Pre-reproductive parental enriching experiences influence progeny’s developmental trajectories

While the positive effects of environmental enrichment (EE) applied after weaning, in adulthood, during aging, or even in the presence of brain damage have been widely described, the transgenerational effects of pre-reproductive EE have been less examined. And yet, this issue is remarkable given that parental environmental experience may imprint offspring's phenotype over generations through many epigenetic processes. Interactions between individual and environment take place lifelong even before conception. In fact, the environment pre-reproductively experienced by the mother and/or the father exerts a substantial impact on neural development and motor and cognitive performances of the offspring, even if not directly exposed to social, cognitive, physical and/or motor enrichment. Furthermore, pre-reproductive parental enrichment exerts a transgenerational impact on coping response to stress as well as on the social behavior of the offspring. Among the effects of pre-reproductive parental EE, a potentiation of the maternal care and a decrease in global methylation levels in the frontal cortex and hippocampus of the progeny have been described. Finally, pre-reproductive EE modifies different pathways of neuromodulation in the brain of the offspring (involving brain-derived neurotrophic factor, oxytocin and glucocorticoid receptors). The present review highlights the importance of pre-reproductive parental enrichment in altering the performances not only of animals directly experiencing it, but also of their progeny, thus opening the way to new hypotheses on the inheritance mechanisms of behavioral trait

Le indagini geochimiche come strumento di supporto ai piani di bonifica di siti minerari dismessi: la miniera di Abbadia San Salvatore (Monte Amiata, Siena)

La caratterizzazione ambientale di un sito è identificabile con l’insieme delle attività che permettono di ricostruire i fenomeni di contaminazione a carico delle matrici ambientali, in modo da ottenere le informazioni di base su cui prendere decisioni realizzabili e sostenibili per la messa in sicurezza e/o bonifica del sito. L’allegato 2 al Titolo V del D.L. 152/2006 riporta i criteri generali per la messa in sicurezza, la bonifica ed il ripristino ambientale dei siti inquinati, nonché per la redazione dei progetti di bonifica. Nella legislazione attuale, non sono però presenti dei protocolli tecnici standardizzati per l’elaborazione di modelli in grado di definire l’estensione dell’area contaminata, i volumi di suolo contaminato, per l’esecuzione del monitoraggio delle varie matrici ambientali, per l’individuazione delle specie chimiche responsabili dell’inquinamento. La predisposizione di un piano di indagini ambientali finalizzato alla definizione dello stato di inquinamento delle matrici ambientali stesse viene, in tal modo, completamente demandato al soggetto cui compete inoltre l’obbligo di eseguire gli interventi di messa in sicurezza e/o di bonifica del sito, sulla base dei progetti redatti. É in questo quadro che si colloca il presente lavoro di tesi che, attraverso l’applicazione di tecniche indirette di indagine, vuole sottolineare l’importanza delle stesse quali metodologie utili ai fini di una migliore caratterizzazione ambientale del sito oggetto di indagine. Questo lavoro, realizzato nel sito minerario di Abbadia San Salvatore ed in particolare nel “Lotto 6” di bonifica, che risulta essere quello maggiormente inquinato rispetto agli altri “lotti” individuati all’interno dell’area mineraria, ha previsto le seguenti attività: - Modellizzazione tridimensionale dell’area metallurgica; - Studio idrogeochimico delle acque; - Misura dei flussi di CO2 all’interfaccia suolo-aria. In tal modo, si vuole offrire da un lato un contributo alla conoscenza del sito minerario di Abbadia San Salvatore, dall’altro, produrre un approccio metodologico per la caratterizzazione ambientale della suddetta area, che potrebbe risultare d’interesse nell’ambito della bonifica attualmente in corso di svolgimento

Influence of pre-reproductive maternal enrichment on coping response to stress and expression of c-Fos and glucocorticoid receptors in adolescent offspring

Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of standard dams. These results highlight the profound influence of a stressful condition, such as the social isolation, on the brain of adolescent rats, and underline intergenerational effects of maternal experiences in regulating the offspring response to stress

Interaction does count: A cross-fostering study on transgenerational effects of pre-reproductive maternal enrichment

Pre-reproductive environmental enrichment of female rats influences sensorimotor development and spatial behavior of the offspring, possibly through the changed maternal nurturing. Nevertheless, maternal care could be not the solely responsible for changing offspring developmental trajectories. To disentangle the specific contribution to the transgenerational inheritance of pre- and post-natal factors, a cross-fostering study was performed. Female rats were reared in an enriched environment from weaning to sexual maturity, while control female rats were reared under standard conditions. Following mating with standard-reared males, all females were housed individually. Immediately after delivery, in- or cross-fostering manipulations were performed so that any foster dams received pups born to another dam of the same (in-fostering) or the opposite (cross-fostering) pre-reproductive rearing condition. In lactating dams maternal care and nesting activities were assessed, while in their male pups spatial abilities were assessed through Morris Water Maze (MWM) test at post-natal day 45. Moreover, the expression of Brain-Derived-Neurotrophic-Factor (BDNF) was evaluated in the hippocampus and frontal cortex of dams and pups at weaning. Pre-reproductive maternal environmental enrichment, followed by adoption procedures, loosened its potential in modifying maternal care and offspring developmental trajectories, as indicated by the lack of differences between in-fostered groups of dams and pups. In addition, enriched dams rearing standard pups showed the least complex maternal repertoire (the highest sniffing duration and the lowest nest quality), and their pups showed a reduced spatial learning in the MWM. Nevertheless, pre-reproductive maternal enrichment kept influencing neurotrophic pattern, with enriched dams expressing increased frontal BDNF levels (regardless of the kind of fostered pups), and their offspring expressing increased hippocampal BDNF levels. The present findings enlighten the crucial importance of the early mother-pups interactions in influencing maternal care and offspring phenotype, with the enriched dam-standard pups couple resulting in the most maladaptive encounter. Our study thus sustains that the bidirectional interactions between mother and pups are able to deeply shape offspring phenoty

Pre-reproductive Parental Enriching Experiences Influence Progeny’s Developmental Trajectories

While the positive effects of environmental enrichment (EE) applied after weaning, in adulthood, during aging, or even in the presence of brain damage have been widely described, the transgenerational effects of pre-reproductive EE have been less examined. And yet, this issue is remarkable given that parental environmental experience may imprint offspring’s phenotype over generations through many epigenetic processes. Interactions between individual and environment take place lifelong even before conception. In fact, the environment pre-reproductively experienced by the mother and/or the father exerts a substantial impact on neural development and motor and cognitive performances of the offspring, even if not directly exposed to social, cognitive, physical and/or motor enrichment. Furthermore, pre-reproductive parental enrichment exerts a transgenerational impact on coping response to stress as well as on the social behavior of the offspring. Among the effects of pre-reproductive parental EE, a potentiation of the maternal care and a decrease in global methylation levels in the frontal cortex and hippocampus of the progeny have been described. Finally, pre-reproductive EE modifies different pathways of neuromodulation in the brain of the offspring (involving brain-derived neurotrophic factor, oxytocin and glucocorticoid receptors). The present review highlights the importance of pre-reproductive parental enrichment in altering the performances not only of animals directly experiencing it, but also of their progeny, thus opening the way to new hypotheses on the inheritance mechanisms of behavioral traits

Targeting of PDGF-C/NRP-1 autocrine loop as a new strategy for counteracting the invasiveness of melanoma resistant to braf inhibitors

: Melanoma resistance to BRAF inhibitors (BRAFi) is often accompanied by a switch from a proliferative to an invasive phenotype. Therefore, the identification of signaling molecules involved in the development of metastatic properties by resistant melanoma cells is of primary importance. We have previously demonstrated that activation of neuropilin-1 (NRP-1) by platelet-derived growth factor (PDGF)-C confers melanoma cells with an invasive behavior similar to that of BRAFi resistant tumors. Aims of the present study were to evaluate the role of PDGF-C/NRP-1 autocrine loop in the acquisition of an invasive and BRAFi-resistant phenotype by melanoma cells and the effect of its inhibition on drug resistance and extracellular matrix (ECM) invasion. Furthermore, we investigated whether PDGF-C serum levels were differentially modulated by drug treatment in metastatic melanoma patients responsive or refractory to BRAFi as single agents or in combination with MEK inhibitors (MEKi). The results indicated that human melanoma cells resistant to BRAFi express higher levels of PDGF-C and NRP-1 as compared to their susceptible counterparts. Overexpression occurs early during development of drug resistance and contributes to the invasive properties of resistant cells. Accordingly, silencing of NRP-1 or PDGF-C reduces tumor cell invasiveness. Analysis of PDGF-C in the serum collected from patients treated with BRAFi or BRAFi+MEKi, showed that in responders PDGF-C levels decrease after treatment and raise again at tumor progression. Conversely, in non-responders treatment does not affect PDGF-C serum levels. Thus, blockade of NRP-1 activation by PDGF-C might represent a new therapeutic approach to counteract the invasiveness of BRAFi-resistant melanoma

MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women

To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI

Regressing Multiple Viral Plaques and Skin Fragility Syndrome in a Cat Coinfected with FcaPV2 and FcaPV3

Feline viral plaques are uncommon skin lesions clinically characterized by multiple, often pigmented, and slightly raised lesions. Numerous reports suggest that papillomaviruses (PVs) are involved in their development. Immunosuppressed and immunocompetent cats are both affected, the biological behavior is variable, and the regression is possible but rarely documented. Here we report a case of a FIV-positive cat with skin fragility syndrome and regressing multiple viral plaques in which the contemporary presence of two PV types (FcaPV2 and FcaPV3) was demonstrated by combining a quantitative molecular approach to histopathology. The cat, under glucocorticoid therapy for stomatitis and pruritus, developed skin fragility and numerous grouped slightly raised nonulcerated pigmented macules and plaques with histological features of epidermal thickness, mild dysplasia, and presence of koilocytes. Absolute quantification of the viral DNA copies (4555 copies/microliter of FcaPV2 and 8655 copies/microliter of FcaPV3) was obtained. Eighteen months after discontinuation of glucocorticoid therapy skin fragility and viral plaques had resolved. The role of the two viruses cannot be established and it remains undetermined how each of the viruses has contributed to the onset of VP; the spontaneous remission of skin lesions might have been induced by FIV status change over time due to glucocorticoid withdraw and by glucocorticoids withdraw itself

Case report: optic atrophy and nephropathy with m.13513G>A/MT-ND5 mtDNA pathogenic variant

Isolated complex I deficiency represents the most common mitochondrial respiratory chain defect involved in mitochondrial disorders. Among these, the mitochondrial DNA (mtDNA) m.13513G>A pathogenic variant in the NADH dehydrogenase 5 subunit gene (MT-ND5) has been associated with heterogenous manifestations, including phenotypic overlaps of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, Leigh syndrome, and Leber’s hereditary optic neuropathy (LHON). Interestingly, this specific mutation has been recently described in patients with adult-onset nephropathy. We, here, report the unique combination of LHON, nephropathy, sensorineural deafness, and subcortical and cerebellar atrophy in association with the m.13513G>A variant

第806回 千葉医学会・第10回 歯科口腔外科例会 20.

Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by defective intracellular trafficking of exogenous cholesterol. Purkinje cell (PC) degeneration is the main sign of cerebellar dysfunction in both NPC1 patients and animal models. It has been recently shown that a significant decrease in Sonic hedgehog (Shh) expression reduces the proliferative potential of granule neuron precursors in the developing cerebellum of Npc1 (-/-) mice. Pursuing the hypothesis that this developmental defect translates into functional impairments, we have assayed Npc1-deficient pups belonging to the milder mutant mouse strain Npc1 (nmf164) for sensorimotor development from postnatal day (PN) 3 to PN21. Npc1 (nmf164) / Npc1 (nmf164) pups displayed a 2.5-day delay in the acquisition of complex motor abilities compared to wild-type (wt) littermates, in agreement with the significant disorganization of cerebellar cortex cytoarchitecture observed between PN11 and PN15. Compared to wt, Npc1 (nmf164) homozygous mice exhibited a poorer morphological differentiation of Bergmann glia (BG), as indicated by thicker radial shafts and less elaborate reticular pattern of lateral processes. Also BG functional development was defective, as indicated by the significant reduction in GLAST and Glutamine synthetase expression. A reduced VGluT2 and GAD65 expression also indicated an overall derangement of the glutamatergic/GABAergic stimulation that PCs receive by climbing/parallel fibers and basket/stellate cells, respectively. Lastly, Npc1-deficiency also affected oligodendrocyte differentiation as indicated by the strong reduction of myelin basic protein. Two sequential 2-hydroxypropyl-β-cyclodextrin administrations at PN4 and PN7 counteract these defects, partially preventing functional impairment of BG and fully restoring the normal patterns of glutamatergic/GABAergic stimulation to PCs.These findings indicate that in Npc1 (nmf164) homozygous mice the derangement of synaptic connectivity and dysmyelination during cerebellar morphogenesis largely anticipate motor deficits that are typically observed during adulthood