Restless legs syndrome (RLS) is a common sensory-motor circadian disorder, whose basic components include urge to move the legs, unpleasant sensory experience, and periodic leg movements during ...sleep, all associated with an enhancement of the individual's arousal state. Brain iron deficiency (BID) is considered to be a key initial pathobiological factor, based on alterations of iron acquisition by the brain, also moderated by genetic factors. In addition to the well-known dopaminergic involvement in RLS, previous studies pointed out that BID brings also a hyperglutamatergic state that influences a dysfunctional cortico-striatal-thalamic-cortical circuit in genetically vulnerable individuals. However, the enhancement of arousal mechanisms in RLS may also be explained by functional changes of the ascending arousal systems and by deficitary GABA-mediated inhibitory control. Very recently, it was also suggested that BID induces a hypoadenosinergic state in RLS, thus possibly providing a link for a putative unified pathophysiological mechanism accounting for both hyperarousal and sensory-motor signs. Consequently, RLS might be viewed as a multitransmitter neurochemical disorder, globally resulting in enhanced excitability and decreased inhibition. In this framework, understanding the complex interaction of different neuronal circuits in generating the symptoms of RLS is mandatory both for a better diagnostic refinement and for an innovative therapeutic support. Notably, multiple neurotransmission dysfunction, either primary or triggered by BID, may also bridge the gap between RLS and other chronic pain disorders. This chapter summarizes the current experimental and clinical findings into a heuristic model of the electrophysiology and neurochemistry underlying RLS.
Cognitive impairment, also known as cognitive decline, can occur gradually or suddenly and can be temporary or more permanent. It represents an increasingly important public health problem and can ...depend on normal aging or be linked to different neurodegenerative disorders, including Alzheimer's disease (AD). It is now well-established that lifestyle factors including dietary patterns play an important role in healthy aging as well as in the prevention of cognitive decline in later life. Among the natural compounds, dietary polyphenols including phenolic acids have been recently the focus of major attention, with their supplementation being associated with better cognitive status and prevention of cognitive decline. Despite their therapeutic potential, human studies investigating the relation between phenolic acids intake and cognitive outcomes are rather scarce. In this review, we provide preclinical evidence that different dietary polyphenols such as rosmarinic acid, ellagic acid, and cinnamic aldehyde can exert neuroprotective and pro-cognitive activities through different molecular mechanisms including the modulation of pro-oxidant and antioxidant machinery as well as inflammatory status. Future and more numerous in vivo studies are needed to strengthen the promising results obtained at the preclinical level. Despite the excellent pharmacokinetic properties of phenolic acids, which are able to be accumulated in the brain at pharmacologically relevant levels, future studies should also identify which among the different metabolites produced as a consequence of phenolic acids' consumption may be responsible for the potential neuroprotective effects of this subgroup of polyphenols.
Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological ...manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called "cytokine storm"), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.
Acute brain ischemia causes changes in several neural networks and related cortico-subcortical excitability, both in the affected area and in the apparently spared contralateral hemisphere. The ...modulation of these processes through modern techniques of noninvasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), has been proposed as a viable intervention that could promote post-stroke clinical recovery and functional independence. This review provides a comprehensive summary of the current evidence from the literature on the efficacy of rTMS applied to different clinical and rehabilitative aspects of stroke patients. A total of 32 meta-analyses published until July 2019 were selected, focusing on the effects on motor function, manual dexterity, walking and balance, spasticity, dysphagia, aphasia, unilateral neglect, depression, and cognitive function after a stroke. Only conventional rTMS protocols were considered in this review, and meta-analyses focusing on theta burst stimulation only were excluded. Overall, both HF-rTMS and LF-rTMS have been shown to be safe and well-tolerated. In addition, the current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and cognitive impairment, where definitive evidence of efficacy cannot be drawn. However, routine use of a specific paradigm of stimulation cannot be recommended yet due to a significant level of heterogeneity of the studies in terms of protocols to be set and outcome measures that have to be used. Future studies need to preliminarily evaluate the most promising protocols before going on to multicenter studies with large cohorts of patients in order to achieve a definitive translation into daily clinical practice.
In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an "umbrella term" encompassing any degree of ...vascular-related cognitive decline, VCI is deemed to be the most common cognitive disorder in the elderly, with a significant impact on social and healthcare expenses. Interestingly, some of the molecular, biochemical, and electrophysiological abnormalities detected in VCI seem to correlate with disease process and progression, eventually promoting an adaptive plasticity in some patients and a maladaptive, dysfunctional response in others. However, the exact relationships between vascular lesion, cognition, and neuroplasticity are not completely understood. Recent findings point out also the possibility to identify a panel of markers able to predict cognitive deterioration in the so-called "brain at risk" for vascular or mixed dementia. This will be of pivotal importance when designing trials of disease-modifying drugs or non-pharmacological approaches, including non-invasive neuromodulatory techniques. Taken together, these advances could make VCI a potentially preventable cause of both vascular and degenerative dementia in late life. This review provides a timely update on the recent serological, cerebrospinal fluid, histopathological, imaging, and neurophysiological studies on this "cutting-edge" topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients.
DFT-M062X quantum chemical computations on the Ala3H(+)·nH2O (n up to 37) complexes have been performed to model for hydration effects on the molecular properties of protonated trialanine. Following ...simple rules to arrange water molecules around the peptide, geometry optimization allows us to find four minima corresponding to the unfolded extended (β) and polyproline II (PPII) conformations. The peptide is incorporated into the network of hydrogen bonds of interfacial water molecules with a hydration energy of about -85 kcal mol(-1). The progressive hydration of the peptide shows a more efficient intermolecular hydrogen bonding in the PPII arrangement, and the following relative electronic energy stability β-β < β-PPII ≈ PPII-β < PPII-PPII has been found. The conformational entropy term proceeds in the reverse direction, thus these changes compensate in a way that leads to small changes in Gibbs free energy. These findings agree with experimental data which report an equilibrium between these conformers modulated by temperature.
Healthy successful aging with preserved mental and cognitive health is expected to be one of the most important challenges of the growing old population globally. Studies investigating these ...multi-dimensional aspects of senescence are important to identify potential targets for early prevention. The aim of this study was to investigate the relation between adherence to the Mediterranean diet and mental and cognitive health, quality of life, and successful aging in middle-age and older adults living in Sicily, southern Italy. Data from a sample of 883 individuals was collected including information on food intake (through a 110-item food frequency questionnaire), sleep quality (through the Pittsburgh sleep quality index) depressive symptoms (through the Center for the Epidemiological Studies of Depression Short Form), quality of life (through the Manchester Short Assessment of Quality of Life), cognitive status (through the Short Portable Mental Status Questionnaire), and overall successful aging (through the Successful Aging Index). Multivariate logistic regression analyses were conducted to assess the association between adherence to the Mediterranean diet and the outcomes investigated. After adjustment for potential confounding factors, individuals in the highest quartile of adherence to the Mediterranean diet were less likely to have cognitive impairment (OR = 0.19, 95 % CI: 0.04, 0.86), depressive symptoms (OR = 0.19, 95 % CI: 0.08, 0.46) and more likely to have good quality of life (OR = 14.04, 95 % CI: 6.81, 28.93); significant results were also found for individuals in the third quartile of Mediterranean diet adherence and good sleep quality (OR = 1.65, 95 % CI: 1.03, 2.64). Moreover, individuals in the highest quartile of adherence were more likely to have a successful aging (OR = 1.65, 95 % CI: 1.01, 2.68). In conclusion, this study supports the hypothesis that adherence to the Mediterranean diet provides a positive trajectory toward a healthy successful aging, with major potential benefits toward mental and cognitive health.
•Successful aging is a multi-dimensional concept describing physical and mental well-being in older adults.•Higher adherence to the Mediterranean diet was associated with better mental and cognitive health.•Individuals more adherent to the Mediterranean diet were more likely to have a successful aging.
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