Prime osservazioni su specie perenni ed annue autoriseminanti in vista della organizzazione di catene di foraggiamento in ambienti mediterranei

Nel corso del periodo 1987-89 sono state valutate le potenzialità produttive e la distribuzione della produzione di 32 tra ecotipi e varietà di graminacee e leguminose foraggere annue e perenni provenienti prevalentemente dall'Italia centrale. La prova è stata condotta contemporaneamente in tre ambienti appartenenti a diverse zone bioclimatiche dell'area mediterranea (Perugia, Grosseto e Sassari) utilizzando uno schema sperimentale a blocchi randomizzati con quattro ripetizioni. I rilievi effettuati hanno riguardato il ricopri mento specifico e la produzione di sostanza secca determinata con criteri differenti: mensilmente per le leguminose annue; al 50% della fioritura e quindi mensilmente per le leguminose perenni; all'inizio della spigatura e quindi mensilmente per le graminacee. Per le specie annuali oltre alla sostanza secca è stata determinata la produzione di seme. L'obiettivo è stato quello di caratterizzare materiali che possano essere impiegati scalarmente per dilatare il periodo di utilizzazione diretta al pascolo. Dai risultati è stato possibile individuare, a seconda delle località, alcune popolazione di Medicago polymorpha L., Trifolium subterraneum L. e Lotus sp. pl. che hanno permesso di anticipare il periodo di utilizzazione primaverile e prolungare quello autunnale. Su questa base sono stati ipotizzati esempi di catene di foraggiamento semplificate (a tre anelli). Per quanto concerne le specie annue autoriseminanti, esse sembrano poter svolgere un importante ruolo nella regolazione della distribuzione stagionale della produzione foraggera nelle due località caratterizzate da un clima più tipicamente mediterraneo (Grosseto e Sassari) mentre la produzione di seme è risultata più che soddisfacente per assicurare l'autorisemina in tutte e tre le località. During the period 1987-1989, the yield and the distribution of forage production of 32 ecotypes and varieties of annual and perennial forage Iegumes and grasses were evaluated. The origin of plant materials was CentraI Italy. The trial was carried out in three environments characterized by different Mediterranean subclimates (Perugia, Grosseto and Sassari). The experimental design was a randomized complete block with four replicates. Specific ground cover was assessed in fall 1987, 1988 and 1989. Dry matter yield was assessed: monthly for annual legumes; at 50% of flowering and then monthly for perennial legumes; at early heading and then monthly for grasses. Seed yield of annual species was also recorded. Aim of the trial was to characterize plant materials that could be utilized subsequently in order to extend the period of direct utilization of herbage by grazing animals. It was possible depending on localities, to identify some populations of Medicago polymorpha L., Trifolium subterraneum L. and Lotus sp. pl.. that allowed to bring forward the spring utilization and to extend the autumn utilization. On the basis of the resu1ts obtained, it was possible to set up some simplified forage chains. Annual self reseeding species seemed to be more important to improve seasonal distribution of herbages in the typical Mediterranean locations (Sassari and Grosseto). Seed production was more than appreciable in order to allow self reseeding at the three locations

Interplay Between Age and Neuroinflammation in Multiple Sclerosis: Effects on Motor and Cognitive Functions

Aging is one of the main risk factors for the development of many neurodegenerative diseases. Emerging evidence has acknowledged neuroinflammation as potential trigger of the functional changes occurring during normal and pathological aging. Two main determinants have been recognized to cogently contribute to neuroinflammation in the aging brain, i.e., the systemic chronic low-grade inflammation and the decline in the regulation of adaptive and innate immune systems (immunosenescence, ISC). The persistence of the inflammatory status in the brain in turn may cause synaptopathy and synaptic plasticity impairments that underlie both motor and cognitive dysfunctions. Interestingly, such inflammation-dependent synaptic dysfunctions have been recently involved in the pathophysiology of multiple sclerosis (MS). MS is an autoimmune neurodegenerative disease, typically affecting young adults that cause an early and progressive deterioration of both cognitive and motor functions. Of note, recent controlled studies have clearly shown that age at onset modifies prognosis and exerts a significant effect on presenting phenotype, suggesting that aging is a significant factor associated to the clinical course of MS. Moreover, some lines of evidence point to the different impact of age on motor disability and cognitive deficits, being the former most affected than the latter. The precise contribution of aging-related factors to MS neurological disability and the underlying molecular and cellular mechanisms are still unclear. In the present review article, we first emphasize the importance of the neuroinflammatory dependent mechanisms, such as synaptopathy and synaptic plasticity impairments, suggesting their potential exacerbation or acceleration with advancing age in the MS disease. Lastly, we provide an overview of clinical and experimental studies highlighting the different impact of age on motor disability and cognitive decline in MS, raising challenging questions on the putative age-related mechanisms involved

Produzione di seme di leguminose foraggere annuali in tre ambienti italiani

The seed production of 18 natural populations and varieties of annual forage legumes mainly collected in CentraI Italy have been evaluated in three Italian sites with contrasting climate and soil types. AlI species belonged to the genus Medicago and Trifolium. The experiments were carried out in Perugia, Grosseto and Sassari that belong to different bioclimatic zones of the Mediterranean area. The folIowing measurements were taken: seedlings establishment, monthly covering rate, seed yield and its components, percentage of hard seeds. The medics seed yields were not uniform between years particular1y in Perugia where the highest average yield was reached (800 kg ha-1) while the lowest one was recorded in Sassari (300 kg ha-1). A subclover seed yield of about 1600 kg ha-1 was recorded in Perugia in the first year. The persian clover was the highest yielding among the clovers with small seed size (1000-1600 kg ha-1). The seed yield components showed that the seed yield and the number of legumes per square meter were not always correlated. Seed hardiness increased going from humid to semiarid environments. The results show a good potential for annual legume seed yield in the Mediterranean environment. This is important either for the persistency by self reseeding of species to be included permanently in pasturelands and also for the seed production at a commercial level. Moreover, results point out that by exploring Italian genetic resources it is possible to find interesting genotypes to be inc1uded in a wide range of agricultural environments. In tre ambienti italiani con caratteristiche pedo-climatiche differenti sono state valutate le potenzialità produttive di seme di 18 popolazioni e varietà di leguminose foraggere annuali, appartenenti ai generi Medicago e Trifolium, provenienti in prevalenza dal Centro-Italia. La prova è stata condotta-contemporaneamente in tre località corrispondenti ad altrettante zone bioclimatiche dell'area mediterranea (Perugia, Grosseto e Sassari). I rilievi effettuati hanno riguardato l'insediamento, il ricoprimento specifico mensile, la produzione di seme e le sue componenti e la percentuale di semi duri. Le produzioni di seme delle mediche sono risultate oscillanti negli anni, avendo raggiunto al primo e al terzo anno valori più elevati che al secondo, in particolar modo a Perugia dove sono state ottenute le produzioni medie più elevate (800 kg ha-1) mentre le più basse sono state registrate a Sassari (300 kg ha-1). La produzione di seme di trifoglio sotterraneo ha raggiunto valori considerevoli a Perugia al primo anno (circa 1600 kg ha-1). Per quanto riguarda i trifogli a seme minuto, il trifoglio persiano ha manifestato un elevato potenziale produttivo al primo anno nei tre ambienti di prova (1000-1600 kg ha-1). Riguardo le componenti della produzione i risultati ottenuti hanno mostrato che non sempre esiste uno stretto legame fra produzione di seme e numero di infruttescenze per unità di superficie. La durezza dei semi è risultata via via crescente dall'ambiente umido a quello semi-arido e mediamente inferiore nel trifoglio sotterraneo rispetto alle mediche ed ai trifogli a seme minuto. I risultati ottenuti hanno evidenziato in generale buone potenzialità per la produzione di seme di leguminose annuali in ambiente mediterraneo. Questo aspetto riveste un'importanza duplice: per la persistenza per autorisemina di specie da inserire permanentemente nella flora dei pascoli, e per la produzione di seme su scala commerciale. Inoltre, i risultati indicano che dall'esplorazione delle risorse genetiche italiane è possibile individuare genotipi particolarmente interessanti per l'inserimento in un'ampia gamma di realtà agricole e ambientali

Transient Receptor Potential Vanilloid 1 Modulates Central Inflammation in Multiple Sclerosis

Introduction: Disease course of multiple sclerosis (MS) is negatively influenced by proinflammatory molecules released by activated T and B lymphocytes and local immune cells. The endovanilloid system plays different physiological functions, and preclinical data suggest that transient receptor potential vanilloid type 1 (TRPV1) could modulate neuroinflammation in this disorder.Methods: The effect of TRPV1 activation on the release of two main proinflammatory cytokines, tumor necrosis factor (TNF) and interleukin (IL)-6, was explored in activated microglial cells. Furthermore, in a group of 132 MS patients, the association between the cerebrospinal fluid (CSF) levels of TNF and IL-6 and a single nucleotide polymorphisms (SNP) influencing TRPV1 protein expression and function (rs222747) was assessed.Results: In in vitro experiments, TRPV1 stimulation by capsaicin significantly reduced TNF and IL-6 release by activated microglial cells. Moreover, the anti-inflammatory effect of TRPV1 activation was confirmed by another TRPV1 agonist, the resiniferatoxin (RTX), whose effects were significantly inhibited by the TRPV1 antagonist, 5-iodoresiniferatoxin (5-IRTX). Vice versa, BV2 pre-treatment with 5-IRTX increased the inflammatory response induced by LPS. Moreover, in MS patients, a significant association emerged between TRPV1 SNP rs222747 and CSF TNF levels. In particular, the presence of a G allele, known to result in increased TRPV1 protein expression and function, was associated to lower CSF levels of TNF.Conclusions: Our results indicate that TRPV1 influences central inflammation in MS by regulating cytokine release by activated microglial cells. The modulation of the endovanilloid system may represent a useful approach to contrast neuroinflammation in MS

Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis

Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE

Laquinimod ameliorates excitotoxic damage by regulating glutamate re-uptake

Abstract Background Laquinimod is an immunomodulatory drug under clinical investigation for the treatment of the progressive form of multiple sclerosis (MS) with both anti-inflammatory and neuroprotective effects. Excitotoxicity, a prominent pathophysiological feature of MS and of its animal model, experimental autoimmune encephalomyelitis (EAE), involves glutamate transporter (GluT) dysfunction in glial cells. The aim of this study was to assess whether laquinimod might exert direct neuroprotective effects by interfering with the mechanisms of excitotoxicity linked to GluT function impairments in EAE. Methods Osmotic minipumps allowing continuous intracerebroventricular (icv) infusion of laquinimod for 4 weeks were implanted into C57BL/6 mice before EAE induction. EAE cerebella were taken to perform western blot and qPCR experiments. For ex vivo experiments, EAE cerebellar slices were incubated with laquinimod before performing electrophysiology, western blot, and qPCR. Results In vivo treatment with laquinimod attenuated EAE clinical score at the peak of the disease, without remarkable effects on inflammatory markers. In vitro application of laquinimod to EAE cerebellar slices prevented EAE-linked glutamatergic alterations without mitigating astrogliosis and inflammation. Moreover, such treatment induced an increase of Slcla3 mRNA coding for the glial glutamate–aspartate transporter (GLAST) without affecting the protein content. Concomitantly, laquinimod significantly increased the levels of the glial glutamate transporter 1 (GLT-1) protein and pharmacological blockade of GLT-1 function fully abolished laquinimod anti-excitotoxic effect. Conclusions Overall, our results suggest that laquinimod protects against glutamate excitotoxicity of the cerebellum of EAE mice by bursting the expression of glial glutamate transporters, independently of its anti-inflammatory effects

EFFECTS OF SIPONIMOD (BAF312) ON SYNAPTIC NEURODEGENERATIVE DAMAGE IN EXPERIMENTAL MULTIPLE SCLEROSIS

Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission, and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the CNS of mice with chronic progressive EAE. Minipumps allowing continuous intracerebroventricular (icv) infusion of siponimod for four weeks were implanted into C57BL/6 mice subjected to MOG35-55-induced EAE. Electrophysiology, immunohistochemistry, western blot, q-PCR experiments and peripheral lymphocyte counts were performed. In addition, the effect of siponimod on activated microglia was assessed in vitro to confirm the direct effect of the drug on CNS resident immune cells. Siponimod administration (0.45 g/day) induced a significant beneficial effect on EAE clinical scores with minimal effect on peripheral lymphocyte counts. Siponimod rescued defective GABAergic transmission in the striatum of EAE, without correcting the EAE-induced alterations of glutamatergic transmission. We observed a significant attenuation of astrogliosis and microgliosis together with reduced lymphocyte infiltration in the striatum of EAE mice treated with siponimod. Interestingly siponimod reduced the release of IL-6 and RANTES from activated microglial cells in vitro, which might explain the reduced lymphocyte infiltration. Furthermore, the loss of parvalbumin positive (PV+) GABAergic interneurons typical of EAE brains was rescued by siponimod treatment, providing a plausible explanation of the selective effects of this drug on inhibitory synaptic transmission. Altogether, our results show that siponimod has direct neuroprotective effects in the CNS of EAE mice, which are likely independent of its peripheral immune effect, suggesting that this drug could be effective in limiting neurodegenerative pathological processes in MS

Interplay Between Age and Neuroinflammation in Multiple Sclerosis: Effects on Motor and Cognitive Functions

Aging is one of the main risk factors for the development of many neurodegenerative diseases. Emerging evidence has acknowledged neuroinflammation as potential trigger of the functional changes occurring during normal and pathological aging. Two main determinants have been recognized to cogently contribute to neuroinflammation in the aging brain, i.e., the systemic chronic low-grade inflammation and the decline in the regulation of adaptive and innate immune systems (immunosenescence, ISC). The persistence of the inflammatory status in the brain in turn may cause synaptopathy and synaptic plasticity impairments that underlie both motor and cognitive dysfunctions. Interestingly, such inflammation-dependent synaptic dysfunctions have been recently involved in the pathophysiology of multiple sclerosis (MS). MS is an autoimmune neurodegenerative disease, typically affecting young adults that cause an early and progressive deterioration of both cognitive and motor functions. Of note, recent controlled studies have clearly shown that age at onset modifies prognosis and exerts a significant effect on presenting phenotype, suggesting that aging is a significant factor associated to the clinical course of MS. Moreover, some lines of evidence point to the different impact of age on motor disability and cognitive deficits, being the former most affected than the latter. The precise contribution of aging-related factors to MS neurological disability and the underlying molecular and cellular mechanisms are still unclear. In the present review article, we first emphasize the importance of the neuroinflammatory dependent mechanisms, such as synaptopathy and synaptic plasticity impairments, suggesting their potential exacerbation or acceleration with advancing age in the MS disease. Lastly, we provide an overview of clinical and experimental studies highlighting the different impact of age on motor disability and cognitive decline in MS, raising challenging questions on the putative age-related mechanisms involved