49 research outputs found
The brain mechanisms underlying walking in complex situations in healthy older adults and persons with Parkinson's disease
No full textIntroduction: The ability to walk safely and independently is a fundamental component of daily living activities. Walking while dual tasking and obstacle negotiation are two tasks that have been used to investigate walking in complex situations. Deficits in cognitive domains and sensory-motor processes associated with aging and neurodegenration impair the ability to successfully assess the environment and react to it. These changes in the ability to walk are modulated via neural circuits. However, the actual neural circuits of the brain involved in the control of locomotion in different challenging situations are still poorly understood. Methods: Two groups of subjects; 20 healthy older adults (mean age 69.7±1.3 yrs, 50% females) and 47 persons with PD (mean age 71.7±1.1 yrs, 32% females) were studied. The protocol included real and imagined walking while negotiating obstacles and dual tasking. Walking conditions were performed while being monitored with fNIRS and imagined walking were assessed in the MR scanner. A repeated measures design (condition x group) was conducted with two levels; within group and between groups. Results: Significant differences in brain activation were observed in the fMRI and fNIRS. Between groups comparison showed that persons with PD had a significantly higher activation in frontal, parietal, occipital, and cerebellum regions during usual walking compared to healthy older adults (p<0.048). Comparison between the walking tasks within each group revealed (1) increased activation during walking while negotiating obstacles in both groups (p<0.023) and (2) increased activation during walking while dual tasking only in healthy older adults (p<0.035). Correlations between brain activation and performance in motor-cognitive tests were found in both groups however, healthy older adults presented inverse correlation and persons with PD positive correlation. Conclusions: These findings indicate that subjects with PD activate larger brain areas than healthy older adults even during usual walking. Perhaps, this increased activation is a compensatory strategy to enhance performance. The increased activation already during usual walking task may limit the ability to increase activation or recruit additional brain areas during the more complex walking tasks and may contribute to the high prevalence of falls and the dual tasking difficulty in persons with PD.Ph.D.Includes bibliographical referencesby Inbal Maida
The impact of glucocorticoids on bone health and growth: endocrine and non-endocrine effects in children and young patients
No full text: Glucocorticoids have numerous applications in short and/or long-term therapy both in pediatric and young adults, based on their significant anti-inflammatory and immunosuppressive effects. Different routes of administration can be provided including topical, inhalatory and oral. Topical treatments are the first choice for many dermatologic conditions. The inhalatory form is widely used in asthma management while systemic pathologies often require oral administration. The risks for adverse effects are related to the dose and duration of therapy as well as the specific agent used. Therefore, long-term treatment has a negative impact on different metabolic systems and can lead to hypertension, dyslipidemia and insulin resistance. In particular, many studies emphasize the direct and indirect effects of glucocorticoids on bone health. Glucocorticoids are the most common iatrogenic cause of osteoporosis and can alter bone development in young adults. These side effects are due to an early and transient increase in bone resorption and a decrease in bone formation. Glucocorticoid-induced changes can act on the bone multicellular unit, bone cells and intracellular signaling pathways. Chronic use can also modify bone mass though indirect endocrine and non-endocrine effects by reducing the anabolic function of sex steroids and GH/IGF-1 axis, interfere with calcium metabolism, as well as muscle atrophy and central fat accumulation. The aim of our review is to revise the available evidence on the impact of glucocorticoid treatment on bone health related to endocrine and non-endocrine effects in young patients
MRS of Brain Metabolite Levels Demonstrates the Ability of Scavenging of Excess Brain Glutamate to Protect against Nerve Agent Induced Seizures
No full textThis study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent
Diffusion MRI and Q-Space Diffusion MRI: From Cerebral Ischemia to Multiple Sclerosis and Beyond
No full textStructural changes in glutamate cell swelling followed by multiparametric q-space diffusion MR of excised rat spinal cord
No full textDiffusion in the extracellular and intracellular spaces (ECS and ICS, respectively) was evaluated in excised spinal cords, before and after cell swelling induced by glutamate, by high b-value q-space diffusion MR of specific markers and water. The signal decays of deuterated tetramethylammonium (TMA-d12) chloride, an exogenous marker of the ECS, and N-acetyl aspartate (NAA), an endogenous marker of the ICS, were found to be non-mono-exponential at all diffusion times. The signal decays of these markers were found to depend on the diffusion time and the cell swelling induced by the glutamate. It was found, for example, that the mean displacements of the apparent fast and slow diffusion components of TMA-d12 are 7.21 ± 0.11 and 1.16 ± 0.05 μm, respectively at a diffusion time of 496 ms. After exposure of the spinal cords to 10 mM of glutamate, these values decreased to 6.62 ± 0.13 and 1.01 ± 0.05 μm, respectively. The mean displacement of NAA, however, showed a less pronounced opposite trend and increased after cell swelling induced by exposure to glutamate. q-Space diffusion MR of water was found to be sensitive to exposure to glutamate, and q-space diffusion MRI showed that a more pronounced decrease in the apparent diffusion coefficient and the mean displacement of water is observed in the gray matter (GM) of the spinal cord. All these changes demonstrate that diffusion MR is indeed sensitive to structural changes caused by cell swelling induced by glutamate. Multiparametric high b-value q-space diffusion MR is useful for obtaining microstructural information in neuronal tissues
Cerebellar learning properties are modulated by the CRF receptor in granular cells
Get PDFCorticotropin-releasing factor (CRF) and its type 1 receptor (CRFR1) play an important role in the responses to stressful challenges. Despite the well-established expression of CRFR1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive. To investigate the role of CRFR1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR1 in these cells. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity. Moreover, male mice depleted of CRFR1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion or fear and anxiety-related behaviors. Last, we analyzed cerebella transcriptome of KO and control mice and detected prominent alterations in the expression of calcium signaling pathways components. Our findings shed light on the interplay between stress-related central mechanisms and cerebellar motor conditioning, highlighting the role of the CRF system in regulating particular forms of cerebellar learning.SIGNIFICANCE STATEMENTAlthough it is known that CRFR1 is highly expressed in the cerebellum, little attention has been given to its role in cerebellar functions in the behaving animal. Moreover, most of the attention was directed to the effect of CRF on Purkinje cells at the cellular level, and to this date, almost no data exist on the role of this stress-related receptor in other cerebellar structures. Here, we explored the behavioral and cellular effect of GrCs specific ablation of CRFR1 We found a profound effect on learning, both at the cellular and behavioral levels, without affecting baseline motor skills
Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer
No full textNitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation. We find that induction of endogenous NO production by enterocytes with supplements that upregulate ASL expression and complement its substrates results in improved epithelial integrity and alleviation of colitis and of inflammation-associated colon cance
Bimodal magnetic resonance and optical imaging of extracellular matrix remodelling by orthotopic ovarian tumours
No full textISSN:0007-0920ISSN:1532-1827ISSN:1532-182
