the present study.Guinea pigs of both sexes were divided into 6 groups, including: control, COPD, COPD+drinking water containing three concentrations of carvacrol and COPD+dexamethasone. Animals were exposed to cigarette smoke for 3 months in order to induce animal model of COPD. Weight changes, serum levels of IL-8 and malondialdehyde (MDA) as well as total and differential white blood cell (WBC) were measured (n=5 for control and COPD groups and n=6 for other groups).Serum levels of IL-8 and MDA, total WBC (p0.01 for all cases) and eosinophil counts (p0.05) were increased and weight changes were decreased (p0.05) in COPD group compared to controls. Serum MDA level and total WBC in treated groups with two higher carvacrol concentrations, eosinophil, neutrophil and lymphocyte percentage in those treated with its high concentration as well as IL-8 level and weight change in treated groups with its all concentrations and in dexamethasone treated group were significantly improved compared to COPD group (p0.05 to p0.001).These results showed a preventive effect of the carvacrol on all measured parameter in COPD guinea pigs which was comparable to the effect of dexamethasone at used concentrations.

The effect of safranal (one of the constituents of Crocus sativus) on ovalbumin (OVA) sensitized guinea pigs was examined.One group of sensitized guinea pigs were given drinking water alone (group S), three groups drinking water containing three concentrations of safranal and one group contain dexamethasone (S + D). Tracheal responses (TR) of the animals to methacholine as effective concentration causing 50% of maximum response (EC(50) M), TR to 0.1% OVA, relative to contraction induced by 100 μM methacholine, IL-4, IFN-γ, total NO and nitrite levels in serum were measured.The TR to both methacholine and OVA, the level of total NO, nitrite and IL-4 significantly increased but IFN-γ and IFN-γ/IL-4 ratio was decreased in group S compared controls (p0.05 to p0.001). The TR to both methacholine and OVA in treated animals with dexamethasone and all concentrations of safranal were significantly decreased compared to S group (p0.01 to p0.001). The level of serum IL-4 in treated guinea pigs was significantly decreased but IFN-γ and IFN-γ/IL-4 ratio was increased compared to S group (p0.01 to p0.001). The levels of total NO and nitrite were significantly decreased in treated groups compared to sensitized group (p0.05 to p0.001).These results showed a preventive effect for safranal on tracheal responses and serum cytokine, total NO and nitrite levels as well as increased Th1/Th2 balance in sensitized guinea pigs.

Different pharmacological effects of Achillea millefolium including its relaxant effect on smooth muscle have been shown previously. In the present study the stimulatory effect of the plant extract on β-adrenoceptor of tracheal muscle was examined in order to investigate one possible mechanism for its observed relaxant effect. Effect of three concentrations of hydroethanol extract, 10 nM propranolol, and saline on β-adrenoceptor was tested in two experimental groups including; nonincubated tracheal smooth muscles (group 1) and incubated tracheal smooth muscle with chlorpheniramine (group 2). Concentration response curves to isoprenaline were performed in precontracted tracheal smooth muscle in the presence of the extract, propranolol and saline. Values of EC 50 and CR-1 were measured. Leftward shifts in isoprenaline curves were observed in the presence of medium and high concentrations of the extract compared with saline in both groups. The values of EC 50 obtained in the presence of medium and high concentrations of the extract only in group 1 were nonsignificantly lower than that of saline. The values of CR-1 obtained in the presence of all concentrations of the extract in both groups were negative and significantly different with that of propranolol. The results indicated a small stimulatory effect of the extract on I¯2-adrenoceptors.

Background Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic disease and a major cause of death and disability. The present study aimed to elucidate pharmacological effects of adipose derived stromal cells (ASCs) on pathological and biochemical factors in a guinea pig model of COPD. Guinea pigs were randomized into 5 groups including: Control, COPD, COPD + intratracheal delivery of PBS as a vehicle (COPD-PBS), COPD + intratracheal delivery of ASCs (COPD-ITASC) and COPD + intravenous injection of ASCs (COPD-IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was performed immediately after the end of animal exposure to cigarette smoke and 14 days after that, white blood cells, oxidative stress indices and pathological changes of the lung were measured. Results Compared with control group, emphysema was clearly observed in the COPD and COPD-PBS groups (p Conclusion Cell therapy with ASCs can help in reducing oxidative damage during smoking which may collectively hold promise in attenuation of the severity of COPD although the lung structural changes couldn’t be ameliorated with these pharmacological therapeutic methods.