Valproic acid neuroprotection in 6-OHDA lesioned rat, a model for parkinson's disease

Background: Valproic acid (VPA) a long standing anti-epileptic and anti-manic drug has been recently investigated as a neuroprotective molecule, in relation to its action as an inhibitor of histone deacetylases (HDACs), favoring relaxed configuration of chromatin and thus promoting gene transcription. Methods: In the present study, chronic administration of VPA added to the diet, was tested for neuroprotection in a rat model of Parkinson's disease. The model consists of multiple injections of the dopaminergic toxin, 6-hydroxydopamine (6-OHDA), unilaterally in the striatum with consequent degeneration of the dopaminergic neurons originating the nigro-striatal pathway. This model of neurodegeneration is widely used as a reliable animal model for Parkinson's disease (PD). Results: Chronic VPA administration significantly reduced degeneration of dopaminergic neurons in the substantia nigra, and of dopaminergic terminals in the striatum, in rats subjected to the unilateral lesion of the nigrostriatal pathway. VPA treatment was also able to increase α-synuclein expression in the substantia nigra and to counteract the lesion-dependent decrease of the protein in the substantia nigra itself and in the striatum. Conclusions: Present data, which follow previous results obtained in the rotenone rat model of nigrostriatal degeneration, allow to propose VPA as a treatment to be tested for its effectiveness in other animal models of parkinsonism, in view of possible translation to patients

Characterization of DNA methylation as a function of biological complexity via dinucleotide inter-distances

We perform a statistical study of the distances between successive occurrencies of a given dinucleotide in the DNA sequence for a number of organisms of different complexity. Our analysis highlights peculiar features of the dinucleotide CG distribution in mammalian DNA, pointing towards a connection with the role of such dinucleotide in DNA methylation. While the CG distributions of mammals exhibit exponential tails with comparable parameters, the picture for the other organisms studied (e.g., fish, insects, bacteria and viruses) is more heterogeneous, possibly because in these organisms DNA methylation has different functional roles. Our analysis suggests that the distribution of the distances between dinucleotides CG provides useful insights in characterizing and classifying organisms in terms of methylation functionalities.Comment: 13 pages, 5 figures. To be published in the Philosophical Transactions A theme issue "DNA as information

New models of Parkinson’s like neuroinflammation in human microglia clone 3: Activation profiles induced by INF-γ plus high glucose and mitochondrial inhibitors

Microglia activation and neuroinflammation have been extensively studied in murine models of neurodegenerative diseases; however, to overcome the genetic differences between species, a human cell model of microglia able to recapitulate the activation profiles described in patients is needed. Here we developed human models of Parkinson’s like neuroinflammation by using the human microglia clone 3 (HMC3) cells, whose activation profile in response to classic inflammatory stimuli has been controversial and reported only at mRNA levels so far. In fact, we showed the increased expression of the pro-inflammatory markers iNOS, Caspase 1, IL-1β, in response to IFN-γ plus high glucose, a non-specific disease stimulus that emphasized the dynamic polarization and heterogenicity of the microglial population. More specifically, we demonstrated the polarization of HMC3 cells through the upregulation of iNOS expression and nitrite production in response to the Parkinson’s like stimuli, 6-hydroxidopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the latter depending on the NF-κB pathway. Furthermore, we identified inflammatory mediators that promote the pro-inflammatory activation of human microglia as function of different pathways that can simulate the phenotypic transition according to the stage of the pathology. In conclusion, we established and characterized different systems of HMC3 cells activation as in vitro models of Parkinson’s like neuroinflammation

Liposomes as a potential ocular delivery system of distamycin A

Liposomes containing Distamycin A (DA) may be clinically useful in the treatment of ocular HSV infections, especially in acyclovir-resistant HSV keratitis. This study evaluated the in vitro and in vivo performance of a topical controlled release liposomal formulation containing DA (DA-Lipo) aimed at reducing the toxicity of the encapsulated active agent and improving drug uptake by ocular tissues. The bioavailability of DA in the tear fluid and the DA uptake into the cornea were increased after instillation of DA-Lipo in rabbits, reaching the DA corneal concentration corresponding to IC50 values against HSV without any sign of transcorneal permeation of drug. DA-Lipo was definitely less cytotoxic then plain DA in rabbit corneal epithelial cells. These results provide new insights into the correlation between the in vitro data and the drug kinetics following ocular applications of liposomal vesicle

Camelina, an ancient oilseed crop actively contributing to the rural renaissance in Europe. A review

Promoting crop diversification in European agriculture is a key pillar of the agroecological transition. Diversifying crops generally enhances crop productivity, quality, soil health and fertility, and resilience to pests and diseases and reduces environmental stresses. Moreover, crop diversification provides an alternative means of enhancing farmers' income. Camelina (Camelina sativa (L.) Crantz) reemerged in the background of European agriculture approximately three decades ago, when the first studies on this ancient native oilseed species were published. Since then, a considerable number of studies on this species has been carried out in Europe. The main interest in camelina is related to its (1) broad environmental adaptability, (2) low-input requirements, (3) resistance to multiple pests and diseases, and (4) multiple uses in food, feed, and biobased applications. The present article is a comprehensive and critical review of research carried out in Europe (compared with the rest of the world) on camelina in the last three decades, including genetics and breeding, agronomy and cropping systems, and end-uses, with the aim of making camelina an attractive new candidate crop for European farming systems. Furthermore, a critical evaluation of what is still missing to scale camelina up from a promising oilseed to a commonly cultivated crop in Europe is also provided (1) to motivate scientists to promote their studies and (2) to show farmers and end-users the real potential of this interesting species