In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease.

We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain.

Tissue degeneration in ALS affected spinal cord evaluated by Raman spectroscopy.

The Raman spectral features from spinal cord tissue sections of transgenic, ALS model mice and non-transgenic mice were compared using 457 nm excitation line, profiting from the favourable signal intensity obtained in the molecular fingerprint region at this wavelength. Transverse sections from four SOD1G93A mice at 75 days and from two at 90 days after birth were analysed and compared with sections of similarly aged control mice. The spectra acquired within the grey matter of tissue sections from the diseased mice is markedly different from the grey matter signature of healthy mice.

From Traumatic Childhood to Cocaine Abuse: The Critical Function of the Immune System.

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder, but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system, and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of substance use disorder in individuals who have experienced early life stress is unknown.

Proteomics and Toxicity Analysis of Spinal-Cord Primary Cultures upon Hydrogen Sulfide Treatment.

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter recognized as an essential body product with a dual, biphasic action. It can function as an antioxidant and a cytoprotective, but also as a poison with a high probability of causing brain damage when present at noxious levels. In a previous study, we measured toxic liquoral levels of H₂S in sporadic amyotrophic lateral sclerosis (ALS) patients and in the familial ALS (fALS) mouse model, SOD1G93A.

Lacosamide may improve cognition in patients with focal epilepsy: EpiTrack to compare cognitive side effects of lacosamide and carbamazepine.

Carbamazepine (CBZ) is a first generation anti-seizure drug, considered as first choice therapy in focal epilepsy but associated with cognitive side effects. Lacosamide (LCM) is a third-generation anti-seizure drug approved for treating focal epilepsy. This case series documented the comparable efficacy of LCM and CBZ as first add on treatments in patients affected by uncontrolled focal seizures.

Clinical value of CSF amyloid-beta-42 and tau proteins in Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is a four-repeat tauopathy with high phenotypic and neuropathological variability, highlighting the urgent need for effective disease biomarkers. Quantitative analysis of cerebrospinal fluid (CSF) proteins reflecting pathological changes of CNS is currently used as biomarkers of multiple neurodegenerative disorders for both early differential diagnosis and prognostic clustering of patients. In this study, we thus assessed the clinical usefulness of a panel of CSF biomarker in PSP patients presenting with Richardson's Syndrome.

Reversal of dopamine-mediated firing inhibition through activation of the dopamine transporter in substantia nigra pars compacta neurons.

Background And Purpose: One of the hallmarks of ventral midbrain dopamine-releasing neurons is membrane hyperpolarization in response to stimulation of somato-dendritic D receptors. At early postnatal age, under sustained dopamine, this inhibitory response is followed by a slow recovery, resulting in dopamine inhibition reversal (DIR). In the present investigation, we aimed to get a better insight into the cellular mechanisms underlying DIR.

Amyloid-Mediated Cholinergic Dysfunction in Motor Impairment Related to Alzheimer's Disease.

Background: Although motor disturbances parallel the course of dementia, worsening both quality of life and social costs, the pathogenesis remains still unclear.

Objective: Through the combination of cerebrospinal fluid (CSF) biomarkers assessment and transcranial magnetic stimulation (TMS) protocols, here we provided a cross-sectional study to understand pathogenic mechanisms of Alzheimer's disease (AD)-related early motor disturbances.

Methods: The motor phenotype, as defined with Unified Parkinson's Disease Rating Scale (UPDRS) part 2-3, Rating Scale for Gait Evaluation in Cognitive Deterioration (RSEGCD) and Tinetti scale, together with CSF profile of amyloid-β 42 (Aβ42), total-tau, and phosphorylated-tau were determined in 37 AD patients and compared to 18 patients with vascular dementia (VaD).

Continuous Positive Airway Pressure Treatment May Improve Optic Nerve Function in Obstructive Sleep Apnea: An Electrophysiological Study.

Study Objectives: Obstructive sleep apnea (OSA) is a sleep disorder frequently associated with optic nerve diseases. Moreover, untreated patients with severe OSA may show optic nerve dysfunction as documented by electrophysiological studies using visual evoked potentials (VEP). Because continuous positive airway pressure (CPAP) treatment has proved to restore the physiologic nocturnal breathing, thus preventing nocturnal hypoxemia and reducing inflammation, in this study we tested whether 1-year CPAP treatment may modify VEP responses in patients with severe OSA.

Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease.

The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD.

Dystonia as a network disorder: a concept in evolution.

Purpose Of Review: This survey takes into consideration the most recent advances in both human degenerative ataxias, disorders with a well established cerebellar origin, and discoveries from dystonia rodent models aimed at discussing the pathogenesis of dystonia.

Recent Findings: One common recurrent term that emerges when describing dystonia is heterogeneity. Indeed, dystonia encompasses a wide group of 'hyperkinetic' movement disorders, with heterogeneous causes, classification, anatomical and physiological substrates.

Does Pisa syndrome affect upper limb function in patients with Parkinson's disease? An observational cross-sectional study.

Background: Trunk alignment is thought to contribute to upper limb (UL) function. However, this common assumption is not clear in patients with Parkinson's Disease (PD) suffering from Pisa syndrome (PS). PS is a postural abnormality, characterized by revisable lateral trunk flexion more than 10 degrees.

Centrality of Early Synaptopathy in Parkinson's Disease.

Significant advances have been made in the understanding of the numerous mechanisms involved in Parkinson's disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses.

When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression.

Late-life depression (LLD) and Alzheimer's Disease (AD) are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging.

3,4-Methylenedioxymethamphetamine (MDMA) Alters Synaptic Dopamine Release in the Dorsal Striatum Through Nicotinic Receptors and DAT Inhibition.

An increase of extracellular dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine (MDMA). Although this drug has been reported to affect the DA uptake transporter (DAT), it might activate other mechanisms to regulate the outflow of DA in the brain. Our aim was to examine the overall effects of MDMA on the release of DA in the striatum.

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum.

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded.

Ambra1 Shapes Hippocampal Inhibition/Excitation Balance: Role in Neurodevelopmental Disorders.

Imbalances between excitatory and inhibitory synaptic transmission cause brain network dysfunction and are central to the pathogenesis of neurodevelopmental disorders. Parvalbumin interneurons are highly implicated in this imbalance. Here, we probed the social behavior and hippocampal function of mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene crucial for brain development.

Does continuous positive airway pressure treatment affect autonomic nervous system in patients with severe obstructive sleep apnea?

Objective: This study is aimed at evaluating whether Continuous Positive Airway Pressure treatment (CPAP) may affect autonomic nervous system (ANS) in male patients with severe obstructive sleep apnea (OSAS).

Methods: We compared autonomic symptoms of de novo severe OSAS patients, OSAS patients on chronic CPAP treatment and healthy controls, using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire. All groups underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip and cold face tests.

Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory.

The neurotrophic factors neuregulins (NRGs) and their receptors, ErbB tyrosine kinases, regulate neurotransmission, synaptic plasticity and cognitive functions and their alterations have been associated to different neuropsychiatric disorders. Group 1 metabotropic glutamate receptors (mGluRI)-dependent mechanisms are also altered in animal models of neuropsychiatric diseases, especially mGluRI-induced glutamatergic long-term depression (mGluRI-LTD), a form of synaptic plasticity critically involved in learning and memory. Despite this evidence, a potential link between NRGs/ErbB signalling and mGluRI-LTD has never been considered.

Efficacy and tolerability of perampanel and levetiracetam as first add-on therapy in patients with epilepsy: A retrospective single center study.

Perampanel (PER) is a third generation antiepileptic drug (AED), recently approved as add-on therapy in both focal and generalized seizures. Levetiracetam (LEV) is a second generation AED, widely used in patients with epilepsy because of its favorable safety and efficacy profiles. Perampanel and LEV treatments have been associated with the occurrence of similar adverse events (AEs) (sleepiness, irritability, depression, anxiety, aggressiveness).

The role of dopaminergic midbrain in Alzheimer's disease: Translating basic science into clinical practice.

Mammalian brain cortical functions, from executive and motor functioning to memory and emotional regulation, are strictly regulated by subcortical projections. These projections terminate in cortical areas that are continuously influenced by released neurotransmitters and neuromodulators. Among the subcortical structures, the dopaminergic midbrain plays a pivotal role in tuning cortical functions that commonly result altered in many neurological and psychiatric disorders.