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In the Mediterranean Sea, where bottom trawling for demersal species is the most important fishery in terms of landings, around 75% of the assessed fish stocks are overfished. Its status as one of the world’s most heavily exploited seas and the one subject to the highest trawling pressure has become a global concern. An extensive review of bottom trawl selectivity studies was performed to assess the sustainability of this fishery in the Mediterranean; the selectivity parameters were collected from 93 peer-reviewed publications of 10 countries, totalling 742 records and 65 species. The review highlighted that i) the catch of bottom trawls commonly employed in the Mediterranean, even complying with current regulations on codend meshes, still includes immature individuals for 64-68% of the species investigated, and individuals under the minimum conservation reference size (MCRS) for 78% of the species investigated, and that ii) the MCRS set for 59% of the species analyzed is well below their length at first maturity, and is therefore ecologically inadequate. Although square-mesh codends are slightly more selective, the models developed herein demonstrate that improving size and species selectivity would require considerably larger meshes, which may significantly reduce profitability. The urgent need to reduce the biological impacts of bottom trawling in the Mediterranean should be addressed by promoting the adoption of more ecologically sustainable fishing gears through the introduction of more selective meshes or gear modifications.

Stock overexploitation, bycatch, discards and gear impacts on the environment are outstanding issues for Mediterranean fisheries. The adoption of alternative fishing gears is an appealing solution to ensure a more sustainable exploitation of resources. We discuss the pros and cons of pots as alternative gears by reviewing their main designs, spatial distribution and target species in the Mediterranean basin. We assessed the technical factors affecting the catch efficiency of the different pot designs for four target species: spiny lobster, Palinurus elephas; Norway lobster, Nephrops norvegicus; common octopus, Octopus vulgaris and pandalid shrimps, Plesionika spp. We found that pot volume is important to catch Octopus; mesh size to catch Nephrops and Plesionika; entrance surface to catch Octopus, Nephrops and Plesionika; pot shape/colour and entrance shape/position to catch Octopus and Plesionika; and bait type to catch Octopus and Nephrops. The literature review shows that pot fisheries have several considerable advantages over conventional gears, especially in terms of discards, bycatch, seabed impacts (particularly compared with bottom trawls and passive set nets), size and species selectivity, gear depredation, catch quality and gear cost, besides saving time and labour. Disadvantages hampering their wider diffusion include ghost fishing, a low catch of finfish species, the narrow range of species targeted by each pot design and the current early stage of research. These data make a clear case for using pots as alternative gears to traditional ones in the Mediterranean Sea in some areas and seasons to catch certain target species.

Age and growth studies provide critical data for clam fishery management. Three aging techniques, thin sections and acetate peel replicas – which involve shell sectioning – and surface growth rings were used to estimate the age and growth of Chamelea gallina populations in the mid-western Adriatic Sea. Their results were compared to identify the most reliable and least time-consuming approach. There were no significant differences between the two shell sectioning techniques (χ2 = 4.66, df = 3, p = 0.198), which were described by the same von Bertalanffy (VBF) growth curve parameters (L8 = 43.9, k = 0.26, t0 = −0.84), whereas significantly different L8 and k values were found between the two shell sectioning techniques and surface growth rings (L8: χ2 = 13.62, df = 1, p < 0.001; k: χ2 = 9.18, df = 1, p < 0.002; these statistics refer to the comparison between acetate peels and surface growth rings). The latter approach proved unreliable and error-prone, as it underestimated age and overestimated the growth rate (L8 = 26.4, k = 1.91, t0 = −0.11). Although the thin sections and acetate peel techniques both provide reliable age and growth estimates, the former approach was less time-consuming. Our analyses demonstrated that shell growth is slower in the cold season and in older specimens and that it has slowed down over the past few decades.

Aspartate-Glutamate Carrier 1 (AGC1) deficiency is a rare neurological disease caused by mutations in the solute carrier family 25, member 12 (SLC25A12) gene, encoding for the mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), a component of the malate&ndash, aspartate NADH shuttle (MAS), expressed in excitable tissues only. AGC1 deficiency patients are children showing severe hypotonia, arrested psychomotor development, seizures and global hypomyelination. While the effect of AGC1 deficiency in neurons and neuronal function has been deeply studied, little is known about oligodendrocytes and their precursors, the brain cells involved in myelination. Here we studied the effect of AGC1 down-regulation on oligodendrocyte precursor cells (OPCs), using both in vitro and in vivo mouse disease models. In the cell model, we showed that a reduced expression of AGC1 induces a deficit of OPC proliferation leading to their spontaneous and precocious differentiation into oligodendrocytes. Interestingly, this effect seems to be related to a dysregulation in the expression of trophic factors and receptors involved in OPC proliferation/differentiation, such as Platelet-Derived Growth Factor &alpha, (PDGF&alpha, ) and Transforming Growth Factor &beta, s (TGF&beta, s). We also confirmed the OPC reduction in vivo in AGC1-deficent mice, as well as a proliferation deficit in neurospheres from the Subventricular Zone (SVZ) of these animals, thus indicating that AGC1 reduction could affect the proliferation of different brain precursor cells. These data clearly show that AGC1 impairment alters myelination not only by acting on N-acetyl-aspartate production in neurons but also on OPC proliferation and suggest new potential therapeutic targets for the treatment of AGC1 deficiency.

none 13 no Available online 20 October 2017 Purine nucleoside phosphorylase (PNP), a crucial enzyme in purine metabolism which converts ribonucleosides into purine bases, has mainly been found inside glial cells. Since we recently demonstrated that PNP is released from rat C6 glioma cells, we then wondered whether this occurs in normal brain cells. Using rat primary cultures of microglia, astrocytes and cerebellar granule neurons, we found that in basal condition all these cells constitutively released a metabolically active PNP with Km values very similar to those measured in C6 glioma cells. However, the enzyme expression/release was greater in microglia or astrocytes that in neurons. Moreover, we exposed primary brain cell cultures to pro-inflammatory agents such as lipopolysaccharide (LPS) or ATP alone or in combination. LPS alone caused an increased interleukin-1β (IL-1β) secretion mainly from microglia and no modification in the PNP release, even from neurons in which it enhanced cell death. In contrast, ATP administered alone to glial cells at high micromolar concentrations significantly stimulated the release of PNP within 1 h, an effect not modified by LPS presence, whereas IL-1β secretion was stimulated by ATP only in cells primed for 2 h with LPS. In both cases ATP effect was mediated by P2X7 receptor (P2X7R), since it was mimicked by cell exposure to Bz-ATP, an agonist of P2X7R, and blocked by cell pre-treatment with the P2X7R antagonist A438079. Interestingly, ATP-induced PNP release from glial cells partly occurred through the secretion of lysosomal vesicles in the extracellular medium. Thus, during inflammatory cerebral events PNP secretion promoted by extracellular ATP accumulation might concur to control extracellular purine signals. Further studies could elucidate whether, in these conditions, a consensual activity of enzymes downstream of PNP in the purine metabolic cascade avoids accumulation of extracellular purine bases that might concur to brain injury by unusual formation of reactive oxygen species. mixed Peña-Altamira LE, Polazzi E, Giuliani P, Beraudi A, Massenzio F, Mengoni I, Poli A, Zuccarini M, Ciccarelli R, Di Iorio P, Virgili M, Monti B, Caciagli F. Peña-Altamira LE, Polazzi E, Giuliani P, Beraudi A, Massenzio F, Mengoni I, Poli A, Zuccarini M, Ciccarelli R, Di Iorio P, Virgili M, Monti B, Caciagli F.

The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) catalyzes a Ca2+-stimulated export of aspartate to the cytosol in exchange for glutamate, and is a key component of the malate-aspartate shuttle which transfers NADH reducing equivalents from the cytosol to mitochondria. By sustaining the complete glucose oxidation, AGC1 is thought to be important in providing energy for cells, in particular in the CNS and muscle where this protein is mainly expressed. Defects in the AGC1 gene cause AGC1 deficiency, an infantile encephalopathy with delayed myelination and reduced brain N-acetylaspartate (NAA) levels, the precursor of myelin synthesis in the CNS. Here, we show that undifferentiated Neuro2A cells with down-regulated AGC1 display a significant proliferation deficit associated with reduced mitochondrial respiration, and are unable to synthesize NAA properly. In the presence of high glutamine oxidation, cells with reduced AGC1 restore cell proliferation, although oxidative stress increases and NAA synthesis deficit persists. Our data suggest that the cellular energetic deficit due to AGC1 impairment is associated with inappropriate aspartate levels to support neuronal proliferation when glutamine is not used as metabolic substrate, and we propose that delayed myelination in AGC1 deficiency patients could be attributable, at least in part, to neuronal loss combined with lack of NAA synthesis occurring during the nervous system development.

Intracellular purine turnover is mainly oriented to preserving the level of triphosphate nucleotides, fundamental molecules in vital cell functions that, when released outside cells, act as receptor signals. Conversely, high levels of purine bases and uric acid are found in the extracellular milieu, even in resting conditions. These compounds could derive from nucleosides/bases that, having escaped to cell reuptake, are metabolized by extracellular enzymes similar to the cytosolic ones. Focusing on purine nucleoside phosphorylase (PNP) that catalyzes the reversible phosphorolysis of purine (deoxy)-nucleosides/bases, we found that it is constitutively released from cultured rat C6 glioma cells into the medium, and has a molecular weight and enzyme activity similar to the cytosolic enzyme. Cell exposure to 10 μM ATP or GTP increased the extracellular amount of all corresponding purines without modifying the levels/activity of released PNP, whereas selective activation of ATP P2Y1 or adenosine A2A metabotropic receptors increased PNP release and purine base formation. The reduction to 1% in oxygen supply (2 h) to cells decreased the levels of released PNP, leading to an increased presence of extracellular nucleosides and to a reduced formation of xanthine and uric acid. Conversely, 2 hour-cell re-oxygenation enhanced the extracellular amounts of both PNP and purine bases. Thus, hypoxia and re-oxygenation modulated in opposite manner the PNP release/activity and, thereby, the extracellular formation of purine metabolism end-products. In conclusion, extracellular PNP and likely other enzymes deputed to purine base metabolism are released from cells, contributing to the purinergic system homeostasis and exhibiting an important pathophysiological role. This article is protected by copyright. All rights reserved.

Apolipoprotein E (ApoE) is mainly secreted by glial cells and is involved in many brain functions, including neuronal plasticity, β-amyloid clearance, and neuroprotection. Microglia--the main immune cells of the brain--are one source of ApoE, but little is known about the physiologic regulation of microglial ApoE secretion by neurons and whether this release changes under inflammatory or neurodegenerative conditions. Using rat primary neural cell cultures, we show that microglia release ApoE through a Golgi-mediated secretion pathway and that ApoE progressively accumulates in neuroprotective microglia-conditioned medium. This constitutive ApoE release is negatively affected by microglial activation both with lipopolysaccharide and with ATP. Microglial ApoE release is stimulated by neuron-conditioned media and under coculture conditions. Neuron-stimulated microglial ApoE release is mediated by serine and glutamate through N-methyl-D-aspartate receptors and is differently regulated by activation states (i.e. lipopolysaccharide vs ATP) and by 6-hydroxydopamine. Microglial ApoE silencing abrogated protection of cerebellar granule neurons against 6-hydroxydopamine toxicity in cocultures, indicating that microglial ApoE release is neuroprotective. Our findings shed light on the reciprocal cross-talk between neurons and microglia that is crucial for normal brain functions. They also open the way for the identification of possible pharmacologic targets that can modulate neuroprotective microglial ApoE release under pathologic conditions.

Natural polyamines (putrescine, spermidine and spermine) are ubiquitous molecules known to regulate a number of physiological processes and suspected to play a role also in various pathological conditions. Changes in polyamine levels and in their biosynthetic enzymes have been described for some neurodegenerative diseases but the available data are incomplete and somewhat contradictory. We report here alterations of the key enzyme of the polyamine pathway, ornithine decarboxylase (ODC) catalytic activity and polyamine levels in different CNS areas from SOD1 G39A transgenic mice, an animal model for amyotrophic lateral sclerosis (ALS). ODC catalytic activity, was found significantly increased both in the cervical and lumbar spinal cord and, to a lesser extent in the brain stem of transgenic mice at a symptomatic stage of the disease (125 day-old mice), while no differences were present at a pre-symptomatic stage (55 day-old mice). In parallel with the increase of ODC activity putrescine levels were several times increased in both cervical and lumbar spinal cord and in the brain stem of 125 day-old SOD1 G39A mice. Higher order polyamines were not increased except for a significant increase of spermidine in the cervical spinal cord. The present data demonstrate considerable alterations of the ODC/polyamine system in a reliable animal model of ASL, consistent with their role in neurodegeneration and in particular in motor neuron diseases.

Dietary supplementation with creatine has proven to be beneficial in models of acute and chronic neurodegeneration. We report here data on the neurochemical correlates of differential protection of long-term creatine supplementation in two models of excitotoxicity in rats, as well as in the mouse model for ALS (G93A mice). In rats, the fall in cholinergic and GABAergic markers due to the excitotoxic death of intrinsic neurons caused by intrastriatal infusion of the neurotoxin, ibotenic acid, was significantly prevented by long-term dietary supplementation with creatine. On the contrary, creatine was unable to recover a cholinergic marker in the cortex of rats subjected to the excitotoxic death of the cholinergic basal forebrain neurons. In G93A mice, long-term creatine supplementation marginally but significantly increased mean lifespan, as previously observed by others, and reverted the cholinergic deficit present in some forebrain areas at an intermediate stage of the disease. In both rats and mice, creatine supplementation increased the activity of the GABAergic enzyme, glutamate decarboxylase, in the striatum but not in other brain regions. The present data point at alterations of neurochemical parameters marking specific neuronal populations, as a useful way to evaluate neuroprotective effects of long-term creatine supplementation in animal models of neurodegeneration.

Transgenic mice carrying the human mutated SOD1 gene with a glycine/alanine substitution at codon 93 (G93A) are a widely used model for the fatal human disease amyotrophic lateral sclerosis (ALS). In these transgenic mice, we carried out a neurochemical study not only restricted to the primarily affected regions, the cervical and lumbar segments of the spinal cord, but also to several other brain regions. At symptomatic (110 and 125 days of age), but not at pre-symptomatic (55 days of age) stages, we found significant decreases in catalytic activity of the cholinergic enzyme, choline acetyltransferase (ChAT) in the hippocampus, olfactory cortex and fronto-parietal cortex. In parallel, we observed a decreased number of basal forebrain cholinergic neurons projecting to these areas. No alterations of the cholinergic markers were noticed in the striatum and the cerebellum. A widespread marker for GABAergic neurons, glutamate decarboxylase (GAD), was unaffected in all the areas examined. Alteration of cholinergic markers in forebrain areas was paralleled by concomitant alterations in the spinal cord and brainstem, as a consequence of progressive apoptotic elimination of cholinergic motor neuron. Gestational supplementation of choline, while able to result in long-term enhancement of cholinergic activity, did not improve transgenic mice lifespan nor counteracted cholinergic impairment in brain regions and spinal cord.

Neurochemical alterations of markers related to synaptic function are potential candidates for age-related impairment of brain function and cognition. The process of aging, including brain aging, can be counteracted to some degree by maintaining animals in long-term conditions of caloric restriction, or supplementing their diet with antioxidant substances. We report here that the age-related decline of the cholinergic and GABAergic systems, that takes place in some CNS regions of aged rats, is not affected by maintaining them under conditions of dietary restriction and, therefore, of reduced calorie intake, from the 12th to the 30th month of age. We also notice the same lack of effect by adding, during the same period, the aging rat diet with the potential antioxidant substance, N-acetylcysteine (NAC). The same dietary manipulations are also unable to counteract the derangement of the first step of the main biosynthetic pathway for polyamines, putative neuromodulators in the CNS, that occurs in the aged spinal cord. Some age-related alterations in the expression of different subunits of the NMDA-type glutamate receptors in some CNS regions of aged rats were instead, at least in some cases, counteracted by long-term dietary manipulation.

Valproic acid (VPA), an established antiepileptic and antimanic drug, has recently emerged as a promising neuroprotective agent. Among its many cellular targets, VPA has been recently demonstrated to be an effective inhibitor of histone deacetylases. Accordingly, we have adopted a schedule of dietary administration (2% VPA added to the chow) that results in a significant inhibition of histone deacetylase activity and in an increase of histone H3 acetylation in brain tissues of 4 weeks-treated rats. We have tested this schedule of VPA treatment in an animal model of Parkinson's disease (PD), in which degeneration of nigro-striatal dopaminergic neurons is obtained through sub-chronic administration of the mitochondrial toxin, rotenone, via osmotic mini pumps implanted to rats. The decrease of the dopaminergic marker tyrosine hydroxylase in substantia nigra and striatum caused by 7 days toxin administration was prevented in VPA-fed rats. VPA treatment also significantly counteracted the death of nigral neurons and the 50% drop of striatal dopamine levels caused by rotenone administration. The PD-marker protein alpha-synuclein decreased, in its native form, in substantia nigra and striatum of rotenone-treated rats, while monoubiquitinated alpha-synuclein increased in the same regions. VPA treatment counteracted both these alpha-synuclein alterations. Furthermore, monoubiquitinated alpha-synuclein increased its localization in nuclei isolated from substantia nigra of rotenone-treated rats, an effect also prevented by VPA treatment. Nuclear localization of alpha-synuclein has been recently described in some models of PD and its neurodegenerative effect has been ascribed to histone acetylation inhibition. Thus, the ability of VPA to increase histone acetylation is a novel candidate mechanism for its neuroprotective action.