Capacity for consciousness under ketamine anaesthesia is selectively associated with activity in posteromedial cortex in rats.

It remains unclear how specific cortical regions contribute to the brain's overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brain's overall capacity for consciousness. We recorded electroencephalographic responses to cortical electrical stimulation in six rats and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power from spontaneous electroencephalographic activity at each electrode. We repeated these measurements during wakefulness, and during two levels of ketamine anaesthesia: with the minimal dose needed to induce behavioural unresponsiveness and twice this dose. We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly with deeper anaesthesia. The high-dose effect was selectively associated with reduced high frequency/low frequency ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia was associated with similar spectral changes in frontal, but not posterior cortical regions. Thus, activity in the posteromedial cortex correlates with the capacity for consciousness, as assessed by PCIST, during different depths of ketamine anaesthesia, in rats, independently of behaviour. These results are discussed in relation to different theories of consciousness.

General Anesthesia Disrupts Complex Cortical Dynamics in Response to Intracranial Electrical Stimulation in Rats.

The capacity of human brain to sustain complex cortical dynamics appears to be strongly associated with conscious experience and consistently drops when consciousness fades. For example, several recent studies in humans found a remarkable reduction of the spatiotemporal complexity of cortical responses to local stimulation during dreamless sleep, general anesthesia, and coma. However, this perturbational complexity has never been directly estimated in non-human animals in vivo previously, and the mechanisms that prevent neocortical neurons to engage in complex interactions are still unclear. Here, we quantify the complexity of electroencephalographic (EEG) responses to intracranial electrical stimulation in rats, comparing wakefulness to propofol, sevoflurane, and ketamine anesthesia. The evoked activity changed from highly complex in wakefulness to far simpler with propofol and sevoflurane. The reduced complexity was associated with a suppression of high frequencies that preceded a reduced phase-locking, and disruption of functional connectivity and pattern diversity. We then showed how these parameters dissociate with ketamine and depend on intensity and site of stimulation. Our results support the idea that brief periods of activity-dependent neuronal silence can interrupt complex interactions in neocortical circuits, and open the way for further mechanistic investigations of the neuronal basis for consciousness and loss of consciousness across species.

Methotrexate injection for interstitial pregnancy: Hysteroscopic conservative mini-invasive approach.

BACKGROUND: Interstitial localisation of ectopic pregnancy is associated with high rates of maternal morbidity and mortality. Considering the rarity of interstitial pregnancy, the optimal treatment regimen remains unclear. We propose the management of interstitial pregnancy with local methotrexate injection using a combined hysteroscopic and ultrasonographic approach. TECHNIQUE: Hysteroscopy was performed under local anaesthesia in the operating room, using a 2.9-mm Hopkins II Forward-Oblique Telescope 30° endoscope with a 4.3-mm inner sheath and 5 FR instruments. A needle was pushed into the cornual region injecting methotrexate solution directly into the gestational sac and into the myometrial tissue tangentially at the four cardinal points. A contemporary transabdominal ultrasound (US) was performed in order to reduce risks of complications. EXPERIENCE: Five patients with an US diagnosis of interstitial ectopic pregnancy admitted to our department between January 2016 and September 2019 were managed with a local hysteroscopic injection of methotrexate. The technique was effective in all patients and no surgical complications occurred during or after the procedure. Three patients were evaluated for tubal patency with contrast ultrasonography confirming bilateral tubal patency 9 months from treatment, while one patient had a spontaneous birth 22 months from their initial surgery. CONCLUSION: The hysteroscopic ultrasound-guided approach combined with the local injection of methotrexate is a minimally invasive conservative approach that seems to be promising in the management of interstitial ectopic pregnancy.

Assessment of levator hiatal area using 3D/4D transperineal ultrasound in women with deep infiltrating endometriosis and superficial dyspareunia treated with pelvic floor muscle physiotherapy: randomized controlled trial.

OBJECTIVES: Deep infiltrating endometriosis (DIE) is associated with chronic pelvic pain, dyspareunia and pelvic floor muscle hypertonia. The primary aim of this study was to evaluate the effect of pelvic floor physiotherapy (PFP) on the area of levator ani hiatus during Valsalva maneuver, assessed using transperineal ultrasound, in women with DIE suffering from superficial dyspareunia. METHODS: This was a randomized controlled trial of 34 nulliparous women diagnosed with DIE and associated superficial dyspareunia. After an initial clinical examination, all patients underwent three-dimensional/four-dimensional (3D/4D) transperineal ultrasound to measure the levator hiatal area (LHA) at rest, on maximum pelvic floor muscle contraction and on maximum Valsalva maneuver, and were asked to rate their pain symptoms using a numerical rating scale (NRS). Eligible women were assigned randomly (1:1 ratio) to no intervention (control group, 17 women) or treatment with five individual sessions of PFP (study group, 17 women). Four months after the first examination, all women underwent a second evaluation of pain symptoms and LHA on transperineal ultrasound. The primary outcome measure was the percentage change in LHA on maximum Valsalva maneuver between the baseline and follow-up examinations. The percentage changes in pain symptoms between the two examinations, including superficial and deep dyspareunia, dysmenorrhea, chronic pelvic pain, dysuria and dyschezia, were also evaluated. RESULTS: Thirty women, comprising 17 in the study group and 13 in the control group, completed the study and were included in the analysis. The percentage change in LHA on maximum Valsalva maneuver between the two examinations was higher in the study group than in the control group (20.0 ± 24.8% vs -0.5 ± 3.3%; P = 0.02), indicating better pelvic floor muscle relaxation. After PFP treatment, the NRS score for superficial dyspareunia remained almost unchanged in the control group (median change in NRS (Δ-NRS), 0 (interquartile range (IQR), 0-0)) while a marked reduction was observed in the study group (median Δ-NRS, -3 (IQR, -4 to -2); P < 0.01). Moreover, there was a significant difference between the PFP and control groups with regards to the change in chronic pelvic pain (median Δ-NRS, 0 (IQR, -2 to 0) vs 0 (IQR, 0-1); P = 0.01). CONCLUSIONS: In women with DIE, PFP seems to result in increased LHA on Valsalva maneuver, as observed by 3D/4D transperineal ultrasound, leading to improved superficial dyspareunia, chronic pelvic pain and pelvic floor muscle relaxation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Autoimmune polyendocrine syndrome type 1 (APECED) in the Indian population: case report and review of a series of 45 patients.

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) or autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive genetic disease due to mutations in the AIRE (AutoImmune REgulator) gene. The clinical diagnosis is classically based on the presence of at least two of the three main components: chronic mucocutaneous candidiasis, hypoparathyroidism and primary adrenal insufficiency. Patients often suffer from other endocrine or non-endocrine autoimmune conditions throughout life. APECED etiopathogenesis is mediated by T lymphocytes. Autoantibodies against proteins of the affected organs are found in the serum of APECED patients as well as neutralizing antibodies against cytokines. We report here the clinical and genetic characteristics of 45 Indian APECED patients in comparison to Finnish, Sardinian, Turkish and North/South American cohorts from their published results. We also report a new case of APECED of Indian origin, a 2-year old child suffering from chronic mucocutaneous candidiasis since the age of 8 months, with confirmatory AIRE homozygous mutation c.274C > T (p.R92W). CONCLUSION: With the inherent limitations of a retrospective study, analysis of Indian APECED patients suggested that compared to classic criteria, application of Ferre/Lionakis criteria validated in North/South American patients could help in earlier diagnosis in 3 of 8 (37.5%) patients for whom adequate information for evaluation was available.

2D/3D accuracies of implant position after guided surgery using different surgical protocols: A retrospective study.

PURPOSE: To compare the 2D and 3D positional accuracy of four guided surgical protocols using an analysis of linear and angular deviations. METHODS: DICOM and .STLs files obtained from a CBCT and a digital impression were superimposed with software to plan implant position. Fifty-six patients were subdivided into 4 groups: FGA group (template support [Ts]: teeth [T]; bed preparation [Bp]: fully guided [FG]; implant insertion [Ii]: 3D template [3Dt]; device [D]: manual adapter [MA], FGM group (Ts: T; Bp: FG; Ii: 3Dt; D: fully guided mounter [FGM]), PG group (Ts: T; Bp: FG; Ii: manual; D: none) and MS group (Ts: mucosa; Bp: FG; Ii: 3Dt; D: FGM). The position of 120 implants was assessed by superimposing the planned and final position recorded with a digital impression. RESULTS: In FGA group, 3D deviations were 0.92 ± 0.52 mm at the implant head and 1.14 ± 0.54 mm at the apex, and the angular deviation (ang. dev.) was 2.45 ± 1.24°. In FGM group, were 0.911 ± 0.44 mm (head) and 1.11 ± 0.54 mm (apex), and the ang. dev. was 2.73 ± 1.96°. In PG group, were 0.95 ± 0.47 mm (head) and 1.17 ± 0.488 mm (apex), and the ang. dev. was 3.71 ± 1.67°. In MS group, were 1.15 ± 0.45 mm (head) and 1.42 ± 0.45 mm (apex), and the ang. dev. was 4.19 ± 2.62°. Ang. dev. of MS group was different from the other groups (P < 0.05). CONCLUSIONS: Guided surgery showed a sufficient accuracy.

Chronic activation of anti-oxidant pathways and iron accumulation in epileptogenic malformations.

AIMS: Oxidative stress is evident in resected epileptogenic brain tissue of patients with developmental brain malformations related to mammalian target of rapamycin activation: tuberous sclerosis complex (TSC) and focal cortical dysplasia type IIb (FCD IIb). Whether chronic activation of anti-oxidant pathways is beneficial or contributes to pathology is not clear. METHODS: We investigated oxidative stress markers, including haem oxygenase 1, ferritin and the inflammation associated microRNA-155 in surgically resected epileptogenic brain tissue of TSC (n = 10) and FCD IIb (n = 8) patients and in a TSC model (Tsc1GFAP-/- mice) using immunohistochemistry, in situ hybridization, real-time quantitative PCR and immunoblotting. Using human foetal astrocytes we performed an in vitro characterization of the anti-oxidant response to acute and chronic oxidative stress and evaluated overexpression of the disease-relevant pro-inflammatory microRNA-155. RESULTS: Resected TSC or FCD IIb tissue displayed higher expression of oxidative stress markers and microRNA-155. Tsc1GFAP-/- mice expressed more microRNA-155 and haem oxygenase 1 in the brain compared to wild-type, preceding the typical development of spontaneous seizures in these animals. In vitro, chronic microRNA-155 overexpression induced haem oxygenase 1, iron regulatory elements and increased susceptibility to oxidative stress. Overexpression of iron regulatory genes was also detected in patients with TSC, FCD IIb and Tsc1GFAP-/- mice. CONCLUSION: Our results demonstrate that early and sustained activation of anti-oxidant signalling and dysregulation of iron metabolism are a pathological hallmark of FCD IIb and TSC. Our findings suggest novel therapeutic strategies aimed at controlling the pathological link between both processes.

Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders.

HIV-associated neurocognitive disorders (HAND) have been linked to dysregulation of glutamate metabolism in the central nervous system (CNS) culminating in elevated extracellular glutamate and disrupted glutamatergic neurotransmission. Increased glutamate synthesis via upregulation of glutaminase (GLS) activity in brain immune cells has been identified as one potential source of excess glutamate in HAND. However, direct evidence for this hypothesis in an animal model is lacking, and the viability of GLS as a drug target has not been explored. In this brief report, we demonstrate that GLS inhibition with the glutamine analogue 6-diazo-5-oxo-L-norleucine (DON) can reverse cognitive impairment in the EcoHIV-infected mouse model of HAND. However, due to peripheral toxicity DON is not amenable to clinical use in a chronic disease such as HAND. We thus tested JHU083, a novel, brain penetrant DON prodrug predicted to exhibit improved tolerability. Systemic administration of JHU083 reversed cognitive impairment in EcoHIV-infected mice similarly to DON, and simultaneously normalized EcoHIV-induced increases in cerebrospinal fluid (CSF) glutamate and GLS activity in microglia-enriched brain CD11b + cells without observed toxicity. These studies support the mechanistic involvement of elevated microglial GLS activity in HAND pathogenesis, and identify JHU083 as a potential treatment option. Graphical Abstract Please provide Graphical Abstract caption.Glutamine Antagonist JHU083 Normalizes Aberrant Glutamate Production and Cognitive Deficits in the EcoHIV Murine Model of HIV-Associated Neurocognitive Disorders .

In vitro 3D and gravimetric analysis of removed tooth structure for complete and partial preparations.

PURPOSE: To quantify and to compare a gravimetric and three-dimensional (3D) analysis of the removed tooth structure for different complete crown preparations. METHODS: A total of 80 molar resin teeth and 8 preparation finishing lines were chosen: 1 for metal ceramic crowns (MCC); 3 for zirconia all-ceramic crowns: knife edge (ZirKnE), chamfer (ZirCha), and shoulder (ZirSho); 4 for lithium disilicate: light chamfer (LDLCha), chamfer (LDCha), shoulder (LDSho) and table top. Teeth were individually weighed to high precision and then prepared following the preparation guidelines. The teeth were reweighed after preparation, and the amount of structural reduction was calculated. In addition, all teeth were scanned before and after preparation, and the 3D volume of removed dental tissue was calculated, superimposing the two .stl files, as a difference of the volumes before and after the preparation. Kruskal-Wallis statistical analysis was carried out to determine significant differences among the groups with a significance level of p<0.05. RESULTS: Both analyses showed that LDLCha, ZirKnE and table-top preparations produced the smallest amount of removed structure, whereas the preparations for MCC, ZirSho and LDSho were more destructive. For MCC, 2.6 times more tooth structure must be removed than for table top. ZirKnE was 17.82% and LDLCha was 21.51% more conservative than MCC. The data obtained through the volumetric method were similar with those obtained by gravimetric analysis. CONCLUSIONS: ZirKnE, LDLCha, and table-top preparations produced the least amount of tooth tissue removal. Three-dimensional volumetric analysis can be a possible alternative to gravimetric analysis.

Influence of preparation design and spacing parameters on the risk of chipping of crowns made with Cerec Bluecam before cementation.

PURPOSE: To evaluate the influence of the preparation design and spacing parameters on the risk of chipping of crowns made by CEREC Bluecam before cementation. METHODS: A knife-edge preparation and a chamfer preparation were made on upper premolars. The teeth were scanned and two Co-Cr alloy replicas were made. Fifteen full crowns were manufactured for four groups using CEREC. The groups differed in type of preparation (knife-edge (KE) or chamfer (CHA)) and spacing parameters: spacer (0 or 150µm), marginal adhesive gap (10 or 50 or 150µm) and margin thickness (0 or 300µm). The four groups were: CHA 150 (spacer)- 50 (marginal adhesive gap)- 0 (margin thickness), KE 150-50-0, KE 150-50-300 and KE 150-150-300. The crowns were loaded before cementation by using an Instron machine to simulate the masticatory load applied during a trial. Differences in means were compared using two-way ANOVA and a post-hoc test (Tukey Test). The level of significance was set at P=0.05. RESULTS: The fracture values, ordered from least to most resistant, were: KE 150-50-300 group, CHA 150-50-0 group, KE 150-50-0 group and KE 150-150-300 group. Two-way ANOVA revealed statistically significant differences between pairs of means (p<0.05). Tukey's test showed that restorations of the KE 150-150-300 group can withstand a load significantly higher than that of other groups (p<0.01). In this group, the failures were mostly minor chippings, while the other groups had mostly major chippings and fractures. CONCLUSIONS: Marginal adhesive gap can affect the trial of a full crown.

Effects of rapamycin and curcumin on inflammation and oxidative stress in vitro and in vivo - in search of potential anti-epileptogenic strategies for temporal lobe epilepsy.

BACKGROUND: Previous studies in various rodent epilepsy models have suggested that mammalian target of rapamycin (mTOR) inhibition with rapamycin has anti-epileptogenic potential. Since treatment with rapamycin produces unwanted side effects, there is growing interest to study alternatives to rapamycin as anti-epileptogenic drugs. Therefore, we investigated curcumin, the main component of the natural spice turmeric. Curcumin is known to have anti-inflammatory and anti-oxidant effects and has been reported to inhibit the mTOR pathway. These properties make it a potential anti-epileptogenic compound and an alternative for rapamycin. METHODS: To study the anti-epileptogenic potential of curcumin compared to rapamycin, we first studied the effects of both compounds on mTOR activation, inflammation, and oxidative stress in vitro, using cell cultures of human fetal astrocytes and the neuronal cell line SH-SY5Y. Next, we investigated the effects of rapamycin and intracerebrally applied curcumin on status epilepticus (SE)-induced inflammation and oxidative stress in hippocampal tissue, during early stages of epileptogenesis in the post-electrical SE rat model for temporal lobe epilepsy (TLE). RESULTS: Rapamycin, but not curcumin, suppressed mTOR activation in cultured astrocytes. Instead, curcumin suppressed the mitogen-activated protein kinase (MAPK) pathway. Quantitative real-time PCR analysis revealed that curcumin, but not rapamycin, reduced the levels of inflammatory markers IL-6 and COX-2 in cultured astrocytes that were challenged with IL-1ß. In SH-SY5Y cells, curcumin reduced reactive oxygen species (ROS) levels, suggesting anti-oxidant effects. In the post-SE rat model, however, treatment with rapamycin or curcumin did not suppress the expression of inflammatory and oxidative stress markers 1 week after SE. CONCLUSIONS: These results indicate anti-inflammatory and anti-oxidant properties of curcumin, but not rapamycin, in vitro. Intracerebrally applied curcumin modified the MAPK pathway in vivo at 1 week after SE but failed to produce anti-inflammatory or anti-oxidant effects. Future studies should be directed to increasing the bioavailability of curcumin (or related compounds) in the brain to assess its anti-epileptogenic potential in vivo.

Acrocomia aculeata oil: Beneficial effects on cyclophosphamide-induced reproductive toxicity in male rats.

This study aimed to evaluate the effects of the extracted oil of Acrocomia aculeata pulp in preventing or mitigating the reproductive toxicity induced by cyclophosphamide (CP) in male rats. Adult male rats were segregated into seven groups that received vehicle, 100 mg/kg/day of CP, or 10 mg/kg/day of ß-carotene or 3 or 30 mg/kg/day of A. aculeata oil co-administered with CP. A. aculeata oil exhibited a high content of ß-carotene. CP treatment induced reproductive toxicity in the animals, as it changed the reproductive organs weight, hormone levels, sperm counts and testicular histology. In contrast, co-administration of A. aculeata improved CP-induced alterations in these parameters. A. aculeata oil also increased the gene Ckit expression and normalised the antioxidant enzymes levels which were changed by CP. The A. aculeata oil is capable of protecting the male reproductive system from the adverse effects of CP, possibly by acting as an antioxidant and increasing the Ckit gene expression.

Pharmacokinetics of Intranasal versus Subcutaneous Insulin in the Mouse.

Insulin delivery to the brain has emerged as an important therapeutic target for cognitive disorders associated with abnormal brain energy metabolism. Although insulin is transported across the blood-brain barrier, peripheral routes of administration are problematic due to systemic effects of insulin on blood glucose. Intranasal (IN) administration is being investigated as an alternative route. We conducted a head-to-head comparison of subcutaneous (SC) and IN insulin, assessing plasma and brain pharmacokinetics and blood glucose levels in the mouse. SC insulin (2.4 IU) achieved therapeutically relevant concentrations in the brain (AUCbrain = 2537 h·µIU/mL) but dramatically increased plasma insulin (AUCplasma = 520 351 h·*µIU/mL), resulting in severe hypoglycemia and in some cases death. IN administration of the same dose resulted in similar insulin levels in the brain (AUCbrain = 3442 h·µIU/mL) but substantially lower plasma concentrations (AUCplasma = 354 h·µIU/mL), amounting to a ∼ 2000-fold increase in the AUCbrain:plasma ratio relative to SC. IN dosing also had no significant effect on blood glucose. When administered daily for 9 days, IN insulin increased brain glucose and energy metabolite concentrations (e.g., adenosine triphosphate and phosphocreatine) without causing overt toxicity, suggesting that IN insulin may be a safe therapeutic option for cognitively impaired patients.

Pelvic floor muscle assessment on three- and four-dimensional transperineal ultrasound in women with ovarian endometriosis with or without retroperitoneal infiltration: a step towards complete functional assessment.

OBJECTIVES: Previous studies comparing women with deep infiltrating endometriosis (DIE) and healthy controls have underlined an association between pelvic floor muscle (PFM) hypertonic dysfunction and deep lesions. The aim of this study was to compare the morphometry of PFM in women affected by ovarian endometriosis with DIE vs those without DIE in order to assess the impact of retroperitoneal infiltration by the disease on PFM function. METHODS: This was a prospective study conducted between March 2015 and December 2016 on symptomatic women with a clinical and sonographic diagnosis of ovarian endometriosis with or without DIE, scheduled for laparoscopic surgery. We excluded patients with current or previous pregnancy, previous surgery for deep endometriosis, other causes of chronic pelvic pain or congenital or acquired abnormalities of pelvic floor anatomy. Three- and four-dimensional transperineal ultrasound was performed to evaluate PFM morphometry and assess levator hiatal area (LHA) and diameters at rest, during PFM contraction and during Valsalva maneuver. All volumes were analyzed offline by an investigator blinded to the clinical data. RESULTS: One hundred and fourteen patients with ovarian endometriosis were enrolled in the study, 75 with DIE and 39 without DIE. The diagnosis of endometriosis was confirmed by histological examination in all patients. Compared with women without DIE, women with DIE showed a smaller LHA at rest, during contraction and during Valsalva maneuver (P = 0.03, P = 0.03 and P = 0.02, respectively) and a smaller reduction in LHA during PFM contraction (P = 0.04). CONCLUSIONS: Women with ovarian endometriosis who were affected by DIE showed smaller hiatal dimensions than did women without DIE. Considering that PFM dysfunction in patients with DIE could cause pain symptoms and pelvic organ dysfunction, transperineal ultrasound could allow a more complete functional assessment and tailored therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Jaccoud's arthropathy, an unusual manifestation of idiopathic retroperitoneal fibrosis: rapid improvement of symptoms after tocilizumab treatment.

Jaccoud's arthropathy (JA) is a chronic, non erosive, rheumatoid-like deformity associated with rheumatic fever (RF) and systemic lupus erythematosus and with other diseases such as psoriatic arthritis, connective tissue diseases, hypocomplementemic urticarial vasculitis, infections, sarcoidosis and neoplasia. We described a case of JA in a patient with cutaneous psoriasis but with a particular disease evolution associated with idiopathic retropritoneal fibrosis (IRF), evaluated with computed tomography, magnetic resonance and 18F-FDG PET/ CT. The patient, following failure with steroids, methotrexate and etanercept, was treated with tocilizumab (8 mg/kg) once every 4 weeks for 6 months. A rapid improvement of symptoms and disappearance of 18F-FDG uptake was shown. We describe a review of literature of rheumatic manifestations of IRF and the possible role of interleukin-6 in the pathway of JA and IRF.

Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease.

BACKGROUND: miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD). METHODS: The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice. CONCLUSION: These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.