1,720,983 research outputs found
Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats
No full text1 S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons is involved in the therapeutic mechanisms of antidepressants. 2 The effect of SAMe in an animal model of 'depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats. 3 Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg(-1) daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg(-1) daily i.p.) produced a similar effect after a 3 week treatment. 4 Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg(-1) daily i.m.)- and in imipramine (10 mg kg(-1) daily i.p.)-treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats. 5 Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test. 6 While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment. 7 These results show that SAMe reverses an experimental condition of 'depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects
Chemical Characterization and Beneficial Effects of Walnut Oil on a Drosophila melanogaster Model of Parkinson’s Disease
Get PDFA nutritional approach could be a promising strategy to prevent or decrease the progression of neurodegenerative disorders such as Parkinson’s disease (PD). The neuroprotective role of walnut oil (WO) was investigated in Drosophila melanogaster treated with rotenone (Rot), as a PD model, WO, or their combination, and compared to controls. WO reduced mortality and improved locomotor activity impairment after 3 and 7 days, induced by Rot. LC-MS analyses of fatty acid levels in Drosophila heads showed a significant increase in linolenic (ALA) and linoleic acid (LA) both in flies fed with the WO-enriched diet and in those treated with the association of WO with Rot. Flies supplemented with the WO diet showed an increase in brain dopamine (DA) level, while Rot treatment significantly depleted dopamine content; conversely, the association of Rot with WO did not modify DA content compared to controls. The greater intake of ALA and LA in the enriched diet enhanced their levels in Drosophila brain, suggesting a neuroprotective role of polyunsaturated fatty acids against Rot-induced neurotoxicity. The involvement of the dopaminergic system in the improvement of behavioral and biochemical parameters in Drosophila fed with WO is also suggested
Characterization of Walnut Oil and Evaluation of Its Neuroprotective Effects in an In Vitro Model of Parkinson’s Disease
No full textParkinson’s disease (PD) is a common neurodegenerative disorder marked by the degeneration of dopaminergic neurons and the buildup of α-synuclein aggregates. The current treatments focus on symptom relief, with no drugs available to halt disease progression. This has prompted interest in plant-based extracts as alternative therapies. This study examines the neuroprotective and antioxidant effects of walnut oil (WO), extracted from Juglans regia L., in an in vitro PD model using the neurotoxin rotenone (ROT). WO, rich in polyunsaturated fatty acids (PUFAs), including linoleic acid (LA) and α-linolenic acid (ALA), together with minor bioactive components, is known for its neuroprotective properties. Using human HMC3 microglial and SH-SY5Y neuroblastoma cells, we tested WO’s effects on ROT-induced toxicity. The experiments were performed at different time points. The results showed that the co-administration of WO with ROT significantly improved cell viability and reduced reactive oxygen species (ROS) levels. Additionally, conditioned media from WO-treated HMC3 cells enhanced SH-SY5Y cell survival, indicating positive microglia–neuron interactions. Cell viability appeared to be concentration- and time-dependent. These findings highlight WO’s potential, mainly due to its PUFA content, as a promising candidate for preventing neurodegenerative diseases like PD; they underscore the potential of WO content in food for the prevention of neurodegenerative diseases such as PD
In vitro characterization of the cytokine Drosophila Helical factor
No full textDrosophila Helical factor (Hf) is a protein discovered through the QT method, an algorithm specifically designed for finding helical cytokines. Since in vivo experiments suggested the involvement of Hf in Drosophila melanogaster immunity, we have proceeded with the characterization of Hf functions in the macrophage-like Drosophila embryonic hemocytes, SL2 cell line. qPCR results demonstrated that Hf gene is induced in the SL2 cell line, after either 6 or 24 h incubation with Escherichia coli-purified peptidoglycan. The silencing of Hf expression through RNAi resulted in the reduced capability of synthesizing antimicrobial peptides (AMP) after exposure to heat-inactivated E. coli. The effects of the recombinant peptide rHf have also been tested in the SL2 cell line. rHf promotes the expression and triggers the release of Hf from the hemocytes, and stimulates the synthesis of the antimicrobial peptides (AMP) Defensin and Drosomycin, without any further immune stimulation. Consistent with the output of the QT method, which predicts Hf as a secreted protein, chromatin immune-precipitation experiments confirmed that Hf does not bind DNA, excluding that it acts as an immune-regulated transcription factor. Finally, rHf neither exerts chemotactic action nor triggers bacterial phagocytosis in SL2 cells.Altogether, our data supports the prediction that Hf is an helical cytokine produced and secreted by the hemocytes and it is mainly involved in the regulation of the humoral component of the immune response of D. melanogaster
The antinociceptive effect of acetylsalicylic acid is differently affected by a CB1 agonist or antagonist and involves the serotonergic system in rats
No full textCombinations of non steroidal anti-inflammatory drugs (NSAIDs) and cannabinoids are promising because of their potential synergistic effects in analgesia, resulting in a reduction in dosage and minimizing adverse reactions. The analgesic effect of Acetylsalicylic acid (ASA), probably due to a central mechanism, also implicates changes in the central monoaminergic system. Therefore, we decided to evaluate the antinociceptive interaction between the CB1 receptor agonist, HU210, and ASA in tests involving central pain in rats as well as the implication of the central serotonergic system thereon
Pharmacological manipulation of brain galaninergic system and sexual behavior in male mice
No full textAvailable data suggest a complex role for the brain galaninergic system in male sexual behavior; however, the results so far obtained in animals with either galanin or galanin antagonists are conflicting. Objective: To define the better influence of galanin on male sexual behavior by studying, in mice, (i) the effect of galanin and of the chimeric galanin peptide M40 on the copulatory performance, and (ii) galanin mRNA levels in hypothalamic arcuate and dorso-medial nuclei. Methods: For the behavioral testing, only sexually sluggish male mice were used. Galanin mRNA levels were studied in both sexually potent and impotent mice by means of in situ hybridization. Standard behavioral parameters for sexual behavior were recorded or calculated. Synthetic galanin (0.05, 0.1 or 1 mug/mouse) and M40 (5 or 20 mug/mouse) were intracerebroventricularly (ICV) injected, 15 min before the copulatory test. Galanin mRNA levels were evaluated. Results: In sexually sluggish male mice, both galanin (0.1 and 1 mug/mouse ICV) and M40 (20 mug/mouse ICV), significantly increased intromission frequency and ejaculation latency; M40 also improved copulatory efficacy. On the other hand, in the hypothalamic arcuate and dorso-medial nuclei, the levels of galanin mRNA were not significantly different in sexually potent and impotent male mice. Conclusions.-These results show that in sexually sluggish male mice the ICV injection of either galanin or the chimeric analogue M40 greatly prolongs the duration of the copulation; without a reduction of the sexual drive or of the copulatory performance. On the other hand, the hybridization experiments seem to rule out an important physiological role of the brain galaninergic system in the regulation of male sexual behavior, at least in mice
Influence of f-MLP, ACTH(1-24) and CRH on in vitro chemotaxis of monocytes from centenarians
No full textOBJECTIVE: The lifelong exposure to a variety of stressors activates a plethora of defense mechanisms, including the hypothalamic-pituitary-adrenal axis which releases neuropeptides affecting the immune responses. Here, we report data on the capability of monocytes from young subjects and centenarians to migrate towards chemotactic stimuli (formyl-methionyl-leucyl-phenylalanine, f-MLP; adrenocorticotropic hormone, ACTH, and corticotrophin-releasing hormone, CRH). Plasma levels of ACTH, CRH and cortisol were measured as an index of ongoing stress response. METHODS: Monocyte chemotaxis towards f-MLP (10(-8)M), ACTH(1-24) (10(-14) and 10(-8)M) and CRH (10(-14) and 10(-8)M) was evaluated in vitro in young subjects (n = 8, age range 25-35 years) and centenarians (n = 9, age >100 years) and expressed as chemotactic index. In 9 young subjects and 6 centenarians, plasma levels of cortisol, ACTH and CRH were measured. RESULTS: Monocyte chemotaxis towards f-MLP, ACTH(1-24) and CRH (10(-8)M) was well preserved in centenarians, except when the lowest concentration of CRH was used. CRH, ACTH and cortisol plasma levels were significantly higher in centenarians than in young subjects. CONCLUSIONS: The capability of monocytes from centenarians to respond to chemotactic neuropeptides is well preserved. The decreased responsiveness to the lowest concentration of CRH might be due to downregulation of CRH receptors or to defects in the intracellular signal transduction pathway. The high plasma levels of cortisol, CRH and ACTH in centenarians indicate an activation of the entire stress axis, likely counteracting the systemic inflammatory process occurring with age. This activation fits with the hypothesis that lifelong low-intensity stressors activate ancient, hormetic defense mechanisms, favoring healthy aging and longevity
Beta-amyloid fibrillation and/or hyperhomocysteinemia modify striatal patterns of hyaluronic acid and dermatan sulfate: possible role in the pathogenesis of Alzheimer's disease.
No full textA key event in Alzheimer's disease (AD) pathogenesis is the formation of insoluble peptides -amyloid aggregates and this process is favoured by a condition of hyperhomocysteinemia. To date, there is growing evidence that implicates glycosaminoglycans (GAGs) in the pathophysiology of amyloidosis but no data are available on the characterization of brain GAGs involved in the enhancing -amyloid fibrillogenesis in relationship to their structure and physico-chemical properties. Furthermore, few studies have been performed on the relationship between hyperhomocysteinemia and extracellular matrix (ECM) modifications. The aim of this study was to evaluate the amount and chemical structure of GAGs in rat striatal areas where -amyioid fibrillogenesis was induced, and in conditions of hyperhomocysteinemia. The intrastriatal injection of -amyloid produced a significant decrease (-40.8%) in the hyaluronic acid (HA) percentage and an increase (+14.5%) in the dermatan sulfate (DS) with a total charge density increasing of 14.9%. A significant decrease (-19.5%) in the HA percentage and an increase (+6.9%) in the DS % was also observed in striata obtained from the hyperhomocysteinemic animals. The total charge density increased by 6.8%. Quite the same trend was observed in rats after intrastriatal injection of -amyloid and in a condition of hyperhomocysteinemia. The observed increase of DS concentration and the correspondent decrease of the nonsulfated polymer HA after in vivo treatment with -amyloid and in a condition of hyperhocysteinemia support the hypothesis that an increase in local production of sulfated GAGs may reduce -amyloid neurotoxicity. However, the consequent modification of the ECM network might impair the extracellular diffusion pathways of different signal molecules and participate in the progression of AD
Collagen VI regulates peripheral nerve regeneration by modulating macrophage recruitment and polarization
Get PDFMacrophages contribute to peripheral nerve regeneration and produce collagen VI, an extracellular matrix protein involved in nerve function. Here, we show that collagen VI is critical for macrophage migration and polarization during peripheral nerve regeneration. Nerve injury induces a robust upregulation of collagen VI, whereas lack of collagen VI in Col6a1(-/-) mice delays peripheral nerve regeneration. In vitro studies demonstrated that collagen VI promotes macrophage migration and polarization via AKT and PKA pathways. Col6a1(-/-) macrophages exhibit impaired migration abilities and reduced antiinflammatory (M2) phenotype polarization, but are prone to skewing toward the proinflammatory (M1) phenotype. In vivo, macrophage recruitment and M2 polarization are impaired in Col6a1(-/-) mice after nerve injury. The delayed nerve regeneration of Col6a1(-/-) mice is induced by macrophage deficits and rejuvenated by transplantation of wild-type bone marrow cells. These results identify collagen VI as a novel regulator for peripheral nerve regeneration by modulating macrophage function
[In vitro study of periodontal ligament cells].
No full textThe aim of this research is to outline a procedure able to promote specific cellular differentiation and proliferation with consequent periodontal regeneration. To achieve this goal, use was made of various compounds supposed to have the capacity of aiding periodontal regeneration.The cells utilised for this study were obtained from explants of human periodontal ligaments. Their proliferation and differentiation capacity was examined in the presence of: coral granules (350, 500 mu), collagene type 1, growth factors (Platelet derived growth factor, PDGF and Transforming growth factor beta 1, TGF beta 1), both on their own and in different combination with one another. The differentiation activity was evaluated by ultrastructural morphological method (Transmission electron microscope-TEM) and by spectrophotometric investigation of the alkaline phosphatasis (ALP).The data show that the coral granules and among the growth factors used only TGF beta 1 stimulate the differentiation activity of the periodontal ligament cells valued on the basis of their capacity of producing ALP. These data are supported by the observation with TEM.From these results it is suggested that there may be therapeutic efficiency in the periodontal field of substances promoting cellular proliferation and differentiation
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