121 research outputs found
Oxidative stress and synaptic dysfunction in rodent models of Parkinson's disease
No full textParkinson's disease (PD) is a multifactorial disorder involving a complex interplay between a variety of genetic and environmental factors. In this scenario, mitochondrial impairment and oxidative stress are widely accepted as crucial neuropathogenic mechanisms, as also evidenced by the identification of PD-associated genes that are directly involved in mitochondrial function. The concept of mitochondrial dysfunction is closely linked to that of synaptic dysfunction. Indeed, compelling evidence supports the role of mitochondria in synaptic transmission and plasticity, although many aspects have not yet been fully elucidated. Here, we will provide a brief overview of the most relevant evidence obtained in different neurotoxin-based and genetic rodent models of PD, focusing on mitochondrial impairment and synaptopathy, an early central event preceding overt nigrostriatal neurodegeneration. The identification of early deficits occurring in PD pathogenesis is crucial in view of the development of potential disease-modifying therapeutic strategies
Antiepileptic drugs on calcium currents recorded from cortical and PAG neurons: therapeutic implications for migraine
No full textCortex and periaqueductal grey (PAG) play a major role in the pathophysiology of migraine. Some antiepileptic drugs (AEDs) influence the activity of these structures by modulating high-voltage-activated (HVA) Ca(2+) channels and are effective in migraine prevention. The aim of the present study was to investigate the expression of total HVA Ca(2+) channels in cortical and PAG neurons and to study the differential action of AEDs on these channels. Isolated neurons were visually identified based on morphological criteria. HVA currents were recorded by whole-cell patch-clamp technique. The distribution ratio of L-, N-, P-, Q- and R-type HVA Ca(2+) channels was different between cortical and PAG neurons. In particular, we found that P- and Q-type HVA Ca(2+) channels were more expressed in PAG neurons than in cortical cells, whereas L- and R-type HVA Ca(2+) channels showed an opposite distribution. Interestingly, N-type HVA Ca(2+) channels were equally distributed in these two neuronal populations. A differential sensitivity to AEDs of HVA Ca(2+) channels located on cortical and PAG neurons was observed for topiramate (TPM), but not for lamotrigine (LTG) or levetiracetam (LEV). In fact, whereas both LTG and LEV were equally effective and potent in inhibiting HVA Ca(2+) currents in the two neuronal populations, TPM showed a much higher potency and efficacy in blocking these currents in PAG neurons than in cortical pyramidal cells. TPM, in fact, inhibited N-, P- and L-type channels in PAG neurons, whereas in cortical neurons this AED modulated only P- and L-type channels. Unlike the other AEDs investigated, valproic acid did not affect HVA Ca(2+) currents in cortical and PAG neurons. The negative modulation of specific subtypes of HVA Ca(2+) channels by various AEDs can restore normal electrical activity in target brain areas such as cortex and PAG, providing interesting therapeutic approaches in migraine prevention
Virus infections of honeybees Apis mellifera
No full textThe health and vigour of honeybee colonies
are threatened by numerous parasites (such
as Varroa destructor and Nosema spp.) and
pathogens, including viruses, bacteria, protozoa.
Among honeybee pathogens, viruses are
one of the major threats to the health and wellbeing
of honeybees and cause serious concern
for researchers and beekeepers. To tone down
the threats posed by these invasive organisms,
a better understanding of bee viral infections
will be of crucial importance in developing
effective and environmentally benign disease
control strategies. Here we summarize recent
progress in the understanding of the morphology,
genome organization, transmission, epidemiology
and pathogenesis of eight honeybee
viruses: Deformed wing virus (DWV) and
Kakugo virus (KV); Sacbrood virus (SBV);
Black Queen cell virus (BQCV); Acute bee
paralysis virus (ABPV); Kashmir bee virus
(KBV); Israeli Acute Paralysis Virus (IAPV);
Chronic bee paralysis virus (CBPV). The
review has been designed to provide researchers
in the field with updated information
about honeybee viruses and to serve as a starting
point for future research
RNA extraction method for the PCR detection of hepatitis A virus in shellfish
No full textViruses are the leading cause of foodborne illness associated with the consumption of raw or slightly-cooked
contaminated shellfish. This study evaluated the E.Z.N.A. Mollusc RNA extraction and purification kit for the
detection of HAV in shellfish. The E.Z.N.A. method, based on the cationic detergent, cetyltrimethyl
ammonium bromide, in conjunction with a selective RNA binding silica matrix, efficiently isolated viral RNA
with a detection limit of 1 TCID50/ml by hemi-nested PCR. This method proved to be faster and less
expensive than PEG precipitation-based procedures. It is also technically undemanding, requiring no
extensive processing steps or excess manipulation, minimizing RNA degradation and ensuring the absence of
PCR inhibitors. The E.Z.N.A. method applied to HAV screening of shellfish samples from the Apulian region,
revealed a high level of contamination. These results confirm that conventional faecal indicators are
unreliable for demonstrating the presence or absence of viruse
Classification of Microarray Data with Factor Mixture Models.
No full textThe classification of few tissue samples on a very large
number of genes represents a non-standard problem in statistics but a
usual one in microarray expression data analysis. In fact, the dimension
of the feature space (the number of genes) is typically much greater
than the number of tissues. We consider high-density oligonucleotide
microarray data, where the expression level is associated to an ‘abso-
lute call’, which represents a qualitative indication of whether or not a
transcript is detected within a sample. The ‘absolute call’ is generally
not taken in consideration in analyses.
Results: In contrast to frequently used cluster analysis methods to
analyze gene expression data, we consider a problem of classification
of tissues and of the variables selection. We adopted methodologies
formulated by Ghahramani and Hinton and Rocci and Vichi for simul-
taneous dimensional reduction of genes and classification of tissues;
trying to identify genes (denominated ‘markers’) that are able to distin-
guish between two known different classes of tissue samples. In this
respect, we propose a generalization of the approach proposed by
McLachlan et al. by advising to estimate the distribution of log LR statis-
tic for testing one versus two component hypothesis in the mixture
model for each gene considered individually, using a parametric
bootstrap approach. We compare conditional (on ‘absolute call’) and
unconditional analyses performed on dataset described in Golub et al.
We show that the proposed techniques improve the results of classi-
fication of tissue samples with respect to known results on the same
benchmark dataset.
Availability: The software of Ghahramani and Hinton is written in
Matlab and available in ‘Mixture of Factor Analyzers’ on http://www.
gatsby.ucl.ac.uk/zoubin/software.html while the software of Rocci
and Vichi is available upon request from the author
Detection of a honeybee iflavirus with intermediate charateristics between kakugo virus and deformed wing virus
No full textIflavirus RNA was detected in honeybee colonies displaying unduly aggressive behavior and with no evidence of more phological alterations. Sequence analysis of the RNA-dependent RNA polymerase (RdRp) revealed that the iflavirus strain was more similar (>99% aa) to Deformed Wing Virus (DWV), that has been associated with morphological alterations in bees, rather than to the newly-described Kakugo Virus (KV) (about 95% aa), that has been associated with increased aggressiveness. Therefore, the iflavirus strain detected in the Italian hives genetically resembled DWV but was apparently associated with a KV-Llike phenotype. RT-PCR detected the iflavirus RNA in the abdomen of the workers, and only in one case was the virus detected in the head. No viral RNA was detected in the drones, a pattern of virus distribution across the honeybee casts that is in apparent conflict with tire higher rates of infestation of drones by the mite Varroa distructor. The identification of a virus with apparently intermediate features between DWV and KV open new perspectives on the patho-biological role of iflaviruses in honeybees
Ochratoxin A in avicultural meat production: chemical and histological effects
No full textOchratoxins are fungal secondary metabolites that may contaminate various foods and beverages. Ochratoxins may undergo bio-concentration in some animal tissues/organs and reach concentrations in meat products that are not acceptable for human consumption. The intake of ochratoxins by humans may result in typical syndromes (nephrotoxicity, carcinogenicity, teratogenicity and immunotoxicity) and has been associated with Balkan Endemic Nephropathy. In this study we evaluated the effects and the dynamics of accumulation of ochratoxin A in the organs and tissues after prolonged exposure (40 days) in broilers through their productive cycle. Cytological and histological examinations revealed severe alterations in the hepatic and renal tissues only in animals fed with high dosages (200 μg/kg) of ochratoxin A. But the toxin was detected at levels of 0.78-2.15 μg/kg at day 10 in the tissues of animals that were given feed containing 100 μg/kg, a dosage of ochratoxin A admitted by the current EU recommendation and Italian legislation, and that did not display gross or histo-pathological lesions. Consumption of ochratoxin A-contaminated avian meat, containing such ochratoxin concentrations, could pose a health risk for some human categories. Intensification of surveillance for fungal toxins in animal feeds is advisable in order to understand and prevent this risk
R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice
No full textDominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are a common genetic cause of Parkinson's disease (PD). The importance of the R1441 residue in the pathogenesis is highlighted by the identification of three distinct missense mutations. To investigate the pathogenic mechanism underlying LRRK2 dysfunction, we generated a knockin (KI) mouse in which the R1441C mutation is expressed under the control of the endogenous regulatory elements. Homozygous R1441C KI mice appear grossly normal and exhibit no dopaminergic (DA) neurodegeneration or alterations in steady-state levels of striatal dopamine up to 2 years of age. However, these KI mice show reductions in amphetamine (AMPH)-induced locomotor activity and stimulated catecholamine release in cultured chromaffin cells. The introduction of the R1441C mutation also impairs dopamine D2 receptor function, as suggested by decreased responses of KI mice in locomotor activity to the inhibitory effect of a D2 receptor agonist, quinpirole. Furthermore, the firing of nigral neurons in R1441C KI mice show reduced sensitivity to suppression induced by quinpirole, dopamine, or AMPH. Together, our data suggest that the R1441C mutation in LRRK2 impairs stimulated dopamine neurotransmission and D2 receptor function, which may represent pathogenic precursors preceding dopaminergic degeneration in PD brains
Centrality of striatal cholinergic transmission in Basal Ganglia function
No full textWork over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction. Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson's disease and dystonia. Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders
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