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  1. Article ; Online: Fasting duration impacts ribosome protein 6 phosphorylation in zebrafish brain: New insights in aquatic organisms' welfare.

    Raggio, Maria / Giaquinto, Daniela / Attanasio, Chiara / Palladino, Antonio / Esposito, Vincenzo / Radaelli, Giuseppe / De Felice, Elena / de Girolamo, Paolo / D'Angelo, Livia

    Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft

    2024  Volume 254, Page(s) 152266

    Abstract: Background: Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic ... ...

    Abstract Background: Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic neurons. In the field of neuroscience, ribosomal protein S6 (S6) phosphorylation is commonly used as a readout of the mammalian target of rapamycin complex 1 signalling activation or as a marker for neuronal activity. The aim of this study is addressed to evaluate whether the phosphorylation of S6 occurs in the central neurons of zebrafish exposed to four (short-term) and seven (mid-term) days of complete fasting.
    Methods: Group-housed adult zebrafish were exposed to four and seven days of complete food withdrawal. At the end of the experimental period, Western blotting analyses were carried out to measure the expression levels of the phosphorylated S6 (pS6) by comparing the two experimental conditions versus the control group. The same antibody was then used to identify the distribution pattern of pS6 immunoreactive neurons in the whole brain and in the taste buds.
    Results: We did not observe increased pS6 levels expression in the brain of animals exposed to short-term fasting compared to the control, whereas the expression increased in brain homogenates of animals exposed to mid-term fasting. pS6 immunoreactivity was reported in some hypothalamic neurons, as well as in the dorsal area of telencephalon and preoptic area, a neurosecretory region homolog to the mammalian paraventricular nucleus. Remarkably, we observed pS6 immunostaining in the sensory cells of taste buds lining the oral epithelium.
    Conclusions: Taken together, our data show that in zebrafish, differently from other fish species, seven days of fasting triggers neuronal activity. Furthermore, the immunostaining on sensory cells of taste buds suggests that metabolic changes may modulate also peripheral sensory cells. This event may have valuable implications when using zebrafish to design metabolic studies involving fasting as well as practical consequences on the animal welfare, in particularly stressful conditions, such as transportation.
    Language English
    Publishing date 2024-04-18
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1106738-x
    ISSN 1618-0402 ; 0940-9602
    ISSN (online) 1618-0402
    ISSN 0940-9602
    DOI 10.1016/j.aanat.2024.152266
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Progesterone receptor-mediated actions and the treatment of central nervous system disorders: An up-date of the known and the challenge of the unknown.

    González, Susana L / Coronel, María F / Raggio, María C / Labombarda, Florencia

    Steroids

    2019  Volume 153, Page(s) 108525

    Abstract: Progesterone has been shown to exert a wide range of remarkable protective actions in experimental models of central nervous system injury or disease. However, the intimate mechanisms involved in each of these beneficial effects are not fully depicted. ... ...

    Abstract Progesterone has been shown to exert a wide range of remarkable protective actions in experimental models of central nervous system injury or disease. However, the intimate mechanisms involved in each of these beneficial effects are not fully depicted. In this review, we intend to give the readers a thorough revision on what is known about the participation of diverse receptors and signaling pathways in progesterone-mediated neuroprotective, pro-myelinating and anti-inflammatory outcomes, as well as point out to novel regulatory mechanisms that could open new perspectives in steroid-based therapies.
    MeSH term(s) Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Central Nervous System Diseases/drug therapy ; Central Nervous System Diseases/metabolism ; Central Nervous System Diseases/pathology ; Humans ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Progesterone/chemistry ; Progesterone/pharmacology ; Receptors, Progesterone/metabolism
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Neuroprotective Agents ; Receptors, Progesterone ; Progesterone (4G7DS2Q64Y)
    Language English
    Publishing date 2019-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80312-1
    ISSN 1878-5867 ; 0039-128X
    ISSN (online) 1878-5867
    ISSN 0039-128X
    DOI 10.1016/j.steroids.2019.108525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Anti-allodynic and anti-inflammatory effects of 17α-hydroxyprogesterone caproate in oxaliplatin-induced peripheral neuropathy.

    Miguel, Constanza A / Raggio, María C / Villar, Marcelo J / Gonzalez, Susana L / Coronel, María F

    Journal of the peripheral nervous system : JPNS

    2019  Volume 24, Issue 1, Page(s) 100–110

    Abstract: Chemotherapy-induced peripheral neuropathy is a disabling condition induced by several frequently used chemotherapeutic drugs including the front-line agent oxaliplatin (OXA). Symptoms are predominantly sensory with the development of neuropathic pain. ... ...

    Abstract Chemotherapy-induced peripheral neuropathy is a disabling condition induced by several frequently used chemotherapeutic drugs including the front-line agent oxaliplatin (OXA). Symptoms are predominantly sensory with the development of neuropathic pain. Alternative dosing protocols and treatment discontinuation are the only available therapeutic strategies. The aim of our work was to evaluate the potential of a synthetic derivative of progesterone, 17α-hydroxyprogesterone caproate (HPGC), in the prevention and treatment of OXA-evoked painful neuropathy. We also evaluated glial activation at the dorsal root ganglia (DRG) and spinal cord levels as a possible target mechanism underlying HPGC actions. Male rats were injected with OXA and HPGC following a prophylactic (HPGCp) or therapeutic (HPGCt) scheme (starting either before or after chemotherapy). The development of hypersensitivity and allodynic pain and the expression of neuronal and glial activation markers were evaluated. When compared to control animals, those receiving OXA showed a significant decrease in paw mechanical and thermal thresholds, with the development of allodynia. Animals treated with HPGCp showed patterns of response similar to those detected in control animals, while those treated with HPGCt showed a suppression of both hypersensitivities after HPGC administration. We also observed a significant increase in the mRNA levels of activating transcription factor 3, the transcription factor (c-fos), glial fibrillary acidic protein, ionized calcium binding adaptor protein 1, interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) in DRG and spinal cord of OXA-injected animals, and significantly lower levels in rats receiving OXA and HPGC. These results show that HPGC administration reduces neuronal and glial activation markers and is able to both prevent and suppress OXA-induced allodynia, suggesting a promising therapeutic strategy.
    MeSH term(s) 17 alpha-Hydroxyprogesterone Caproate/administration & dosage ; 17 alpha-Hydroxyprogesterone Caproate/pharmacology ; Animals ; Antineoplastic Agents/pharmacology ; Behavior, Animal/drug effects ; Disease Models, Animal ; Hyperalgesia/chemically induced ; Hyperalgesia/drug therapy ; Hyperalgesia/prevention & control ; Male ; Neuralgia/chemically induced ; Neuralgia/drug therapy ; Neuralgia/prevention & control ; Oxaliplatin/pharmacology ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/drug therapy ; Peripheral Nervous System Diseases/prevention & control ; Progestins/administration & dosage ; Progestins/pharmacology ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Antineoplastic Agents ; Progestins ; Oxaliplatin (04ZR38536J) ; 17 alpha-Hydroxyprogesterone Caproate (276F2O42F5)
    Language English
    Publishing date 2019-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1364009-4
    ISSN 1529-8027 ; 1085-9489
    ISSN (online) 1529-8027
    ISSN 1085-9489
    DOI 10.1111/jns.12307
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Genetic Variations of OPRM1, OPRK1, and COMT Genes and Their Possible Associations with Oral Pain in a Population from Argentina.

    Raggio, María Celeste / González, Rebeca / Hohl, Diana María / Glesmann, Laura Angela / Catanesi, Cecilia Inés

    Journal of oral & facial pain and headache

    2018  Volume 32, Issue 4, Page(s) 367–374

    Abstract: Aims: To analyze in a population from Argentina the variation of three genes involved in the control of pain pathways-two genes that code for opioid receptors (OPRM1 and OPRK1) and COMT, which codes for an important enzyme in the control of ... ...

    Abstract Aims: To analyze in a population from Argentina the variation of three genes involved in the control of pain pathways-two genes that code for opioid receptors (OPRM1 and OPRK1) and COMT, which codes for an important enzyme in the control of neurotransmission-and to evaluate the associations of these genes with oral pain and the need for analgesics in the population under study.
    Methods: A total of 134 volunteer donors from the city of Resistencia and 27 donors from the Wichí community for comparison were analyzed for 13 single nucelotide polymorphisms (SNPs) and 1 insertion/deletion (Indel) localized in the three genes using polymerase chain reaction-restriction fragment length polymorphism or standard PCR and electrophoresis. All 134 individuals from Resistencia provided biologic samples for DNA analysis, and a subset (n = 81) agreed to answer a questionnaire for an association analysis. Statistical tests for a possible association between genetic variation and self-reported ethnic origin, oral pain, and need for analgesic drugs were performed.
    Results: Significant differences were found when the study population was compared to populations from other continents, as well as between the two studied populations (P < .05). A positive association was suggested for the COMT gene from Resistencia with both oral pain intensity and analgesic requirements.
    Conclusion: The admixture process that occurred in the past of Resistencia probably contributed to a genetic differentiation in this population, and this genetic variation might influence phenotypic expressions of pain perception and analgesic requirements.
    MeSH term(s) Analgesics/therapeutic use ; Argentina ; Catechol O-Methyltransferase/genetics ; Humans ; Mouth Diseases/drug therapy ; Mouth Diseases/genetics ; Pain/drug therapy ; Pain/genetics ; Pain Perception ; Polymorphism, Single Nucleotide ; Receptors, Opioid, kappa/genetics ; Receptors, Opioid, mu/genetics
    Chemical Substances Analgesics ; OPRK1 protein, human ; OPRM1 protein, human ; Receptors, Opioid, kappa ; Receptors, Opioid, mu ; COMT protein, human (EC 2.1.1.6) ; Catechol O-Methyltransferase (EC 2.1.1.6)
    Language English
    Publishing date 2018-10-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2762048-7
    ISSN 2333-0376 ; 2333-0384
    ISSN (online) 2333-0376
    ISSN 2333-0384
    DOI 10.11607/ofph.1902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Allopregnanolone and Progesterone in Experimental Neuropathic Pain: Former and New Insights with a Translational Perspective.

    González, Susana Laura / Meyer, Laurence / Raggio, María Celeste / Taleb, Omar / Coronel, María Florencia / Patte-Mensah, Christine / Mensah-Nyagan, Ayikoe Guy

    Cellular and molecular neurobiology

    2018  Volume 39, Issue 4, Page(s) 523–537

    Abstract: In the last decades, an active and stimulating area of research has been devoted to explore the role of neuroactive steroids in pain modulation. Despite challenges, these studies have clearly contributed to unravel the multiple and complex actions and ... ...

    Abstract In the last decades, an active and stimulating area of research has been devoted to explore the role of neuroactive steroids in pain modulation. Despite challenges, these studies have clearly contributed to unravel the multiple and complex actions and potential mechanisms underlying steroid effects in several experimental conditions that mimic human chronic pain states. Based on the available data, this review focuses mainly on progesterone and its reduced derivative allopregnanolone (also called 3α,5α-tetrahydroprogesterone) which have been shown to prevent or even reverse the complex maladaptive changes and pain behaviors that arise in the nervous system after injury or disease. Because the characterization of new related molecules with improved specificity and enhanced pharmacological profiles may represent a crucial step to develop more efficient steroid-based therapies, we have also discussed the potential of novel synthetic analogs of allopregnanolone as valuable molecules for the treatment of neuropathic pain.
    MeSH term(s) Animals ; Humans ; Models, Biological ; Neuralgia/drug therapy ; Neuralgia/metabolism ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Pregnanolone/biosynthesis ; Pregnanolone/metabolism ; Progesterone/biosynthesis ; Progesterone/chemistry ; Progesterone/metabolism ; Translational Medical Research
    Chemical Substances Neuroprotective Agents ; Progesterone (4G7DS2Q64Y) ; Pregnanolone (BXO86P3XXW)
    Language English
    Publishing date 2018-09-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 283404-2
    ISSN 1573-6830 ; 0272-4340
    ISSN (online) 1573-6830
    ISSN 0272-4340
    DOI 10.1007/s10571-018-0618-1
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  6. Article ; Online: Temporal changes in the expression of the translocator protein TSPO and the steroidogenic enzyme 5α-reductase in the dorsal spinal cord of animals with neuropathic pain: Effects of progesterone administration.

    Coronel, María F / Sánchez Granel, María L / Raggio, María C / Adler, Natalia S / De Nicola, Alejandro F / Labombarda, Florencia / González, Susana L

    Neuroscience letters

    2016  Volume 624, Page(s) 23–28

    Abstract: Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. The presence and biological activity of steroidogenic regulatory proteins and enzymes in the spinal cord suggests that neurosteroids ... ...

    Abstract Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. The presence and biological activity of steroidogenic regulatory proteins and enzymes in the spinal cord suggests that neurosteroids locally generated could modulate pain messages. In this study we explored temporal changes in the spinal expression of the 18kDa translocator protein TSPO, the steroidogenic acute regulatory protein (StAr) and the steroidogenic enzyme 5α-reductase (5α-RI/II) in an experimental model of central chronic pain. Male Sprague-Dawley rats were subjected to a SCI and sacrificed at different time points (1, 14 or 28days). The development of mechanical and cold allodynia was assessed. Injured animals showed an early increase in the mRNA levels of TSPO and 5α-RII, whereas in the chronic phase a significant decrease in the expression of 5α-RI and 5α-RII was observed, coinciding with the presence of allodynic behaviors. Furthermore, since we have shown that progesterone (PG) administration may offer a promising perspective in pain modulation, we also evaluated the expression of steroidogenic proteins and enzymes in injured animals receiving daily injections of the steroid. PG-treated did not develop allodynia and showed a marked increase in the mRNA levels of TSPO, StAR, 5α-RI and 5α-RII 28days after injury. Our results suggest that in the acute phase after SCI, the increased expression of TSPO and 5α-RII may represent a protective endogenous response against tissue injury, which is not maintained in the chronic allodynic phase. PG may favor local steroidogenesis and the production of its reduced metabolites, which could contribute to the antiallodynic effects observed after PG treatment.
    MeSH term(s) Animals ; Carrier Proteins/metabolism ; Cholestenone 5 alpha-Reductase/metabolism ; Hyperalgesia/enzymology ; Hyperalgesia/etiology ; Hyperalgesia/metabolism ; Male ; Neuralgia/enzymology ; Neuralgia/etiology ; Neuralgia/metabolism ; Neuralgia/prevention & control ; Pain Threshold/drug effects ; Progesterone/administration & dosage ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A/metabolism ; Spinal Cord Injuries/complications ; Spinal Cord Injuries/enzymology ; Spinal Cord Injuries/metabolism
    Chemical Substances Carrier Proteins ; RNA, Messenger ; Receptors, GABA-A ; Tspo protein, rat (141440-82-6) ; Progesterone (4G7DS2Q64Y) ; Cholestenone 5 alpha-Reductase (EC 1.3.1.22)
    Language English
    Publishing date 2016-06-15
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2016.04.067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Progesterone modulates pro-inflammatory cytokine expression profile after spinal cord injury: Implications for neuropathic pain.

    Coronel, María F / Raggio, María C / Adler, Natalia S / De Nicola, Alejandro F / Labombarda, Florencia / González, Susana L

    Journal of neuroimmunology

    2016  Volume 292, Page(s) 85–92

    Abstract: Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. Glial cell activation and cytokine production contribute to the pathology of central neuropathic syndromes. In this study we evaluated ... ...

    Abstract Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. Glial cell activation and cytokine production contribute to the pathology of central neuropathic syndromes. In this study we evaluated the effects of progesterone, a neuroactive steroid, on pain development and the spinal expression of IL-1β, its receptors (IL-1RI and IL-1RII) and antagonist (IL-1ra), IL-6 and TNFα, and NR1 subunit of NMDAR. Our results show that progesterone, by modulating the expression of pro-inflammatory cytokines and neuronal IL-1RI/NR1 colocalization, emerges as a promising agent to prevent chronic pain after SCI.
    MeSH term(s) Animals ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Hyperalgesia/drug therapy ; Hyperalgesia/etiology ; Male ; Neuralgia/etiology ; Pain Threshold/drug effects ; Phosphopyruvate Hydratase/genetics ; Phosphopyruvate Hydratase/metabolism ; Progesterone/therapeutic use ; Progestins/therapeutic use ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Spinal Cord Injuries/complications ; Spinal Cord Injuries/drug therapy ; Spinal Cord Injuries/metabolism ; Time Factors
    Chemical Substances Cytokines ; NR1 NMDA receptor ; Progestins ; RNA, Messenger ; Receptors, N-Methyl-D-Aspartate ; Progesterone (4G7DS2Q64Y) ; Phosphopyruvate Hydratase (EC 4.2.1.11)
    Language English
    Publishing date 2016-03-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/j.jneuroim.2016.01.011
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