Neuroscience
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In Parkinson's disease (PD) levodopa-associated changes in the power and long-range temporal correlations of beta oscillations have been demonstrated, yet the presence and modulation of genuine connectivity in local field potentials (LFP) recorded from the subthalamic nucleus (STN) remains an open question. The present study investigated LFP recorded bilaterally from the STN at wakeful rest in ten patients with PD after overnight withdrawal of levodopa (OFF) and after a single dose levodopa administration (ON). We utilized connectivity measures being insensitive to volume conduction (functional connectivity: non-zero imaginary part of coherency; effective connectivity: phase-slope index). ⋯ The OFF-ON differences in functional connectivity were correlated with the levodopa-induced improvement in clinical Unified Parkinson's Disease Rating Scale scores. We hypothesize that regional neuronal interactions, as reflected in STN-LFP connectivity, might represent a basis for the intra-nuclear spatial specificity of deep brain stimulation. Moreover, our results suggest the potential use of volume conduction-insensitive measures of connectivity in STN-LFP as a marker of clinical motor symptoms in PD.
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Hydrogen sulfide (H2S) is a gasotransmitter endogenously generated from the metabolism of L-cysteine by action of two main enzymes called cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). This gas has been involved in the pain processing and insulin resistance produced during diabetes development. However, there is no evidence about its participation in the peripheral neuropathy induced by this metabolic disorder. ⋯ Paradoxically, H2S levels were decreased in nerve sciatic, dorsal root ganglion and spinal cord, but not paw nor blood plasma, during diabetes-associated peripheral neuropathy development. Collectively, results suggest that H2S synthesized by CBS and CSE participate in formalin-induced nociception in diabetic and non-diabetic rats, as well as; in tactile allodynia in streptozotocin-injected rats. In addition, data seems to indicate that diabetic rats are more sensible to H2S-induced hyperalgesia than normoglycemic rats.
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Abnormal plasticity in the cortico-basal ganglia-thalamocortical loop has been suggested to represent a key factor in the pathophysiology of dystonia. In a model of primary paroxysmal dystonia, the dt(sz) mutant hamster, previous experiments have shown a strongly increased long-term potentiation (LTP) in comparison to non-dystonic control hamsters. These basal changes, i.e. in the absence of dystonia, were found in young animals at an age of 5 weeks, when the age-dependent dystonia in dt(sz) mutant reaches highest severity. ⋯ The present data show that in slices of young mutant hamsters the extent of LTP was not influenced by the presence of dystonia: In comparison to age-matched control hamsters, LTP was increased in mutant hamsters independent of preceding stressful stimulation. After remission of dystonia, i.e., in older dt(sz) mutant hamsters >10 weeks, only LTP could be elicited, while in preparations from age-matched control hamsters, either LTP or long-term depression developed, depending on previous behavioral challenge. We conclude that in mature brain, corticostriatal connections have the potential for changes in metaplasticity, while in dt(sz) mutant hamsters this metaplasticity is persistently infringed even though stress-inducible dystonic symptoms are lost.
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Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. ⋯ When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism.
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Compression of spinal roots is an important medical problem, which may arise from intervertebral disc herniation, tumor growth or as a result of high energy accidents. Differently from avulsion, root crushing maintains the central/peripheral nervous system (CNS/PNS) connection, although the axons are axotomized and motoneurons degenerate. Such neuronal death may decrease and delay motor function recovery. ⋯ Such treatment also improves the number of synapses immunoreactive against molecules present in inhibitory inputs. Also, an increased number of regenerated axons was obtained in the MSC-treated group, in comparison to the DMEM-treated control. Overall, MSC therapy acutely improved limb strength and gait coordination, indicating a possible clinical application of such treatment following proximal lesions at the CNS/PNS interface.