The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: Implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment are lacking. We asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound (CDDO-EA) mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: (1) location discrimination reversal (tests behavior pattern separation and cognitive flexibility, abilities reliant on the dentate gyrus) and (2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment's end (14.25-month post-IRR), an index relevant to neurogenesis was quantified (doublecortin-immunoreactive [DCX+] dentate gyrus immature neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. One radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had slower stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice showed normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change relevant to neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

Investigating the Impact of Intracerebroventricular Streptozotocin on Female Rats with and without Ovaries: Implications for Alzheimer's Disease.

To contribute to research on female models of Alzheimer's disease (AD), our aim was to study the effect of intracerebroventricular (ICV) injection of streptozotocin (STZ) in female rats, and to evaluate a potential neuroprotective action of ovarian steroids against STZ. Female rats were either ovariectomized (OVX) or kept with ovaries (Sham) two weeks before ICV injections. Animals were injected with either vehicle (artificial cerebrospinal fluid, aCSF) or STZ (3 mg/kg) and separated into four experimental groups: Sham + aCSF, Sham + STZ, OVX + aCSF and OVX + STZ. Nineteen days post-injection, we assessed different behavioral aspects: burying, anxiety and exploration, object recognition memory, spatial memory, and depressive-like behavior. Immunohistochemistry and Immunoblot analyses were performed in the hippocampus to examine changes in AD-related proteins and neuronal and microglial populations. STZ affected burying and exploratory behavior depending on ovarian status, and impaired recognition but not spatial memory. STZ and ovariectomy increased depressive-like behavior. Interestingly, STZ did not alter the expression of ß-amyloid peptide or Tau phosphorylated forms. STZ affected the neuronal population from the Dentate Gyrus, where immature neurons were more vulnerable to STZ in OVX rats. Regarding microglia, STZ increased reactive cells, and the OVX + STZ group showed an increase in the total cell number. In sum, STZ partially affected female rats, compared to what was previously reported for males. Although AD is more frequent in women, reports about the effect of ICV-STZ in female rats are scarce. Our work highlights the need to deepen into the effects of STZ in the female brain and study possible sex differences.

Chemical composition and studying the possible neuroprotective effect of iridoids-rich fraction from Pentas lanceolata leaves using rotenone model of Parkinson's disease in mice.

Parkinsonism is an age-related neurodegenerative illness that affects motor coordination leading to loss of dopaminergic neurons. Many medications are used for the treatment of Parkinson's disease but are only symptomatic and have a limited effect on the progression of this ailment. Therefore, bioactive compounds which derived from plants have been examined for their ability to improve the neuronal damage and cell death happened in parkinsonian patients. In this study the iridoids-rich fraction isolated from Pentas lanceolata (PIRF) leaves was investigated for its phytoconstituents. Seven iridoids (1-7) and one flavonol diglycoside (8) were isolated, and their chemical structures were achieved by 1H and 13C nuclear magnetic resonance and ESI-MS spectral data. Compound 1 (6ß,7ß-epoxy-8-epi-splendoside) and 5 (gaertneroside) were isolated for the first time from Pentas genus as well as compound 8 (kaempferol-3-O-robinobioside). The current study aims to investigate the possible anti-parkinsonian effect of PIRF using a rotenone model of Parkinsonism in mice. Behavioural tests (wirehanging, stair and wooden-walking tests) were done to examine the motor coordination in mice after treatment. Biochemical and histopathological examinations for brain striatum in different groups were also evaluated. Results revealed that rotenone-treated mice had poor motor functions described by depletion of dopamine and Ach levels, a significant increase in proinflammatory cytokines, IL-1B, TNF-α and Mcp-1 and oxidative biomarkers with subsequent reduction in antioxidant mediators. Disorganization of striatum, degenerated neurocytes, slight vacuolation, shrunken neurons with pyknotic nuclei and apoptotic cells are displayed by histopathological examinations. Treatment with PIRF ameliorates the neurodegeneration-induced by rotenone in the brain of mice. The anti-parkinsonian effect of PIRF could be attributed to their bioactive constituents of iridoids.

Development and In vivo Evaluation of Atomoxetine Hydrochloride ODMTs in a Nicotine-induced Attention Deficit Hyperactivity Disorder (ADHD) Model in Rats.

The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with ß-cyclodextrin (ß-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-ß-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-ß-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development.

Experimental Model of Cerebral Arterial Air Embolism in Conscious Rats.

In this work, an optimal air supply mode was selected to create a model of cerebral arterial air embolism (CAAE) on conscious male Sprague-Dawley rats (n=49). The efficacy of the selected model (administration of 100 µl/kg of air at a rate of 10 µl/min with an infusion pump) was determined by changes in serum biochemical parameters (cholesterol, alkaline phosphatase, inorganic phosphates, AST, and triglycerides), impaired motor functions in the Rotarod test, and visual assessment of the ischemic foci (staining of frontal sections with 1% triphenyltetrazolium chloride solution) at different terms after AAE. The model of AAE created by us confirmed impairment of coordination and motor function in conscious animals and reproduced the lethal consequences of this condition. The obtained results can serve as the basis for drug testing and the development of new approaches to the treatment of ischemic stroke.

Modeling of Cerebral Ischemic Stroke in Conscious Rats via Arterial Air Embolization.

The etiological factor of cerebral ischemia in the vast majority of cases is vascular embolism. In the present study we investigated embolism caused by atmospheric air bubbles injected into the internal carotid artery of conscious rats. Immediately after embolism modeling, behavioral abnormalities were observed in the animals, and after 24 h, foci of brain damage were detected. The death of animals was observed within 5 days after embolism. The proposed experimental model of cerebral ischemia in conscious rats is more relevant and better corresponds to real conditions than the model on narcotized animals and allows to perform physiological tests immediately after modeling.

Behavioral and functional assessment of mice inner ear after chronic exposure to an ultrahigh B0 field of 11.7 T or 17.2 T.

PURPOSE: Assess short-term and long-term effects of chronic exposure to an ultrahigh static magnetic (B0 ) field on mice inner ear in the context of MR safety of human scanning at 11.7 T. METHODS: Mice were chronically exposed to a B0 field of 11.7 T or 17.2 T during ten 2-h exposure sessions evenly distributed over a period of 5 weeks, resulting in a total of 20 h of exposure per mouse. During exposure sessions, mice were anesthetized and positioned either parallel or antiparallel to B0 . Before, during, and 2 weeks after the magnetic-field exposure period, mice performed behavioral tests (balance beam, rotarod, and swim tests) to evaluate their short-term and long-term motor coordination and balance. An auditory brainstem response (ABR) test was finally performed to assess the functional integrity of mice cochlea, 2 weeks after the last exposure. RESULTS: After awaking from anesthesia following B0 exposures at 11.7 Tor 17.2 T, mice displayed a transient (<5 min) rotating behavior. The behavioral tests did not show any difference between the exposed and the control mice at any time point. Determination of ABR thresholds did not reveal an impairment of cochlea hair cells resulting from chronic B0 exposure. CONCLUSION: Despite the transient disturbance of mice vestibular system observed immediately after B0 exposure, no short-term nor long-term alteration was detected with behavioral and ABR tests.

Zebrafish, a biological model for pharmaceutical research for the management of anxiety.

The zebrafish (Danio rerio) is a valuable animal model rapidly becoming more commonly used in pharmaceutical studies. Due to its low-cost maintenance and high breeding potential, the zebrafish is a suitable substitute for most adult rodents (mice and rats) in neuroscience research. It is widely used in various anxiety models. This species has been used to develop a conceptual framework for anxiety behavior studies with broad applications in the laboratory, including the study of herbal and chemical drugs. This review discusses the latest studies of anxiety-related behavior in the zebrafish model.

Deep learning-based behavioral profiling of rodent stroke recovery.

BACKGROUND: Stroke research heavily relies on rodent behavior when assessing underlying disease mechanisms and treatment efficacy. Although functional motor recovery is considered the primary targeted outcome, tests in rodents are still poorly reproducible and often unsuitable for unraveling the complex behavior after injury. RESULTS: Here, we provide a comprehensive 3D gait analysis of mice after focal cerebral ischemia based on the new deep learning-based software (DeepLabCut, DLC) that only requires basic behavioral equipment. We demonstrate a high precision 3D tracking of 10 body parts (including all relevant joints and reference landmarks) in several mouse strains. Building on this rigor motion tracking, a comprehensive post-analysis (with >100 parameters) unveils biologically relevant differences in locomotor profiles after a stroke over a time course of 3 weeks. We further refine the widely used ladder rung test using deep learning and compare its performance to human annotators. The generated DLC-assisted tests were then benchmarked to five widely used conventional behavioral set-ups (neurological scoring, rotarod, ladder rung walk, cylinder test, and single-pellet grasping) regarding sensitivity, accuracy, time use, and costs. CONCLUSIONS: We conclude that deep learning-based motion tracking with comprehensive post-analysis provides accurate and sensitive data to describe the complex recovery of rodents following a stroke. The experimental set-up and analysis can also benefit a range of other neurological injuries that affect locomotion.

PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE. Diabetic C57BL/6 mice were treated with PARIN5, a novel PAR1 modulator. Behavioral changes in the open field and novel object recognition tests, serum neurofilament (NfL) levels and thrombin activity in central and peripheral nervous system tissue (CNS and PNS, respectively), brain mRNA expression of tumor necrosis factor α (TNF-α), Factor X (FX), prothrombin, and PAR1 were assessed. Subtle behavioral changes were detected in diabetic mice. These were accompanied by an increase in serum NfL, an increase in central and peripheral neural tissue thrombin activity, and TNF-α, FX, and prothrombin brain intrinsic mRNA expression. Systemic treatment with PARIN5 prevented the appearance of behavioral changes, normalized serum NfL and prevented the increase in peripheral but not central thrombin activity. PARIN5 treatment prevented the elevation of both TNF-α and FX but significantly elevated prothrombin expression. PARIN5 treatment prevents behavioral and neural damage in the DE model, suggesting it for future clinical research.

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer's Disease Mice Model.

Alzheimer's disease (AD) is one of the most widespread neurodegenerative diseases. Most of the current AD therapeutic developments are directed towards improving neuronal cell function or facilitating Aß amyloid clearance from the brain. However, some recent evidence suggests that astrocytes may play a significant role in the pathogenesis of AD. In this paper, we evaluated the effects of the optogenetic activation of Gq-coupled exogenous receptors expressed in astrocytes as a possible way of restoring brain function in the AD mouse model. We evaluated the effects of the optogenetic activation of astrocytes on long-term potentiation, spinal morphology and behavioral readouts in 5xFAD mouse model of AD. We determined that in vivo chronic activation of astrocytes resulted in the preservation of spine density, increased mushroom spine survival, and improved performance in cognitive behavioral tests. Furthermore, chronic optogenetic stimulation of astrocytes resulted in the elevation of EAAT-2 glutamate uptake transporter expression, which could be a possible explanation for the observed in vivo neuroprotective effects. The obtained results suggest that the persistent activation of astrocytes may be considered a potential therapeutic approach for the treatment of AD and possibly other neurodegenerative disorders.

Application of Behavioral Tests for Evaluation of an Experimental Model of Alzheimer's Disease in Female Rats.

Alzheimer's disease was modeled in female Wistar rats aged 4 months by stereotaxic bilateral injection of a synthetic peptide ß-amyloid (Aß1-42) into the hippocampus. Behavioral tests (open field, Y-maze, passive avoidance, and Morris water maze) revealed significant impairment of memory and spatial navigation 8 weeks after ß-amyloid administration. At this term, the cognitive impairments typical of Alzheimer's disease are reproduced. The experimental model of Alzheimer's disease proposed by us can be used in preclinical studies of drugs for the treatment of this pathology.

The Anti-Depressive Effects of Ultra-High Static Magnetic Field.

BACKGROUND: Ultra-high field magnetic resonance imaging (MRI) has obvious advantages in acquiring high-resolution images. 7 T MRI has been clinically approved and 21.1 T MRI has also been tested on rodents. PURPOSE: To examine the effects of ultra-high field on mice behavior and neuron activity. STUDY TYPE: Prospective, animal model. ANIMAL MODEL: Ninety-eight healthy C57BL/6 mice and 18 depression model mice. FIELD STRENGTH: 11.1-33.0 T SMF (static magnetic field) for 1 hour and 7 T for 8 hours. Gradients were not on and no imaging sequence was used. ASSESSMENT: Open field test, elevated plus maze, three-chambered social test, Morris water maze, tail suspension test, sucrose preference test, blood routine, biochemistry examinations, enzyme-linked immunosorbent assay, immunofluorescent assay. STATISTICAL TESTS: The normality of the data was assessed by Shapiro-Wilk test, followed by Student's t test or the Mann-Whitney U test for statistical significance. The statistical cut-off line is P < 0.05. RESULTS: Compared to the sham group, healthy C57/6 mice spent more time in the center area (35.12 ± 4.034, increased by 47.19%) in open field test and improved novel index (0.6201 ± 0.02522, increased by 16.76%) in three-chambered social test a few weeks after 1 hour 11.1-33.0 T SMF exposure. 7 T SMF exposure for 8 hours alleviated the depression state of depression mice, including less immobile time in tail suspension test (58.32% reduction) and higher sucrose preference (increased by 8.80%). Brain tissue analysis shows that 11.1-33.0 T and 7 T SMFs can increase oxytocin by 164.65% and 36.03%, respectively. Moreover, the c-Fos level in hippocampus region was increased by 14.79%. DATA CONCLUSION: 11.1-33.0 T SMFs exposure for 1 hour or 7 T SMF exposure for 8 hours did not have detrimental effects on healthy or depressed mice. Instead, these ultra-high field SMFs have anti-depressive potentials. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Antidepressant effects of cherry leaf decoction on a chronic unpredictable mild stress rat model based on the Glu/GABA-Gln metabolic loop.

Cherry leaves (Prunus pseudocerasus Lindl. [Rosaceae]), a traditional Chinese herbal medicine, can regulate the factors closely related to depression including inflammatory cytokines, oxidative stress and blood glucose level. However, the antidepressant effects of cherry leaves and underlying neuromodulatory mechanisms remain relatively have not been elucidated explicitly. The present study investigated the antidepressant effects of cherry leaf decoction (CLD). The underlying neuromodulatory mechanism was explored by examining the glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. The chronic unpredictable mild stress (CUMS) rodent model was used in this study. The main flavonoids components of CLD were identified using high-performance liquid chromatography (HPLC). The antidepressant effects of CLD were assessed throughout behavioural tests including the bodyweight, sucrose preference test (SPT), forced swimming test (FPT) and tail suspension test (TST). Moreover, The baseline levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. The expression of proteins integrally involved in the Glu/GABA-Gln metabolic loop were observed and quantified by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. This study found that CLD ameliorated depressive-like behaviours induced by CUMS. The increase of serum ACTH and CORT baseline levels induced by CUMS was also reversed after CLD intervention. Furthermore, CUMS reduced the expression of GAD65, GAD67, GLT-1, GS and GABAA and increased NMDAR1 levels in the rat hippocampus, which was normalized by CLD treatment. The findings demonstrated that CLD could ameliorate the depression-like behaviours induced by CUMS, potentially through the inhibition of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and the regulation of Glu/GABA-Gln metabolic loop.

Effect of Cardiotonic Steroid Marinobufagenin on Vascular Remodeling and Cognitive Impairment in Young Dahl-S Rats.

The hypertensive response in Dahl salt-sensitive (DSS) rats on a high-salt (HS) diet is accompanied by central arterial stiffening (CAS), a risk factor for dementia, and heightened levels of a prohypertensive and profibrotic factor, the endogenous Na/K-ATPase inhibitor marinobufagenin (MBG). We studied the effect of the in vivo administration of MBG or HS diet on blood pressure (BP), CAS, and behavioral function in young DSS rats and normotensive Sprague-Dawley rats (SD), the genetic background for DSS rats. Eight-week-old male SD and DSS rats were given an HS diet (8% NaCl, n = 18/group) or a low-salt diet (LS; 0.1% NaCl, n = 14-18/group) for 8 weeks or MBG (50 µg/kg/day, n = 15-18/group) administered via osmotic minipumps for 4 weeks in the presence of the LS diet. The MBG-treated groups received the LS diet. The systolic BP (SBP); the aortic pulse wave velocity (aPWV), a marker of CAS; MBG levels; spatial memory, measured by a water maze task; and tissue collection for the histochemical analysis were assessed at the end of the experiment. DSS-LS rats had higher SBP, higher aPWV, and poorer spatial memory than SD-LS rats. The administration of stressors HS and MBG increased aPWV, SBP, and aortic wall collagen abundance in both strains vs. their LS controls. In SD rats, HS or MBG administration did not affect heart parameters, as assessed by ECHO vs. the SD-LS control. In DSS rats, impaired whole-heart structure and function were observed after HS diet administration in DSS-HS vs. DSS-LS rats. MBG treatment did not affect the ECHO parameters in DSS-MBG vs. DSS-LS rats. The HS diet led to an increase in endogenous plasma and urine MBG levels in both SD and DSS groups. Thus, the prohypertensive and profibrotic effect of HS diet might be partially attributed to an increase in MBG. The prohypertensive and profibrotic functions of MBG were pronounced in both DSS and SD rats, although quantitative PCR revealed that different profiles of profibrotic genes in DSS and SD rats was activated after MBG or HS administration. Spatial memory was not affected by HS diet or MBG treatment in either SD or DSS rats. Impaired cognitive function was associated with higher BP, CAS, and cardiovascular remodeling in young DSS-LS rats, as compared to young SD-LS rats. MBG and HS had similar effects on the cardiovascular system and its function in DSS and SD rats, although the rate of change in SD rats was lower than in DSS rats. The absence of a cumulative effect of increased aPWV and BP on spatial memory can be explained by the cerebrovascular and brain plasticity in young rats, which help the animals to tolerate CAS elevated by HS and MBG and to counterbalance the profibrotic effect of heightened MBG.

The Effect of a New N-hetero Cycle Derivative on Behavior and Inflammation against the Background of Ischemic Stroke.

Ischemic stroke triggers a whole cascade of pathological changes in the brain, one of which is postischemic inflammation. Since in such cases thrombolytic therapy is often not possible, methods that modulate inflammation and affect microglia become particularly interesting. We synthesized 3-(2-oxo-4-phenylpyrrolidin-1-yl)propane-1-sulfonate calcium(II) (Compound 4) and studied its anti-inflammatory activity in in vitro and in vivo models of inflammation and ischemia. Macrophage cell line RAW 264.7 was treated with lipopolysaccharides (LPS) and Compound 4 at various dosages to study the cytokine profile using real-time PCR and cytometric bead array (CBA). Stroke in rats was simulated by the middle cerebral artery occlusion method (MCAO). Several tests were performed to characterize the neurological deficit and locomotor activity of the rats, and afterwards, postmortem, the number of astrocytes was counted using immunohistochemistry. Compound 4 in in vitro tests dose-dependently reduced the expression of interleukin-1ß (IL1ß), and inducible nitric oxide synthase (iNOS) genes in cell culture and increased the concentration of cytokines: interleukin-2, 4, 6 (IL-2, IL-4, and IL-6). In vivo Compound 4 increased the orienting-exploratory behavior, and reduced neurological and motor deficit. The number of astrocytes that promote and support inflammation was lower in the group treated with Compound 4. The stroke volume measured by magnetic resonance imaging (MRI) showed no difference. We have shown that Compound 4 demonstrates anti-inflammatory activity by increasing the synthesis of anti-inflammatory and reducing pro-inflammatory cytokines, and positively affects the neurological deficit in rats. Thus, Compound 4 has a high therapeutic potential in the management of patients after a stroke and requires further study of its neuroprotective properties.

Long-term behavioral effects observed in mice chronically exposed to static ultra-high magnetic fields.

PURPOSE: The primary goal of this study was to investigate whether chronic exposures to ultra-high B0 fields can induce long-term cognitive, behavioral, or biological changes in C57BL/6 mice. METHODS: C57BL/6 mice were chronically exposed to 10.5-T or 16.4-T magnetic fields (3-h exposures, two exposure sessions per week, 4 or 8 weeks of exposure). In vivo single-voxel 1 H magnetic resonance spectroscopy was used to investigate possible neurochemical changes in the hippocampus. In addition, a battery of behavioral tests, including the Morris water-maze, balance-beam, rotarod, and fear-conditioning tests, were used to examine long-term changes induced by B0 exposures. RESULTS: Hippocampal neurochemical profile, cognitive, and basic motor functions were not impaired by chronic magnetic field exposures. However, the balance-beam-walking test and the Morris water-maze testing revealed B0 -induced changes in motor coordination and balance. The tight-circling locomotor behavior during Morris water-maze tests was found as the most sensitive factor indexing B0 -induced changes. Long-term behavioral changes were observed days or even weeks subsequent to the last B0 exposure at 16.4 T but not at 10.5 T. Fast motion of mice in and out of the 16.4-T magnet was not sufficient to induce such changes. CONCLUSION: Observed results suggest that the chronic exposure to a magnetic field as high as 16.4 T may result in long-term impairment of the vestibular system in mice. Although observation of mice may not directly translate to humans, nevertheless, they indicate that studies focused on human safety at very high magnetic fields are necessary.

Auditory processing disorder in children: the value of a multidisciplinary assessment.

PURPOSE: Auditory processing disorder (APD) may affect 0.2-5% of the paediatric population. The diagnosis of APD remains difficult because of polymorphic symptoms possibly entangled with other difficulties. The purpose of this study was to evaluate a new multi-disciplinary assessment in the French language. METHODS: The battery of tests was composed of: (a) APD targeted speech assessment: speech perception in noise, a dichotic test, temporal processing tests (patterns); (b) Psychometric assessment: sustained auditory attention, sustained visual attention, evaluation of cognitive functions; (c) phonemic identification and discrimination; (d) ENT examination, tonal and vocal audiometry and ABR recordings. The diagnosis was made if two of the targeted speech tests were 2 standard deviations (SDs) below the mean or if only one of the tests was 3 SDs below. The auditory attention tests, as well as the phonemic identification and discrimination tests were complementary to the diagnostic battery. However, they did not allow for the diagnosis of APD. RESULTS: 50 children suspected of APD benefited from this protocol, and 12 were excluded from the study. A diagnosis of APD was confirmed in 17 children (45%). 59% of the patients had associated disorders. The most effective tests for diagnosing APD were dichotic testing (p = 0.001) and pattern recognition (frequency, p = 0.001). The sustained auditory attention test (p = 0.01) and the phonemic identification and discrimination test reinforced the diagnosis of APD. CONCLUSION: It seems important to evaluate children suspected of APD with a multi-disciplinary protocol. It makes it possible to diagnose APD children, but also to identify attentional difficulties and cognitive disorders that may be associated.

Design, synthesis, and pharmacological characterization of some 2-substituted-3-phenyl-quinazolin-4(3H)-one derivatives as phosphodiesterase inhibitors.

Some 3-phenyl-quinazolin-4(3H)-one-2-thioethers (3a-e, 5a,b, 7a-e, 9a-d, 10a-d, and 12) along with 2-aminoquinazoline derivatives 13a-c were prepared and screened for their in vitro phosphodiesterase (PDE) inhibitory activity. Some compounds such as 7d,e, 9a,b,d, 10a,d, and 13b exhibited promising activity as compared with the non-selective PDE inhibitor IBMX. This inhibitory activity was validated by molecular docking in the active site of PDE7A and PDE4 to investigate their selectivity. Furthermore, the most active compound 10d (IC50 = 1.15 µM) was tested in vivo using behavioral tests. Compound 10d was able to pass the blood-brain barrier and improve scopolamine-induced cognitive deficits. Therefore, this core can be considered as a promising scaffold for further optimization to obtain new compounds with better PDE7A selective inhibition.

PEAß Triggers Cognitive Decline and Amyloid Burden in a Novel Mouse Model of Alzheimer's Disease.

Understanding the physiopathology of Alzheimer's disease (AD) has improved substantially based on studies of mouse models mimicking at least one aspect of the disease. Many transgenic lines have been established, leading to amyloidosis but lacking neurodegeneration. The aim of the current study was to generate a novel mouse model that develops neuritic plaques containing the aggressive pyroglutamate modified amyloid-ß (pEAß) species in the brain. The TAPS line was developed by intercrossing of the pEAß-producing TBA2.1 mice with the plaque-developing line APPswe/PS1ΔE9. The phenotype of the new mouse line was characterized using immunostaining, and different cognitive and general behavioral tests. In comparison to the parental lines, TAPS animals developed an earlier onset of pathology and increased plaque load, including striatal pEAß-positive neuritic plaques, and enhanced neuroinflammation. In addition to abnormalities in general behavior, locomotion, and exploratory behavior, TAPS mice displayed cognitive deficits in a variety of tests that were most pronounced in the fear conditioning paradigm and in spatial learning in comparison to the parental lines. In conclusion, the combination of a pEAß- and a plaque-developing mouse model led to an accelerated amyloid pathology and cognitive decline in TAPS mice, qualifying this line as a novel amyloidosis model for future studies.