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Acid-sensing ion channels (ASICs) are widely expressed in the mammalian central nervous system where they play a key role in synaptic transmission and in specific forms of memory. On the other hand, ASICs can be persistently active under pathological conditions contributing to neuronal damage in ischemic stroke, brain trauma, epilepsy and Parkinson’s disease. However, to date no experimental evidence has linked ASICs to Alzheimer’s disease (AD). Aim of the present work was to investigate, in CA1 pyramidal neurons, the possible involvement of ASIC1a in the Aβ-mediated effect on metabotropic glutamate (mGlu) receptor dependent transmission. We found that, in slices pretreated with Aβ, the pharmacological blockade of ASIC1a restored the increased intrinsic excitability following group I mGlu receptor activation. This suggests that, under certain conditions, ASIC1a might further contribute to the Aβ-related depolarizing response. We have recently demonstrated that ASIC1a is also involved long-term depression (LTD) induced either by low-frequency stimulation or by application of the group I mGlu receptor agonist DHPG. Here, we have shown that psalmotoxin-1, a selective blocker of ASIC1a, rescued the DHPG-LTD facilitation associated with genetic and non-genetic models of AD. Overall, these results suggest that a functional coupling between ASIC1a and mGlu receptors occurs and might contribute to the synaptic alterations associated with AD. [ABSTRACT FROM AUTHOR]

Background and purpose:Reactive oxygen species (ROS) have been postulated to play a crucial role in the pathogenesis of ischaemia-reperfusion injury. Among these, hydrogen peroxide (H2O2) is known to be a toxic compound responsible for free-radical-dependent neuronal damage. In recent years, however, the ‘bad reputation’ of H2O2 and other ROS molecules has changed. The aim of this study was to assess the protective role of H2O2 and modification in its endogenous production on the electrophysiological and morphological changes induced by oxygen/glucose deprivation (OGD) on CA1 hippocampal neurons.Experimental approach:Neuroprotective effects of exogenous and endogenous H2O2 were determined using extracellular electrophysiological recordings of field excitatory post synaptic potentials (fEPSPs) and morphological studies in a hippocampal slice preparation. In vitro OGD was delivered by switching to an artificial cerebrospinal fluid solution with no glucose and with oxygen replaced by nitrogen.Key results:Neuroprotection against in vitro OGD was observed in slices treated with H2O2 (3 mM). The rescuing action of H2O2 was mediated by catalase as pre-treatment with the catalase inhibitor 3-amino-1,2,4-triazole blocked this effect. More interestingly, we showed that an increase of the endogenous levels of H2O2, due to a combination of an inhibitor of the glutathione peroxidase enzyme and addition of Cu,Zn-superoxide dismutase in the tissue bath, prevented the OGD-induced irreversible depression of fEPSPs.Conclusions and implications:Taken together, our results suggest new possible strategies to lessen the damage produced by a transient brain ischaemia by increasing the endogenous tissue level of H2O2.British Journal of Pharmacology (2008) 153, 1022–1029; doi:10.1038/sj.bjp.0707587; published online 28 January 2008 [ABSTRACT FROM AUTHOR]

Objective: DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD.Methods: This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT.Results: Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD.Conclusions: In the absence of DAT-SPECT, the pattern of resting tremor can be considered a useful investigation for differentiating rDIP from PD. [ABSTRACT FROM AUTHOR]

Selective composite membranes with high and controlled porosity have been fabricated using patterned silicon microsieves as support and nanoporous polystyrene- block -poly(ethylene oxide) (PS- b -PEO) membranes as selective layer. The desired morphology of the block copolymer layer is obtained by a supramolecular approach based on the hydrogen bonding of the PEO block with resorcinol. The formation of PS- b -PEO/resorcinol complexes allows to easily control the self-assembly of the block copolymer and to obtain normally oriented PEO/resorcinol nanocylinders by spin coating PS- b -PEO/resorcinol solutions. In a further step resorcinol works as a porogen and by its selective dissolution densely packed, normally oriented nanochannels coated by PEO chains have been obtained. These hydrophilic nanochannels have a diameter of approximately 20 nm and cross the membranes from top to bottom. The nanoporous polymer layer is crack-free and well adheres to the support microsieve. The composite membrane is permeable to methylene blue while blocks larger molecules, such as bovine serum albumin. [ABSTRACT FROM AUTHOR]

Abstract: An increased R2 recovery component of the blink reflex (R2-BRrc) has been observed in Parkinson's disease (PD), cranio-cervical dystonia, dystonic tremor and essential tremor with associated resting tremor (rET), while the BRrc was reported normal in patients with essential tremor (ET). Distinguishing rET from tremor dominant PD (tPD) may be challenging especially in the first stages of the diseases, in the absence of DAT-SPECT investigation. We evaluated the possible usefulness of BRrc for differentiating subjects with de novo tPD from those with rET. We investigated R2-BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 ms in 11 participants with tPD, 10 with rET and 20 healthy controls. All participants underwent DAT-SPECT and cardiac MIBG scintigraphy. R2 recovery was significantly enhanced in tPD compared to controls at all investigated ISIs (p < 0.001), while in subjects with rET patients BRrc was significantly increased compared to controls at ISI 150, 200, 300, 400, 500 and 750 ms (p < 0.001). At ISI 100 R2-BRrc distinguished patients participants with de novo tPD from those with rET with a sensitivity, specificity and accuracy of 100%. Our findings demonstrate the usefulness of BRrc for differentiating de novo tPD from rET. [Copyright &y& Elsevier]

For many years after its discovery, hydrogen peroxide (H₂O₂) was viewed as a toxic molecule to human tissues; however, in light of recent findings, it is being recognized as an ubiquitous endogenous molecule of life as its biological role has been better elucidated. Indeed, increasing evidence suggests that H₂O₂ may act as a second messenger with a pro-survival role in several physiological processes. In addition, our group has recently demonstrated neuroprotective effects of H₂O₂ on in vitro and in vivo ischaemic models through a catalase (CAT) enzyme-mediated mechanism. Therefore, the present review summarizes experimental data supporting a neuroprotective potential of H₂O₂ in ischaemic stroke that has been principally achieved by means of pharmacological and genetic strategies that modify either the activity or the expression of the superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT enzymes, which are key regulators of H₂O₂ metabolism. It also critically discusses a translational impact concerning the role played by H₂O₂ in ischaemic stroke. Based on these data, we hope that further research will be done in order to better understand the mechanisms underlying H₂O₂ functions and to promote successful H₂O₂ signalling based therapy in ischaemic stroke. [ABSTRACT FROM AUTHOR]

Abstract: Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinson’s disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD patients was significantly higher than that of patients with ET (p = 0.002), whereas burst duration and frequency were significantly higher in ET than in PD group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed some overlap of these electrophysiological values with values from patients with ET. By contrast, rest tremor pattern showed no overlap between the two diseases, because all patients with ET presented a synchronous pattern whereas PD patients had an alternating pattern (p < 0.001), a finding that differentiated the patients on an individual basis. The electromyographic pattern of rest tremor may help to differentiate PD from ET. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case report on lamotrigine therapy for paroxymal dysarthria which was caused by multiple sclerosis (MS).

Abstract: DYT1 dystonia is a movement disorder caused by a deletion in the C-terminal of the protein torsinA. It is unclear how torsinA mutation might disrupt cellular processes encoding motor activity, and whether this impairment occurs in specific brain regions. Here, we report a selective impairment of corticostriatal synaptic plasticity in knock-in mice heterozygous for Δ-torsinA (Tor1a+/Δgag mice) as compared to controls (Tor1a+/+ mice). In striatal spiny neurons from Tor1a+/Δgag mice, high-frequency stimulation failed to induce long-term depression (LTD), whereas long-term potentiation (LTP) exhibited increased amplitude. Of interest, blockade of D2 dopamine receptors (D2Rs) increased LTP in Tor1a+/+ mice to a level comparable to that measured in Tor1a+/Δgag mice and normalized the levels of potentiation across mouse groups. A low-frequency stimulation (LFS) protocol was unable to depotentiate corticostriatal synapses in Tor1a+/Δgag mice. Muscarinic M1 acetylcholine receptor (mAChR) blockade rescued plasticity deficits. Additionally, we found an abnormal responsiveness of cholinergic interneurons to D2R activation, consisting in an excitatory response rather than the expected inhibition, further confirming an imbalance between dopaminergic and cholinergic signaling in the striatum. Conversely, synaptic activity and plasticity in the CA1 hippocampal region were unaltered in Tor1a+/Δgag mice. Importantly, the M1 mAChR-dependent enhancement of hippocampal LTP was unaffected in both genotypes. Similarly, both basic properties of dopaminergic nigral neurons and their responses to D2R activation were normal. These results provide evidence for a regional specificity of the electrophysiological abnormalities observed and demonstrate the reproducibility of such alterations in distinct models of DYT1 dystonia. [Copyright &y& Elsevier]

Abstract: mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depression and in susceptibility to convulsive seizures. In spite of these potential clinical implications, little is known on the mechanisms that regulate mGlu7-receptor signaling. Here we show that mGlu7 receptor-dependent signaling pathways were regulated in a complementary manner by different GRK subtypes, with GRK4 affecting the adenylyl cyclase and the JNK pathways, and GRK2 selectively affecting the ERK1/2 pathway. Additionally we found that the two isoforms of non-visual arrestins, i.e. β-arrestin1 and β-arrestin2, exerted opposite effects on mGlu7-receptor signaling, with β-arrestin1 positively modulating ERK1/2 and inhibiting JNK, and β-arrestin2 doing the opposite. This represents a remarkable example of “reciprocal regulation” of receptor signaling by the two isoforms of β-arrestin. Finally we found that β-arrestin1 amplified mGlu7 receptor-dependent ERK1/2 activation in response to L-AP4 (an orthosteric agonist), but not in response to AMN082 (an atypical mGlu7-receptor allosteric agonist). The different effect of β-arrestin1 on L-AP4- and AMN082-stimulated ERK1/2 phosphorylation is in line with the emerging concept of β-arrestin-biased agonists. The present study may open new perspectives in elucidating the physio-pathological roles of the mGlu7 receptor and may provide new insights for the possibility to develop specific (biased) agonists that can selectively activate different signaling pathways. [Copyright &y& Elsevier]

Graphical abstract Highlights • The photodegradation of four micro-contaminants has been studied. • Hybrid magnetic materials have been employed in photo-Fenton like process. • TiO 2 homemade shown better performances than P25. • Micro-contaminants degradation has been attained under solar irradiation. Abstract This work reports on the light-induced heterogeneous photodegradation of four micro-contaminants (MCs): Carbamazepine (C), Flumequine (F), Ibuprofen (I), and Sulfamethoxazole (S), using two different heterogeneous advanced oxidation processes. The first one is the semiconductor photocatalysis, run in the presence of the suspension of a home prepared TiO 2 (TiO 2 HP); the second one is an heterogeneous photo-Fenton process run in the presence of a hybrid magnetic nanomaterial (MB3) with an iron oxides core and an organic shell made of bio-based substances (BBS) isolated from urban biowaste. The two materials work upon two different mechanisms and were already tested (and the action mechanism hypothesized) at the lab scale under model conditions: TiO 2 acts as photocatalyst through the photo-generation of hole/electron pairs able to give rise to oxidation and reduction reactions, whereas hybrid magnetic nanomaterial acts in the presence of H 2 O 2 by a photo-Fenton like mechanism. The results evidenced the better performances of TiO 2 HP (also better than the well-known reference TiO 2 P25). Preliminary photodegradation experiments carried out in a pilot plant under natural solar radiation confirmed the good results obtained with TiO 2 HP. Moreover, in the adopted experimental conditions, the Fe(II) leached from MB3 can be considered as responsible of the MCs degradation through a homogeneous photo-Fenton reaction, where MB3 act as iron reservoir. [ABSTRACT FROM AUTHOR]

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na + channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca 2+ and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to correlate the brain atrophy with serum levels of anti-GM1 antibodies in patients with relapsing-remitting multiple sclerosis (RRMS). Methods Plasma sample from 52 patients with RRMS and 65 healthy controls were examined for anti-GM1 antibodies. Patients with RRMS underwent to MRI study with automated method called SIENAX that calculated an estimate of gray matter (GMV) and white matter (WMV) volumes. Results The percentage of RRMS patients with increased anti-GM1 was 37.8%. Elevated levels of anti-GM1 antibodies did not correlate with brain atrophy. Conclusions Anti-GM1 antibodies do not represent a marker of axonal damage in patients with RRMS. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) can be considered as a brain multisystemic disease arising from dysfunction in several neural networks. The principal aim of this study was to assess whether large-scale structural topological network changes are detectable in PD patients who have not been exposed yet to dopaminergic therapy (de novo patients). Twenty-one drug-naïve PD patients and thirty healthy controls underwent a 3T structural MRI. Next, Diffusion Tensor Imaging (DTI) and graph theoretic analyses to compute individual structural white-matter (WM) networks were combined. Centrality (degree, eigenvector centrality), segregation (clustering coefficient), and integration measures (efficiency, path length) were assessed in subject-specific structural networks. Moreover, Network-based statistic (NBS) was used to identify whether and which subnetworks were significantly different between PD and control participants. De novo PD patients showed decreased clustering coefficient and strength in specific brain regions such as putamen, pallidum, amygdala, and olfactory cortex compared with healthy controls. Moreover, NBS analyses demonstrated that two specific subnetworks of reduced connectivity characterized the WM structural organization of PD patients. In particular, several key pathways in the limbic system, basal ganglia, and sensorimotor circuits showed reduced patterns of communications when comparing PD patients to controls. This study shows that PD is characterized by a disruption in the structural connectivity of several motor and non-motor regions. These findings provide support to the presence of disconnectivity mechanisms in motor (basal ganglia) as well as in non-motor (e.g., limbic, olfactory) circuits at an early disease stage of PD. Hum Brain Mapp 37:4500-4510, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Introduction REM sleep behavior disorder (RBD) is a common non motor feature of Parkinson's Disease (PD) affecting about half the patients with this disease. Distinct structural brain tissue abnormalities have been reported in several regions modulating REM sleep of the patients with idiopathic RBD. At the present time, there are no conventional MRI studies investigating patients with PD associated with RBD. Methods Herein, we used voxel-based morphometry (VBM) to detect the neuroanatomical profile of PD patients with and without RBD. Optimized VBM was applied to the MRI brain images in 11 PD patients with RBD (PD-RBD), 11 PD patients without RBD (PD) and 18 age-and sex-matched controls. To corroborate VBM findings we used automated volumetric method (FreeSurfer) to quantify subcortical brain regions volumes. Patients and controls also underwent DAT-SPECT and cardiac MIBG scintigraphies. Results The VBM analysis showed markedly reduced gray matter volume in the right thalamus of PD-RBD patients in comparison with PD patients and controls. Automatic thalamic segmentation in PD-RBD patients showed a bilaterally reduced thalamic volume as compared with PD patients or controls. All PD patients (with and without RBD) showed a reduced tracer uptake on DAT-SPECT and cardiac MIBG scintigraphies as compared to controls. Conclusions Our findings suggest that the presence of RBD symptoms in PD patients is associated with a reduced thalamic volume suggesting a pathophysiologic role of the thalamus in the complex circuit causing RBD. [ABSTRACT FROM AUTHOR]

Abstract: CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for the treatment of Alzheimer's disease. The aim of the present study was to characterize the electrophysiological and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show that CHF5074 inhibits in a dose-dependent manner the current-evoked repetitive firing discharge in CA1 pyramidal neurons. This result is paralleled by a dose-dependent reduction of field excitatory post-synaptic potentials with no effect on the paired-pulse ratio. The effects of CHF5074 were not mediated by AMPA or NMDA receptors, since the inward currents induced by local applications of AMPA and NMDA remained constant in the presence of this compound. We also suggest a possible activity of CHF5074 on ASIC1a receptor since ASIC1a-mediated current, evoked by application of a pH 5.5 solution, is reduced by pretreatment with this compound. Moreover, we demonstrate that CHF5074 treatment is able to counteract in hippocampal slices the OGD-induced increase in alanine, lactate and acetate levels. Finally, CHF5074 significantly reduced the apoptosis in hippocampal neurons exposed to OGD, as revealed by cleaved-caspase-3 immunoreactivity and TUNEL staining. Overall, the present work identifies novel mechanisms for CHF5074 in reducing metabolic acidosis, rendering this compound potentially useful also in conditions of brain ischemia. [Copyright &y& Elsevier]

Highlights: [•] The mechanism underlying the effects of modafinil on the DAergic neurons is proposed. [•] Modafinil potentiates DAergic transmission via DAT inhibition. [•] This mechanism of action explains its usefulness in the clinical setting. [Copyright &y& Elsevier]

ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer's disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aβ-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aβ oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism. [ABSTRACT FROM AUTHOR]

Background Cerebellar dysfunction is common in patients with multiple sclerosis (MS). However, neuropsychological studies of this clinical feature are lacking. Objective We investigate the neuropsychological features in relapsing-remitting MS (RR-MS) patients with and without cerebellar dysfunction. Methods Twenty-one RR-MS patients with cerebellar dysfunction (RR-MSc), characterized by prevalent ataxic gait and nystagmus, and 21 RR-MS patients without any cerebellar manifestation (RR-MSnc) pair-matched for demographical and clinical variables were studied. All patients from each group underwent an extensive battery of neuropsychological tests. Magnetic resonance imaging analysis included hyperintense fast fluid-attenuated inversion-recovery lesion load in the whole brain as well as in the four lobes separately. Results Any significant differences were detected in total and regional lesion load measurements between the two groups. RR-MSc group performed equally as well as the RR-MSnc group on many of the cognitive exploration measures. Nevertheless, the RR-MSc group performed more poorly than the RR-MSnc group on attention tests (Symbol Digit Modalities Test) and verbal fluency tests (Controlled Oral Word Association Test); neither of the test results proved to be affected by regional lesion loads. Conclusion These results highlight the importance of considering cognitive deficits associated with the presence of cerebellar symptoms in RR-MS. [ABSTRACT FROM AUTHOR]

Abstract: Caspase-9 is a primary effector CASP that executes programmed cell death, which plays an important role in the development of multiple sclerosis (MS). Polymorphisms in the CASP-9 gene may influence its activity, thereby modulating the susceptibility to MS. To test this hypothesis, we evaluated a SNP in the CASP-9 gene in a set of Italian patients from Southern Italy and healthy control subjects. Our results suggest that the presence of the G/G genotype represents a higher risk factor in our MS population and a differential production of CASP-9 might be a contributory factor in determining the severity of MS. [Copyright &y& Elsevier]

Abstract: Lymphocyte and monocyte brain infiltration determines inflammation in multiple sclerosis. The trafficking of these cells into the CNS results from the VLA-4 binding with its ligand on brain endothelial cells. MS patients treated with an antibody against the alpha-4 subunit, which inhibits this interaction, prevents brain lesion development. We investigated the association between VLA-4 gene polymorphisms and MS in a study on 275 patients and 255 controls. No differences were detected, thus suggesting that these polymorphisms are not a significant genetic risk factor for susceptibility to MS in Italy. [Copyright &y& Elsevier]

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing–remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational-level matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) ( P = 0.005). Furthermore, a significant ( P = 0.013) interaction effect between ‘MS-status’ and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients. [ABSTRACT FROM AUTHOR]

The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex. It contains a rich array of brain terminals, which modulate the visual signals to the cortex. Several data have documented that beside cholinergic, GABA-nergic, istaminergic, serotoninergic, and glutamatergic signals, the LGN contains also fibers and interneurons expressing the enzyme that produces nitric oxide (NO). Here, we review the documented physiological roles of NO in the transmission of visual inputs to the cortex and in the processes of activity-dependent refinement of LGN connections. Moreover we focus on the recently suggested role of NO in processes of neurotoxicity in the LGN. Particular relevance is given to studies documenting that, through an excitotoxic cascade, NO triggers apoptosis in the LGN of new-born rats deprived of vision in one eye. Data are also discussed on a possible role of NO in the mechanisms of LGN neuronal loss induced by glaucoma. We believe that a better understanding of the role of NO in the LGN may contribute to discover new experimental strategies for the treatment of degenerative ophthalmic diseases. [Copyright &y& Elsevier]

Immunoelectron microscopy analysis of brain tissue sections and rat-specific sandwich ELISA allowed the localization of interleukin-1β (IL-1β) immunoreactivity in the mitochondria and cytosol of neocortical tissue preparations from the brain of naive, untreated, rats and rats receiving a single daily injection into one lateral cerebral ventricle (i.c.v.) of bovine serum albumin (BSA; 100 ng/day) for seven consecutive days. Interestingly, seven days i.c.v. treatment with the HIV-1 coat protein gp120 (100 ng/day) enhances IL-1β immunoreactivity in the cellular fractions studied. Elevation of mitochondrial immunoreactive IL-1β levels seems to originate from the conversion operated by the interleukin converting enzyme (ICE) of mitochondrial pro-IL-1β; in fact, IL-1β increases reported in the ELISA experiments were paralleled by a decrease of the mitochondrial pro-IL-1β 31-kDa band in conjunction with enhanced expression of the p20 component of activated ICE. In conclusion, the present results demonstrate that gp120-enhanced neocortical expression of IL-1β originates, at least in part, from in situ cleavage of mitochondrial pro-IL-1β and suggest that this, together with the central role of the mitochondrion in the expression of programmed cell death, may be important for apoptosis induced by the viral coat protein in the brain of rats. [ABSTRACT FROM AUTHOR]