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The aim of this study was to investigate the effect of rosuvastatin treatment on memory impairment, and anxiogenic-like effects in mice chronically infected with Toxoplasma gondii. For this, Balb/c mice were infected orally with chronic ME-49 strain of Toxoplasma gondii. Oral treatment with rosuvastatin (40mg/kg/day) started on the 51st day post-infection and was performed daily for 21 days. After completion of treatment, anxiety-like effects and locomotion were investigated in the open field (OF) test, whereas novel object recognition (NOR) test was used for evaluation of short- and long-term memory. At the end of the experiments, the brain was collected for Toxoplasma gondii DNA quantification and histopathological analysis. Infection with ME-49 strain decreased the time spent in the center of OF, indicating an anxiogenic effect, without affecting total and peripheral locomotion. Rosuvastatin treatment inhibited the change in the center time. Besides, pharmacological treatment increased total and central locomotion in both non-infected and infected animals. Infection also impaired both short- and long-term memory in the NOR test, and these effects were reverted by rosuvastatin treatment. In addition to effects in behavioral changes, rosuvastatin also reduced parasite load in the brain and attenuated signs of brain inflammation such as perivascular cuffs, inflammatory cell infiltration and tissue damage. These findings indicate for the first time the efficacy of rosuvastatin in treatment of memory impairment and anxiogenic effect evoked by infection with Toxoplasma gondii. These effects might be mediated by reduced cyst load, which in turn decrease inflammation and damage in the brain.

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Short- and Long-Term Changes in Joint Co-Contraction Associated With Motor Learning as Revealed From Surface EMG

Journal of Neurophysiology ◽

10.1152/jn.2002.88.2.991 ◽

2002 ◽

Vol 88 (2) ◽

pp. 991-1004 ◽

Cited By ~ 229

Author(s):

Rieko Osu ◽

David W. Franklin ◽

Hiroko Kato ◽

Hiroaki Gomi ◽

Kazuhisa Domen ◽

...

Keyword(s):

Surface Emg ◽

Internal Models ◽

Series Data ◽

Time Step ◽

Cross Correlation Analysis ◽

Performance Error ◽

Short And Long Term ◽

And Performance ◽

The Brain

In the field of motor control, two hypotheses have been controversial: whether the brain acquires internal models that generate accurate motor commands, or whether the brain avoids this by using the viscoelasticity of musculoskeletal system. Recent observations on relatively low stiffness during trained movements support the existence of internal models. However, no study has revealed the decrease in viscoelasticity associated with learning that would imply improvement of internal models as well as synergy between the two hypothetical mechanisms. Previously observed decreases in electromyogram (EMG) might have other explanations, such as trajectory modifications that reduce joint torques. To circumvent such complications, we required strict trajectory control and examined only successful trials having identical trajectory and torque profiles. Subjects were asked to perform a hand movement in unison with a target moving along a specified and unusual trajectory, with shoulder and elbow in the horizontal plane at the shoulder level. To evaluate joint viscoelasticity during the learning of this movement, we proposed an index of muscle co-contraction around the joint (IMCJ). The IMCJ was defined as the summation of the absolute values of antagonistic muscle torques around the joint and computed from the linear relation between surface EMG and joint torque. The IMCJ during isometric contraction, as well as during movements, was confirmed to correlate well with joint stiffness estimated using the conventional method, i.e., applying mechanical perturbations. Accordingly, the IMCJ during the learning of the movement was computed for each joint of each trial using estimated EMG-torque relationship. At the same time, the performance error for each trial was specified as the root mean square of the distance between the target and hand at each time step over the entire trajectory. The time-series data of IMCJ and performance error were decomposed into long-term components that showed decreases in IMCJ in accordance with learning with little change in the trajectory and short-term interactions between the IMCJ and performance error. A cross-correlation analysis and impulse responses both suggested that higher IMCJs follow poor performances, and lower IMCJs follow good performances within a few successive trials. Our results support the hypothesis that viscoelasticity contributes more when internal models are inaccurate, while internal models contribute more after the completion of learning. It is demonstrated that the CNS regulates viscoelasticity on a short- and long-term basis depending on performance error and finally acquires smooth and accurate movements while maintaining stability during the entire learning process.

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Brain imaging and human nutrition: which measures to use in intervention studies?

British Journal Of Nutrition ◽

10.1017/s0007114513001384 ◽

2013 ◽

Vol 110 (S1) ◽

pp. S1-S30 ◽

Cited By ~ 14

Author(s):

Stéphane V. Sizonenko ◽

Claudio Babiloni ◽

Eveline A. de Bruin ◽

Elizabeth B. Isaacs ◽

Lena S. Jönsson ◽

...

Keyword(s):

Brain Imaging ◽

Intervention Studies ◽

Resonance Spectroscopy ◽

Nutritional Interventions ◽

Imaging Technologies ◽

Short And Long Term ◽

Imaging Markers ◽

Nutritional Studies ◽

The Brain

The present review describes brain imaging technologies that can be used to assess the effects of nutritional interventions in human subjects. Specifically, we summarise the biological relevance of their outcome measures, practical use and feasibility, and recommended use in short- and long-term nutritional studies. The brain imaging technologies described consist of MRI, including diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI, as well as electroencephalography/magnetoencephalography, near-IR spectroscopy, positron emission tomography and single-photon emission computerised tomography. In nutritional interventions and across the lifespan, brain imaging can detect macro- and microstructural, functional, electrophysiological and metabolic changes linked to broader functional outcomes, such as cognition. Imaging markers can be considered as specific for one or several brain processes and as surrogate instrumental endpoints that may provide sensitive measures of short- and long-term effects. For the majority of imaging measures, little information is available regarding their correlation with functional endpoints in healthy subjects; therefore, imaging markers generally cannot replace clinical endpoints that reflect the overall capacity of the brain to behaviourally respond to specific situations and stimuli. The principal added value of brain imaging measures for human nutritional intervention studies is their ability to provide uniquein vivoinformation on the working mechanism of an intervention in hypothesis-driven research. Selection of brain imaging techniques and target markers within a given technique should mainly depend on the hypothesis regarding the mechanism of action of the intervention, level (structural, metabolic or functional) and anticipated timescale of the intervention's effects, target population, availability and costs of the techniques.

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Nutritional and environmental effects on reproduction in small ruminants

Reproduction Fertility and Development ◽

10.1071/rd04035 ◽

2004 ◽

Vol 16 (4) ◽

pp. 491 ◽

Cited By ~ 74

Author(s):

G. B. Martin ◽

J. Rodger ◽

D. Blache

Keyword(s):

Small Ruminants ◽

Cellular Biology ◽

Cellular Processes ◽

Physiological Processes ◽

Reproductive Axis ◽

Wide Range ◽

Short And Long Term ◽

The Impact ◽

The Brain

Animals live in environments that are both complex and continually changing, so they have to respond to short- and long-term variations in a wide range of factors, such as photoperiod, nutrition and sociosexual signals. Before they were domesticated, animals developed reproductive strategies that coped with these changes and often took advantage of them. The physiological processes that implement these strategies have been modified to some extent during several millennia of controlled breeding, but most persist. Thus, many genotypes still exhibit profound responses to external inputs, such as the induction of ovulation by sociosexual signals and the doubling of litter size by a change in nutrition. The complexity in these responses is now becoming clearer. For example, with sociosexual signals, we now need to consider the stimulatory effects of males on females, of females on males and of females on females. Similarly, the impact of nutrition has been extended beyond the control of puberty and the production of gametes to include phenomena such as ‘fetal programming’, with its potentially profound effects on the life-long performance of the animals. Fortunately, our capacity to research these phenomena has been greatly enhanced by technical improvements in hormone assays, molecular and cellular biology, and real-time ultrasound. This has brought us a better understanding of several of the environmental influences on reproduction, including: the cellular processes within ovarian follicles that mediate the effect of nutrition on ovulation rate; the neuroendocrine pathways through which nutritional inputs affect the brain centres that control appetite and reproduction; and the intracerebral pathways through which sociosexual signals (olfactory and non-olfactory) stimulate the reproductive axis. Importantly, we are now beginning to realise that, as well as considering interactions between environmental inputs and genotype, we need to take into account interactions between the environmental factors themselves, just as the animals do. We still have a long way to go for a complete understanding, but we are nevertheless in a position where we can begin to use this information to develop new management systems for our animals to improve their productivity.

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The Effects of Retesting on the Mechanical Properties of the Brain Tissue

ASME 2013 2nd Global Congress on NanoEngineering for Medicine and Biology ◽

10.1115/nemb2013-93101 ◽

2013 ◽

Author(s):

Asghar Rezaei ◽

Ghodrat Karami ◽

Fardad Azarmi ◽

Mehdi Salimi Jazi ◽

Mariusz Ziejewski

Keyword(s):

Mechanical Properties ◽

Brain Tissue ◽

Relaxation Times ◽

Stress Relaxation Test ◽

Preparation Time ◽

Relaxation Functions ◽

Before And After ◽

Short And Long Term ◽

The Brain

This research is intended to examine the amount of changes that can happen in material characteristics after retesting. Stress relaxation test is conducted on the same samples of the swine brain tissue for several times in small and large deformations. The mechanical properties of the substance are calculated before and after retest and the constants of the tissue, as mechanical characteristics, are determined and compared. Short- and long-term moduli, relaxation times and relaxation functions are of those data that are calculated and compared to understand how much they decay after repeating the experiments. The results show that applying different tests on one sample slightly changes the mechanical properties of the tissue and, as a result, it is partly possible to perform more than one test on the same sample resulting in less sample preparation, time and effort.

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Towards an integration of deep learning and neuroscience

10.1101/058545 ◽

2016 ◽

Cited By ~ 5

Author(s):

Adam Henry Marblestone ◽

Greg Wayne ◽

Konrad P Kording

Keyword(s):

Machine Learning ◽

Memory Storage ◽

Cost Functions ◽

Long Term Memory ◽

Recent Developments ◽

Short And Long Term ◽

The Brain ◽

And Training ◽

Learning Data

Neuroscience has focused on the detailed implementation of computation, studying neural codes, dynamics and circuits. In machine learning, however, artificial neural networks tend to eschew precisely designed codes, dynamics or circuits in favor of brute force optimization of a cost function, often using simple and relatively uniform initial architectures. Two recent developments have emerged within machine learning that create an opportunity to connect these seemingly divergent perspectives. First, structured architectures are used, including dedicated systems for attention, recursion and various forms of short- and long-term memory storage. Second, cost functions and training procedures have become more complex and are varied across layers and over time. Here we think about the brain in terms of these ideas. We hypothesize that (1) the brain optimizes cost functions, (2) these cost functions are diverse and differ across brain locations and over development, and (3) optimization operates within a pre-structured architecture matched to the computational problems posed by behavior. Such a heterogeneously optimized system, enabled by a series of interacting cost functions, serves to make learning data-efficient and precisely targeted to the needs of the organism. We suggest directions by which neuroscience could seek to refine and test these hypotheses.

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Application of Ultrasonography to Neuro-COVID-19

10.21203/rs.3.rs-776630/v1 ◽

2021 ◽

Author(s):

Marco Ruggiero

Keyword(s):

Immune Responses ◽

Psychiatric Symptoms ◽

Specific Adaptation ◽

Antiviral Therapies ◽

The Central Nervous System ◽

Diagnostic Ultrasonography ◽

Short And Long Term ◽

Psychiatric Manifestations ◽

The Brain

Abstract Neurological and psychiatric symptoms are frequently observed in COVID-19, the disease caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), and the term "Neuro-COVID-19" has been coined to indicate the plethora of short- and long-term neurologic and psychiatric manifestations. In a significant percentage of cases, neuro-psychiatric symptoms persist after recovery and long-term sequelae have been reported. SARS-CoV-2 can infect the brain through different routes and the damage can be direct, that is due to the virus itself, or indirect, that is associated with abnormal immune responses, inflammation, and hypoxia. Studies of brain specimens obtained from autopsy demonstrated the presence of the virus in a minority of cases and this leads to hypothesize that SARS-CoV-2 may hide in sanctuary sites in the central nervous system in analogy with what observed for HIV. The existence of sanctuary sites for SARS-CoV-2 has the potential to decrease the efficacy of antiviral therapies or vaccination and may even prevent complete eradication of SARS-CoV-2 from the infected organism. In 2017, a diagnostic and therapeutic procedure was proposed with the goal of identifying and treating pathogens hiding in sanctuaries that elude diagnosis and therapy. This procedure is based on clinical evaluation, diagnostic ultrasonography, therapeutic ultrasounds, and laboratory analyses. Here, it is demonstrated that application of ultrasonography to Neuro-COVID-19 requires a specific adaptation that takes into account brain movements synchronous with breathing as well as the sensitivity of SARS-CoV-2 to ultrasounds.

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CCR5 Activation Promotes NLRP1-Dependent Neuronal Pyroptosis via CCR5/PKA/CREB Pathway After Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.120.033285 ◽

2021 ◽

Author(s):

Jun Yan ◽

Weilin Xu ◽

Cameron Lenahan ◽

Lei Huang ◽

Jing Wen ◽

...

Keyword(s):

Protein Kinase ◽

Underlying Mechanism ◽

Camp Response Element Binding ◽

Neurological Deficits ◽

Camp Response Element ◽

Chemokine Ligand ◽

Short And Long Term ◽

The Brain ◽

Kinase A

Background and Purpose: Neuronal pyroptosis is a type of regulated cell death triggered by proinflammatory signals. CCR5 (C-C chemokine receptor 5)-mediated inflammation is involved in the pathology of various neurological diseases. This study investigated the impact of CCR5 activation on neuronal pyroptosis and the underlying mechanism involving cAMP-dependent PKA (protein kinase A)/CREB (cAMP response element binding)/NLRP1 (nucleotide-binding domain leucine-rich repeat pyrin domain containing 1) pathway after experimental intracerebral hemorrhage (ICH). Methods: A total of 194 adult male CD1 mice were used. ICH was induced by autologous whole blood injection. Maraviroc (MVC)—a selective antagonist of CCR5—was administered intranasally 1 hour after ICH. To elucidate the underlying mechanism, a specific CREB inhibitor, 666-15, was administered intracerebroventricularly before MVC administration in ICH mice. In a set of naive mice, rCCL5 (recombinant chemokine ligand 5) and selective PKA activator, 8-Bromo-cAMP, were administered intracerebroventricularly. Short- and long-term neurobehavioral assessments, Western blot, Fluoro-Jade C, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunofluorescence staining were performed. Results: The brain expression of CCL5 (chemokine ligand 5), CCR5, PKA-Cα (protein kinase A-Cα), p-CREB (phospho-cAMP response element binding), and NLRP1 was increased, peaking at 24 hours after ICH. CCR5 was expressed on neurons, microglia, and astrocytes. MVC improved the short- and long-term neurobehavioral deficits and decreased neuronal pyroptosis in ipsilateral brain tissues at 24 hours after ICH, which were accompanied by increased PKA-Cα and p-CREB expression, and decreased expression of NLRP1, ASC (apoptosis-associated speck-like protein containing a CARD), C-caspase-1, GSDMD (gasdermin D), and IL (interleukin)-1β/IL-18. Such effects of MVC were abolished by 666-15. At 24 hours after injection in naive mice, rCCL5 induced neurological deficits, decreased PKA-Cα and p-CREB expression in the brain, and upregulated NLRP1, ASC, C-caspase-1, N-GSDMD, and IL-1β/IL-18 expression. Those effects of rCCL5 were reversed by 8-Bromo-cAMP. Conclusions: CCR5 activation promoted neuronal pyroptosis and neurological deficits after ICH in mice, partially through the CCR5/PKA/CREB/NLRP1 signaling pathway. CCR5 inhibition with MVC may provide a promising therapeutic approach in managing patients with ICH.

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Is coding a relevant metaphor for building AI?

Behavioral and Brain Sciences ◽

10.1017/s0140525x19001365 ◽

2019 ◽

Vol 42 ◽

Cited By ~ 1

Author(s):

Adam Santoro ◽

Felix Hill ◽

David Barrett ◽

David Raposo ◽

Matt Botvinick ◽

...

Keyword(s):

Artificial Intelligence ◽

Neural Coding ◽

Changing Environment ◽

Short And Long Term ◽

The Brain

Abstract Brette contends that the neural coding metaphor is an invalid basis for theories of what the brain does. Here, we argue that it is an insufficient guide for building an artificial intelligence that learns to accomplish short- and long-term goals in a complex, changing environment.

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