CNR Institute of Neurological Sciences

Catania, Italy

CNR Institute of Neurological Sciences

Catania, Italy
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Bassani S.,CNR Institute of Neuroscience | Cingolani L.,University College London | Cingolani L.,Italian Institute of Technology | Valnegri P.,CNR Institute of Neuroscience | And 7 more authors.
Neuron | Year: 2012

Mutations in TSPAN7-a member of the tetraspanin protein superfamily-are implicated in some forms of X-linked intellectual disability. Here we show that TSPAN7 overexpression promotes the formation of filopodia and dendritic spines in cultured hippocampal neurons from embryonic rats, whereas TSPAN7 silencing reduces head size and stability of spines and AMPA receptor currents. Via its C terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking. These findings indicate that, in hippocampal neurons, TSPAN7 regulates AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability. Mutations in TSPAN7 protein cause human intellectual disability. Bassani et al. now find that TSPAN7 regulates trafficking of essential receptor proteins to neuron surfaces and that absence impairs neuronal maturation in young animals, potentially underlying this intellectual disability. © 2012 Elsevier Inc.

D'Alessandro G.,Center for Osteopathic Medicine Collaboration | Cerritelli F.,Center for Osteopathic Medicine Collaboration | Cerritelli F.,University of Chieti Pescara | Cortelli P.,University of Bologna | Cortelli P.,CNR Institute of Neurological Sciences
Frontiers in Neuroscience | Year: 2016

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate "reading system" able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways. © 2016 D'Alessandro, Cerritelli and Cortelli.

Ciranna L.,University of Catania | Catania M.V.,CNR Institute of Neurological Sciences | Catania M.V.,Laboratory of Neurobiology
Frontiers in Cellular Neuroscience | Year: 2014

Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD. © 2014 Ciranna and Catania.

Costa L.,University of Catania | Trovato C.,Research and Therapy Institution IRCCS Oasi Maria Santissima | Musumeci S.A.,Research and Therapy Institution IRCCS Oasi Maria Santissima | Catania M.V.,Research and Therapy Institution IRCCS Oasi Maria Santissima | And 2 more authors.
Hippocampus | Year: 2012

We have studied the effects of 5-HT 1A and 5-HT 7 serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT 1A/5-HT 7 receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT 1A receptor agonist 8-OH PIPAT and blocked by the 5-HT 1A antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT 7 receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT 7 receptors, we used the compound LP-44, which is considered a selective 5-HT 7 agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT 1A and 5-HT 7 receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT 1A receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT 7 receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the need for new selective agonists of 5-HT 7 receptors. © 2011 Wiley Periodicals, Inc.

Verrotti A.,University of Perugia | Filippini M.,CNR Institute of Neurological Sciences | Matricardi S.,University of Chieti Pescara | Agostinelli M.F.,University of Chieti Pescara | Gobbi G.,CNR Institute of Neurological Sciences
Brain and Cognition | Year: 2014

Benign Epilepsy with centrotemporal spikes (BECTS) is considered a benign type of epilepsy; nevertheless a significant number of children present clear and heterogeneous cognitive deficits such as memory disturbances. Thus far, evidence about memory impairment has been less than conclusive. To clarify the quality of memory functioning in BECTS children, an analysis of existing findings has been conducted trying to identify the type of memory deficits and their underlying factors. Short- and long-term declarative memory are impaired in BECTS children, with both verbal and non-verbal material; co-occurrence of attentional, linguistic and behavioral disturbances is reported. In children with continuous spikes and waves during the slow-wave sleep pattern the normal downscaling of slow-wave activity is absent, disrupting plastic brain processes of sleep-related memory consolidation. In BECTS children, NREM sleep interictal epileptiform discharges (IED) may interfere in the dialogue between temporal and frontal cortex, causing declarative memory deficits: the role of NREM sleep IED acquires a special importance, leading to methodological guidance and suggesting aims for future researches in the field of childhood neuroscience. © 2013 Elsevier Inc.

Partinen M.,Vitalmed Research Center | Partinen M.,University of Helsinki | Kornum B.R.,Glostrup Hospital | Plazzi G.,University of Bologna | And 5 more authors.
The Lancet Neurology | Year: 2014

Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger. © 2014 Elsevier Ltd.

Mazzatenta D.,CNR Institute of Neurological Sciences | Zoli M.,CNR Institute of Neurological Sciences | Mascari C.,CNR Institute of Neurological Sciences | Pasquini E.,Azienda USL | Frank G.,CNR Institute of Neurological Sciences
Spine | Year: 2014

STUDY DESIGN.: This study evaluates a series of consecutive endoscopic endonasal odontoidectomies performed since 2008 in our center. OBJECTIVE.: The aim of the study was to analyze the outcome and the surgical technique to enlighten advantages and limitations of this procedure. SUMMARY OF BACKGROUND DATA.: Odontoidectomy represents the treatment of choice in selected cases of basilar invagination. Transoral-transpharyngeal odontoidectomy is the "gold standard" and more experienced technique. Recently, the endoscopic endonasal approach has been proposed as an alternative route. METHODS.: All patients underwent a pre- and postoperative evaluation of neurological status using physical neurological examination, assessment of American Spinal Injury Association impairment scale score, and neurophysiological investigations. Pre- and postoperative neuroradiological examinations consisted of magnetic resonance imaging, computed tomography, and radiography in flexion and extension. Surgical complications, time of orotracheal extubation and of resumption of oral feeding after surgery were considered, basing on medical records. RESULTS.: The series is composed of 5 cases. All cases presented a progressive tetraparesis despite a posterior occipitocervical arthrodesis. Two patients presented with irreducible atlantoaxial subluxation in Down syndrome, whereas the others presented with an atlanto-occipital malformation with platybasia and basilar invagination. No complications were observed. In all except one case, orotracheal intubation was removed immediately at the end of surgery. Oral feeding was resumed 1 day after surgery in all but one case that initially required an orogastric tube. At follow-up (mean: 34.2 mo; range: 3-57 mo), neurological symptoms have been shown to improve in 2 cases and stabilization, arresting the neurological worsening, in 3 cases. CONCLUSION.: Endoscopic endonasal odontoidectomy resulted in a safe, effective, and well-tolerated procedure. From our experience, we conclude that the different approaches for odontoidectomy should be considered to be complementary rather than alternative: the endonasal endoscopic can be advantageous in selected cases presenting some anatomical conditions related (micrognathia and macroglossia) to the oral cavity and to high position of the odontoid.Level of Evidence: 4 © 2014 Lippincott Williams & Wilkins.

Tomson T.,Karolinska Institutet | Battino D.,CNR Institute of Neurological Sciences
Handbook of Experimental Pharmacology | Year: 2011

It is well established that children exposed to antiepileptic drugs (AEDs) in utero have an increased risk of adverse pregnancy outcomes including foetal growth retardation, major congenital malformations and impaired postnatal cognitive development. However, due to the significant maternal and foetal risks associated with uncontrolled epileptic seizures, AED treatment is generally maintained during pregnancy in the majority of women with active epilepsy. The prevalence of major malformations in children exposed to AEDs has ranged from 4 to 10%, 2-4 times higher than in the general population. More recent studies suggest a smaller increase in malformation rates. Malformation rates have consistently been higher in association with exposure to valproate than with carbamazepine and lamotrigine. Some prospective cohort studies also indicate reduced cognitive outcome in children exposed to valproate compared to carbamazepine and possibly lamotrigine. Information on pregnancy outcomes with newer generation AEDs other than lamotrigine are still insufficient. © 2011 Springer-Verlag Berlin Heidelberg.

DiMauro S.,York College | Schon E.A.,York College | Carelli V.,CNR Institute of Neurological Sciences | Hirano M.,York College
Nature Reviews Neurology | Year: 2013

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category - defects of mtDNA maintenance - combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot-Marie-Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. © 2013 Macmillan Publishers Limited. All rights reserved.

Alessandria M.,University of Bologna | Provini F.,University of Bologna | Provini F.,CNR Institute of Neurological Sciences
Frontiers in Neurology | Year: 2013

In recent years, a growing body of evidence suggests that periodic limb movements during sleep (PLMS) are associated with hypertension, cardiovascular, and cerebrovascular risk. However, several non-mutually exclusive mechanisms may determine a higher cardiovascular risk in patients with PLMS and the link between the two remains controversial. Prospective data are scant and the temporal relationship between PLMS and acute vascular events is difficult to ascertain because although PLMS may lead to acute vascular events such as stroke, stroke may also give rise to PLMS. This article describes the clinical and polygraphic features of PLMS and examines the literature evidence linking PLMS with an increased risk for the development and progression of cardiovascular diseases, discussing the possible pathways of this association. © 2013 Alessandria and Provini.

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