1,721,164 research outputs found
Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: implications for ischemia and Huntington's disease
No full textStriatal spiny neurons are selectively vulnerable in Huntington's disease (HD) and ischemia, whereas large aspiny (LA) cholinergic interneurons of the striatum are spared in these pathological conditions. We have investigated whether a different sensitivity to ionotropic glutamatergic agonists might account for this differential vulnerability. Intracellular recordings were obtained from morphologically identified striatal spiny neurons and LA cholinergic interneurons by using a rat brain slice preparation. The two striatal neuronal subtypes had strikingly different intrinsic membrane properties. Both subtypes responded to cortical stimulation with excitatory postsynaptic potentials: these potentials, however, had a different time course and pharmacology in the two classes of cells. Interestingly, membrane depolarizations and inward currents produced by exogenous glutamate receptor agonists (AMPA, kainate, and NMDA) were remarkably larger in spiny neurons than in LA interneurons. Moreover, concentrations of agonists producing reversible membrane changes in LA interneurons caused irreversible depolarizations in spiny cells. Our data suggest that the different physiological responses induced by the activation of ionotropic glutamate receptors may account for the cell type-specific vulnerability of striatal neurons in ischemia and HD
Neuropathic pain impact on sleep and circadian rhythm of blood pressure in painful diabetic polyneuropathy
No full textA Novel Association Between Nondipping and Painful Diabetic Polyneuropathy
No full textWe hypothesized the meaningful coexistence of neuropathic pain and nondipping in painful diabetic polyneuropathy (PDPN).RESEARCH DESIGN AND METHODS: In 113 patients with PDPN, with painless diabetic polyneuropathy (DPN(+)) and without DPN (DPN(-)), neuropathic pain, sleep, risk for obstructive sleep apnea (OSA), autonomic function, and blood pressure (BP) circadian pattern were assessed using the Douleur Neuropathique en 4 Questions (DN4), the Medical Outcomes Study Sleep Scale, the Berlin Questionnaire, cardiovascular reflex tests, and ambulatory BP monitoring.RESULTS: Patients with PDPN showed higher nighttime systolic BP (130.4 ± 15.6 mmHg) than both DPN(-) (119.9 ± 10.6 mmHg; P < 0.0001) and DPN(+) patients (124.2 ± 12.3 mmHg; P < 0.05), and lower day-night difference (∆) in systolic BP (5.5 ± 6.5 vs. 8.6 ± 7.7%; P < 0.05) and diastolic BP than DPN(-) patients. In a stepwise regression analysis, orthostatic hypotension, high risk for OSA, and PDPN (DN4 interview) were independent determinants of ∆ in systolic BP (r = 0.46; P = 0.0001), ∆ in diastolic BP, and nighttime systolic BP.CONCLUSIONS: PDPN is associated with higher nocturnal systolic BP and impaired BP circadian pattern independent of pain-related comorbidities, suggesting a condition of high cardiovascular risk
Optimizing the "Time to pregnancy" in women with multiple sclerosis: the OPTIMUS Delphi survey
No full textbackground :the debate on how to manage women affected by multiple sclerosis (MS) during reproductive age is still open, as is the issue of fertility in such patients. main issue regard the identification of the optimal window for pregnancy and how to deal with medical therapy before and during conception. the aim of this delphi consensus was to collect the opinions of a multidisciplinary group, involving reproductive medicine specialists and neurologists with experience in the management of multiple sclerosis women with reproductive desire.Methods :Four experts plus scientific coordinators developed a questionnaire distributed online to 10 neurologists and later discussed the responses and amended a list of statements. the statements were then distributed via an online survey to 23 neurologists (comprising the first 10), who voted on their level of agreement/disagreement with each statement. consensus was achieved if agreement or disagreement with a statement exceeded 66%.results: twenty-one statements reached consensus after two rounds of voting, leading to the following main recommendations: (1) fertility evaluation should be suggested to wMS, in case of the need to shorten time to pregnancy and before treatment switch in women on DMTs contraindicated in pregnancy, particularly in case of highly active disease and age > 35 years. (2) ART should not be discouraged in wMS, but the use of DMTs until pregnancy confirmation should be suggested; ART may be considered in order to reduce time to pregnancy in MS women with a reduced ovarian reserve and/or age > 35 years, but in case of an expected poor ART prognosis and the need for more than one ART cycle, a switch to a high-efficacy DMD before ART should be offered. (3) oocyte cryopreservation may be considered in women with reduced ovarian reserve, with unpredictable time to complete diagnostic workup and achieve disease control; a risk/cost-benefit analysis must be performed in women >35 years, considering the diminished ovarian reserve.conclusion :this consensus will help MS neurologists to support family planning in wMS, respecting MS therapeutic needs while also taking into account the safety and impact of advancing age on fertility
Studio della disabilità a lungo termine nella Sclerosi Multipla per mezzo della Stimolazione Magnetica Transcranica
No full textSynaptic transmission in the striatum: from plasticity to neurodegeneration
No full textStriatal neurones receive myriad of synaptic inputs originating from different sources. Massive afferents from all areas of the cortex and the thalamus represent the most important source of excitatory amino acids, whereas the nigrostriatal pathway and intrinsic circuits provide the striatum with dopamine, acetylcholine, GABA, nitric oxide and adenosine. All these neurotransmitter systems interact each other and with voltage-dependent conductances to regulate the efficacy of the synaptic transmission within this nucleus. The integrative action exerted by striatal projection neurones on this converging information dictates the final output of the striatum to the other basal ganglia structures. Recent morphological, immunohistochemical and electrophysiological findings demonstrated that the striatum also contains different interneurones, whose role in physiological and pathological conditions represents an intriguing challenge in these years. The use of the in vitro brain slice preparation has allowed not only the detailed investigation of the direct pre- and postsynaptic electrophysiological actions of several neurotransmitters in striatal neurones, but also the understanding of their role in two different forms of corticostriatal synaptic plasticity, long-term depression and long-term potentiation. These long-lasting changes in the efficacy of excitatory transmission have been proposed to represent the cellular basis of some forms of motor learning and are altered in animal models of human basal ganglia disorders, such as Parkinson's disease. The striatum also expresses high sensitivity to hypoxic-aglycemic insults. During these pathological conditions, striatal synaptic transmission is altered depending on presynaptic inhibition of transmitter release and opposite membrane potential changes occur in projection neurones and in cholinergic interneurones. These ionic mechanisms might partially explain the selective neuronal vulnerability observed in the striatum during global ischemia and Huntington's disease
Diabetic peripheral neuropathic pain is a stronger predictor of depression than other diabetic complications and comorbidities.
Full text linkAims: To investigate the independent effect on depression of painless diabetic polyneuropathy, painful diabetic polyneuropathy, and general and diabetes-related comorbidities.
Methods: In 181 patients, the presence of painless diabetic polyneuropathy, painful diabetic polyneuropathy, comorbidities and depression was assessed using the Michigan Neuropathy Screening Instrument Questionnaire, the Michigan Diabetic Neuropathy Score, nerve conduction studies, the Douleur Neuropathique en 4 Questions, the Charlson Comorbidity Index and the Beck Depression Inventory-II.
Results: In all, 46 patients met the criteria of confirmed painless diabetic polyneuropathy and 25 of painful diabetic polyneuropathy. Beck Depression Inventory-II scores indicative of mild-moderate-severe depression were reached in 36 patients (19.7%). In a multiple logistic regression analysis (including age, sex, body mass index, being unemployed, duration, haemoglobin A1c, insulin treatment, systolic blood pressure, nephropathy, retinopathy, Charlson Comorbidity Index and painful diabetic polyneuropathy), female sex (odds ratio: 5.9, p = 0.005) and painful diabetic polyneuropathy (odds ratio: 4.6, p = 0.038) were the only independent predictors of depression. Multiple regression analysis, including Douleur Neuropathique en 4 Questions and Michigan Diabetic Neuropathy Score instead of painful diabetic polyneuropathy, showed that Douleur Neuropathique en 4 Questions, in addition to female sex, was a significant predictor of depressive symptoms severity (p =0.005).
Conclusion: Painful diabetic polyneuropathy is a greater determinant of depression than other diabetes-related complications and comorbidities. Painful symptoms enhance depression severity more than objective insensitivity
Hereditary spastic paraplegia: a novel mutation and expansion of the phenotype variability in SPG10
No full textCommon polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes.
No full textAbstract Diabetic polyneuropathy (DPN) and cardiovascular
autonomic neuropathy (CAN) are common type 2
diabetes complications with a large inter-individual variability
in terms of clinical manifestations and severity. Our
aim was to evaluate a possible involvement of genetic
polymorphisms in miRNA regions in the susceptibility to
DPN and CAN. Nine polymorphisms in miRNA genes
were studied in a sample of 132 type 2 diabetes patients
(T2D) analysed for DPN and 128 T2D patients analysed for
CAN. A genotype–phenotype correlation analysis was
performed. The T allele of rs11888095 single nucleotide
polymorphism (SNP) in MIR128a was significantly associated
with a higher risk (ORadj = 4.89, Padj = 0.02),
whereas the C allele of rs2910164 SNP in MIR146a
was associated with a lower risk to develop DPN
(ORadj = 0.49, Padj = 0.09), respectively. A multivariate
logistic regression analysis confirmed that both SNPs
contribute to DPN (p\0.001 and p = 0.01 for MIR128a
and MIR146a, respectively). MIR128a SNP significantly
contributed also to DPN score (p = 0.026). Rs895819 SNP
in MIR27a was significantly associated with a higher risk
to develop early CAN (Padj = 0.023 and ORadj = 3.43).
The rs2910164 SNP in MIR146a showed a protective
effect respect to early CAN (Padj = 0.052, ORadj = 0.32)
and to confirmed CAN (Padj = 0.041, ORadj = 0.13). The
same SNP resulted significantly associated with a lower
CAN score and a higher E/I (p = 0.002 and p = 0.003,
respectively). In conclusion, we described associations of
MIR128a and MIR146a SNPs with DPN susceptibility and
of MIR146a and MIR27a SNPs with CAN susceptibility.
This is the first study showing that genetic variability in
miRNA genes could be involved in diabetic neuropathies
susceptibility
Validity of DN4 as a screening tool for neuropathic pain of painful diabetic polyneuropathy
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