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Biomedicines
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State-of-the-Art Neurologic Disease in Italy
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State-of-the-Art Neurologic Disease in Italy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 19979

Special Issue Editor

Dr. Carmela Matrone

E-Mail Website
Guest Editor
Department of Neurosciences, School of Medicine, University of Naples “Federico II”, Via Sergio Pansini 5, 80131 Naples, Italy
Interests: genetics; chemistry pharmacology; toxicology; Alzheimer; neurodegenerative disease; parkinson’s disease; dementia; stem cells; amyloid; regenerative medicine; dopamine

Special Issue Information

Dear Colleagues,

The aim of this Special Issue is to provide a state-of-the-art review on the current knowledge and management of psychiatric and neurologic diseases in Italy, including aspects related to the molecular effects of COVID‐19 pandemic on brain functions in Italy.

The purpose is to share evidence concerning the most recent development and perspectives in research and clinical management of patients with brain disorders, such as stroke and other neurologic conditions involving the central nervous system and peripheral nerves, as well as psychiatric disorders and neurodegenerative diseases.

Neurologists, neuropsychiatrists, psychologists and basic research scientists are encouraged to submit studies concerning new potential biomarkers targetable for innovative therapeutic strategies and innovative evidence reporting new mechanisms or novel genetic as well as metabolic risk factors in psychiatric and neurologic disorders.

Dr. Carmela Matrone
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegeneration
  • neurodevelopment
  • biomarkers
  • druggable targets
  • neuroinflammation
  • neuroimaging
  • genetic risk factors
  • metabolome

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Published Papers (7 papers)

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Research

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15 pages, 4268 KiB  
Article
Neuroprotective Effect of a Nutritional Supplement Containing Spearmint Extract, Forskolin, Homotaurine and Group B Vitamins in a Mouse Model of Transient Ocular Hypertension
by Andrea Satriano, Maria Luisa Laganà, Ester Licastro, Carlo Nucci, Giacinto Bagetta, Rossella Russo and Annagrazia Adornetto
Biomedicines 2023, 11(5), 1478; https://doi.org/10.3390/biomedicines11051478 - 18 May 2023
Cited by 1 | Viewed by 2447
Abstract
Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management [...] Read more.
Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management of glaucoma remains a challenge. The aim of this study was to evaluate the neuroprotective, IOP-lowering independent effects of a nutritional supplement containing forskolin, homotaurine, spearmint extract and vitamins of the B group in a model of acute glaucoma developed in mice. Glaucoma was induced in adult wild-type C57BL/6J mice by transient elevation of IOP. The dietary supplement, branded as Gangliomix® (125 mg/kg/day), was administered by oral gavage for 17 days and ocular hypertension was induced on the 10th day of treatment. A histological analysis of the retinas was performed and RGC survival was evaluated with fluorogold labeling and Brn3a immunostaining on wholemount and retinal sections. Expression of alpha-spectrin, caspase-3, PARP-1 and GFAP was studied with western blotting or immunofluorescence. A significant increase in RGC survival was reported in the retina of mice treated with the dietary supplement as compared to vehicle-treated animals. The observed neuroprotection was associated with a calpain activity decrease, reduction in caspase-3 and PARP-1 activation, and prevention of GFAP upregulation. These effects were independent from the hypotensive effects of the supplement. Altogether, our data suggest that the dietary supplementation with forskolin, homotaurine, spearmint extract and vitamins of the B group supports RGC survival and may offer beneficial effects in glaucoma patients in combination with the currently used IOP-lowering therapy. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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13 pages, 480 KiB  
Article
The Italian Framework of Bipolar Disorders in the Elderly: Old and Current Issues and New Suggestions for the Geriatric Psycho-Oncology Research
by Vincenza Frisardi, Chiara Pollorsi, Luisa Sambati, Maria Macchiarulo, Andrea Fabbo, Francesca Neviani, Marco Menchetti and Rabih Chattat
Biomedicines 2023, 11(5), 1418; https://doi.org/10.3390/biomedicines11051418 - 11 May 2023
Cited by 2 | Viewed by 2179
Abstract
Background: Older adults with mood disorders constitute a heterogeneous group in a complex spectrum interlinked with physical comorbidities. Worldwide, Bipolar disorders in older people (OABD) remain underestimated and underdiagnosed. OABD is challenging in the clinical setting and is associated with adverse outcomes (increased [...] Read more.
Background: Older adults with mood disorders constitute a heterogeneous group in a complex spectrum interlinked with physical comorbidities. Worldwide, Bipolar disorders in older people (OABD) remain underestimated and underdiagnosed. OABD is challenging in the clinical setting and is associated with adverse outcomes (increased risk of anti-social behaviour triggered by inappropriate drugs and increased incidence of health deficits, including cancer). This article aims to describe the state of the art of OABD in the Italian framework and provide a new field of research. Methods: We performed an overview of the literature, selecting our target population (over 65 years) and synthesising the main challenging issues. By exploiting the Italian database from the Minister of Health in 2021, we analysed epidemiological data in the age range 65–74 years and 75–84 years old. Results: Females showed the highest prevalence and incidence in both groups, with a regional difference across the country but more evident in the Autonomous Provinces of Bolzano and Trento for the 65–74 years range. Several projects recently focused on this topic, and the urgency to define better the epidemiological framework is mandatory. Conclusions: This study represented the first attempt to report the comprehensive Italian framework on OABD aimed at fostering research activities and knowledge. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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22 pages, 1686 KiB  
Article
Challenging the Pleiotropic Effects of Repetitive Transcranial Magnetic Stimulation in Geriatric Depression: A Multimodal Case Series Study
by Vincenzo G. Nicoletti, Francesco Fisicaro, Eugenio Aguglia, Rita Bella, Damiano Calcagno, Mariagiovanna Cantone, Carmen Concerto, Raffaele Ferri, Ludovico Mineo, Giovanni Pennisi, Riccardo Ricceri, Alessandro Rodolico, Giulia Saitta, Giulia Torrisi, Giuseppe Lanza and Manuela Pennisi
Biomedicines 2023, 11(3), 958; https://doi.org/10.3390/biomedicines11030958 - 21 Mar 2023
Cited by 9 | Viewed by 2472
Abstract
Background: Although the antidepressant potential of repetitive transcranial magnetic stimulation (rTMS), the pleiotropic effects in geriatric depression (GD) are poorly investigated. We tested rTMS on depression, cognitive performance, growth/neurotrophic factors, cerebral blood flow (CBF) to transcranial Doppler sonography (TCD), and motor-evoked potentials (MEPs) [...] Read more.
Background: Although the antidepressant potential of repetitive transcranial magnetic stimulation (rTMS), the pleiotropic effects in geriatric depression (GD) are poorly investigated. We tested rTMS on depression, cognitive performance, growth/neurotrophic factors, cerebral blood flow (CBF) to transcranial Doppler sonography (TCD), and motor-evoked potentials (MEPs) to TMS in GD. Methods: In this case series study, six drug-resistant subjects (median age 68.0 years) underwent MEPs at baseline and after 3 weeks of 10 Hz rTMS on the left dorsolateral prefrontal cortex. The percentage change of serum nerve growth factor, vascular endothelial growth factor, brain-derived growth factor, insulin-like growth factor-1, and angiogenin was obtained. Assessments were performed at baseline, and at the end of rTMS; psychocognitive tests were also repeated after 1, 3, and 6 months. Results: Chronic cerebrovascular disease was evident in five patients. No adverse/undesirable effect was reported. An improvement in mood was observed after rTMS but not at follow-up. Electrophysiological data to TMS remained unchanged, except for an increase in the right median MEP amplitude. TCD and neurotrophic/growth factors did not change. Conclusions: We were unable to detect a relevant impact of high-frequency rTMS on mood, cognition, cortical microcircuits, neurotrophic/growth factors, and CBF. Cerebrovascular disease and exposure to multiple pharmacological treatments might have contributed. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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15 pages, 2376 KiB  
Article
Combined DiI and Antibody Labeling Reveals Complex Dysgenesis of Hippocampal Dendritic Spines in a Mouse Model of Fragile X Syndrome
by Luisa Speranza, Kardelen Dalım Filiz, Sarah Goebel, Carla Perrone-Capano, Salvatore Pulcrano, Floriana Volpicelli and Anna Francesconi
Biomedicines 2022, 10(11), 2692; https://doi.org/10.3390/biomedicines10112692 - 25 Oct 2022
Cited by 6 | Viewed by 2630
Abstract
Structural, functional, and molecular alterations in excitatory spines are a common hallmark of many neurodevelopmental disorders including intellectual disability and autism. Here, we describe an optimized methodology, based on combined use of DiI and immunofluorescence, for rapid and sensitive characterization of the structure [...] Read more.
Structural, functional, and molecular alterations in excitatory spines are a common hallmark of many neurodevelopmental disorders including intellectual disability and autism. Here, we describe an optimized methodology, based on combined use of DiI and immunofluorescence, for rapid and sensitive characterization of the structure and composition of spines in native brain tissue. We successfully demonstrate the applicability of this approach by examining the properties of hippocampal spines in juvenile Fmr1 KO mice, a mouse model of Fragile X Syndrome. We find that mutant mice display pervasive dysgenesis of spines evidenced by an overabundance of both abnormally elongated thin spines and cup-shaped spines, in combination with reduced density of mushroom spines. We further find that mushroom spines expressing the actin-binding protein Synaptopodin—a marker for spine apparatus—are more prevalent in mutant mice. Previous work identified spines with Synaptopodin/spine apparatus as the locus of mGluR-LTD, which is abnormally elevated in Fmr1 KO mice. Altogether, our data suggest this enhancement may be linked to the preponderance of this subset of spines in the mutant. Overall, these findings demonstrate the sensitivity and versatility of the optimized methodology by uncovering a novel facet of spine dysgenesis in Fmr1 KO mice. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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9 pages, 2181 KiB  
Article
Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy
by Antonino Musumeci, Francesco Calì, Carmela Scuderi, Mirella Vinci, Girolamo Aurelio Vitello, Sebastiano Antonino Musumeci, Valeria Chiavetta, Concetta Federico, Greta Amore, Salvatore Saccone, Gabriella Di Rosa and Antonio Gennaro Nicotera
Biomedicines 2022, 10(9), 2276; https://doi.org/10.3390/biomedicines10092276 - 14 Sep 2022
Cited by 7 | Viewed by 1878
Abstract
Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. [...] Read more.
Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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19 pages, 2477 KiB  
Article
Repetitive Transcranial Magnetic Stimulation (rTMS) of Dorsolateral Prefrontal Cortex May Influence Semantic Fluency and Functional Connectivity in Fronto-Parietal Network in Mild Cognitive Impairment (MCI)
by Sabrina Esposito, Francesca Trojsi, Giovanni Cirillo, Manuela de Stefano, Federica Di Nardo, Mattia Siciliano, Giuseppina Caiazzo, Domenico Ippolito, Dario Ricciardi, Daniela Buonanno, Danilo Atripaldi, Roberta Pepe, Giulia D’Alvano, Antonella Mangione, Simona Bonavita, Gabriella Santangelo, Alessandro Iavarone, Mario Cirillo, Fabrizio Esposito, Sandro Sorbi and Gioacchino Tedeschiadd Show full author list remove Hide full author list
Biomedicines 2022, 10(5), 994; https://doi.org/10.3390/biomedicines10050994 - 25 Apr 2022
Cited by 24 | Viewed by 4433
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer’s disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in [...] Read more.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer’s disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases, there is still no evidence about the possible relationship between executive performances and resting-state brain FC following rTMS in patients with mild cognitive impairment (MCI). In this preliminary study, we aimed to evaluate the possible effects of rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC) in 27 MCI patients randomly assigned to two groups: one group received high-frequency (10 Hz) rTMS (HF-rTMS) for four weeks (n = 11), and the other received sham stimulation (n = 16). Cognitive and psycho-behavior scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status, Beck Depression Inventory-II, Beck Anxiety Inventory, Apathy Evaluation Scale, and brain FC, evaluated by independent component analysis of resting state functional MRI (RS-fMRI) networks, together with the assessment of regional atrophy measures, evaluated by whole-brain voxel-based morphometry (VBM), were measured at baseline, after five weeks, and six months after rTMS stimulation. Our results showed significantly increased semantic fluency (p = 0.026) and visuo-spatial (p = 0.014) performances and increased FC within the salience network (p ≤ 0.05, cluster-level corrected) at the short-term timepoint, and increased FC within the left fronto-parietal network (p ≤ 0.05, cluster-level corrected) at the long-term timepoint, in the treated group but not in the sham group. Conversely, regional atrophy measures did not show significant longitudinal changes between the two groups across six months. Our preliminary findings suggest that targeting DLPFC by rTMS application may lead to a significant long-term increase in FC in MCI patients in a RS network associated with executive functions, and this process might counteract the progressive cortical dysfunction affecting this domain. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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Review

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13 pages, 697 KiB  
Review
A Review on Music Interventions for Frontotemporal Aphasia and a Proposal for Alternative Treatments
by Vittoria Spinosa, Alessandra Vitulli, Giancarlo Logroscino and Elvira Brattico
Biomedicines 2023, 11(1), 84; https://doi.org/10.3390/biomedicines11010084 - 29 Dec 2022
Cited by 1 | Viewed by 2987
Abstract
Frontotemporal dementia (FTD) is a rare neurodegenerative disease, characterized by behavioral and language impairments. Primary progressive aphasia (PPA) is the linguistic variant of this heterogeneous disorder. To date, there is a lack of consensus about which interventions are effective in these patients. However, [...] Read more.
Frontotemporal dementia (FTD) is a rare neurodegenerative disease, characterized by behavioral and language impairments. Primary progressive aphasia (PPA) is the linguistic variant of this heterogeneous disorder. To date, there is a lack of consensus about which interventions are effective in these patients. However, several studies show that music-based interventions are beneficial in neurological diseases. This study aims, primarily, to establish the state of the art of music-based interventions designed for PPA due to FTD and, secondarily, to inform the planning of PPA-dedicated future interventions for Italian neurological institutions. The first aim is fulfilled by a review which critically screens the neurological studies examining the effects of music- and/or rhythm-based interventions, especially, on language rehabilitation in aphasic FTD. We found that only two papers fulfilled our criteria and concerned specifically aphasic patients due to FTD. Of those, one paper reported a study conducted in an Italian institution. Most of the reviewed studies focused, instead, on aphasia in post-stroke patients. The results of our review invite further studies to investigate the role of music as a valuable support in the therapy for neurodegenerative patients with language problems and in particular to PPA due to FTD. Moreover, based on this initial work, we can delineate new music-based interventions dedicated to PPA for Italian institutions. Full article
(This article belongs to the Special Issue State-of-the-Art Neurologic Disease in Italy)
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