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  1. Article ; Online: New Pieces for an Old Puzzle: Approaching Parkinson's Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics.

    Ortega Moreno, Lorena / Bagues, Ana / Martínez, Vicente / Abalo, Raquel

    Nutrients

    2023  Volume 15, Issue 12

    Abstract: Parkinson's disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract ( ... ...

    Abstract Parkinson's disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD.
    MeSH term(s) Animals ; Parkinson Disease/pathology ; Gastrointestinal Microbiome ; Lipidomics ; Neurodegenerative Diseases ; Models, Animal ; Biomarkers ; Disease Models, Animal
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-06-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu15122775
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cannabinoid drugs against chemotherapy-induced adverse effects: focus on nausea/vomiting, peripheral neuropathy and chemofog in animal models.

    Bagues, Ana / López-Tofiño, Yolanda / Llorente-Berzal, Álvaro / Abalo, Raquel

    Behavioural pharmacology

    2022  Volume 33, Issue 2&3, Page(s) 105–129

    Abstract: Although new drugs are being developed for cancer treatment, classical chemotherapeutic agents are still front-line therapies, despite their frequent association with severe side effects that can hamper their use. Cannabinoids may prevent or palliate ... ...

    Abstract Although new drugs are being developed for cancer treatment, classical chemotherapeutic agents are still front-line therapies, despite their frequent association with severe side effects that can hamper their use. Cannabinoids may prevent or palliate some of these side effects. The aim of the present study is to review the basic research which has been conducted evaluating the effects of cannabinoid drugs in the treatment of three important side effects induced by classical chemotherapeutic agents: nausea and vomiting, neuropathic pain and cognitive impairment. Several published studies have demonstrated that cannabinoids are useful in preventing and reducing the nausea, vomits and neuropathy induced by different chemotherapy regimens, though other side effects can occur, such as a reduction of gastrointestinal motility, along with psychotropic effects when using centrally-acting cannabinoids. Thus, peripherally-acting cannabinoids and new pharmacological options are being investigated, such as allosteric or biased agonists. Additionally, due to the increase in the survival of cancer patients, there are emerging data that demonstrate an important cognitive deterioration due to chemotherapy, and because the cannabinoid drugs have a neuroprotective effect, they could be useful in preventing chemotherapy-induced cognitive impairment (as demonstrated through studies in other neurological disorders), but this has not yet been tested. Thus, although cannabinoids seem a promising therapeutic approach in the treatment of different side effects induced by chemotherapeutic agents, future research will be necessary to find pharmacological options with a safer profile. Moreover, a new line of research awaits to be opened to elucidate their possible usefulness in preventing cognitive impairment.
    MeSH term(s) Animals ; Antiemetics/pharmacology ; Antineoplastic Agents/adverse effects ; Cannabinoids/adverse effects ; Humans ; Models, Animal ; Nausea/chemically induced ; Nausea/drug therapy ; Nausea/prevention & control ; Neuralgia/drug therapy ; Vomiting/chemically induced ; Vomiting/drug therapy ; Vomiting/prevention & control
    Chemical Substances Antiemetics ; Antineoplastic Agents ; Cannabinoids
    Language English
    Publishing date 2022-01-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1027374-8
    ISSN 1473-5849 ; 0955-8810
    ISSN (online) 1473-5849
    ISSN 0955-8810
    DOI 10.1097/FBP.0000000000000667
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Radiographic assessment of the impact of sex and the circadian rhythm-dependent behaviour on gastrointestinal transit in the rat

    Gálvez-Robleño, Carlos / López-Tofiño, Yolanda / López-Gómez, Laura / Bagüés, Ana / Soto-Montenegro, María Luisa / Abalo, Raquel

    Laboratory Animals. 2023 June, v. 57, no. 3 p.270-282

    2023  

    Abstract: Relatively little is known about the influence of sex and the circadian rhythm on gastrointestinal transit. However, these factors could have an important impact on aspects such as digestion, oral absorption of drugs or the clinical manifestation of ... ...

    Abstract Relatively little is known about the influence of sex and the circadian rhythm on gastrointestinal transit. However, these factors could have an important impact on aspects such as digestion, oral absorption of drugs or the clinical manifestation of gastrointestinal diseases, among others. Remarkably, preclinical models have scarcely taken these factors into consideration. In this study, we assessed the gastrointestinal transit of young adult Wistar Han rats of both sexes, under normal and inverted light cycle. To do this, serial radiographs were taken for 24 h (T0–T24) after intragastric barium administration and subsequently analysed to construct transit curves for each gastrointestinal region. Under a normal light cycle, transit curves were similar, except for a slower transit in females compared with males from T8 to T24. Under the inverted cycle, there was a significant acceleration in stomach emptying (similar in both sexes), emptying of the small intestine (even faster in females) and filling of the caecum and colon (which was also even faster in females). This study confirms, using X-ray non-invasive methods for the first time, that both sex and circadian rhythm (probably through its effect on behaviour) influence gastrointestinal transit in laboratory animals.
    Keywords X-radiation ; absorption ; barium ; cecum ; circadian rhythm ; colon ; digestion ; gastrointestinal transit ; laboratories ; photoperiod ; radiography ; rats ; small intestine ; stomach ; young adults ; radiographic methods ; rat ; sex
    Language English
    Dates of publication 2023-06
    Size p. 270-282.
    Publishing place SAGE Publications
    Document type Article ; Online
    ZDB-ID 391008-8
    ISSN 1758-1117 ; 0023-6772
    ISSN (online) 1758-1117
    ISSN 0023-6772
    DOI 10.1177/00236772221124381
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Effects of two different acute and subchronic stressors on gastrointestinal transit in the rat: A radiographic analysis.

    Bagues, Ana / Lopez-Tofiño, Yolanda / Galvez-Robleño, Carlos / Abalo, Raquel

    Neurogastroenterology and motility

    2021  Volume 33, Issue 11, Page(s) e14232

    Abstract: Background: The reaction to stress is an adaptive response necessary for survival. When stressors are repeated, the organism adapts, although these adaptive responses can become dysregulated and result in disease, causing gastrointestinal (GI) disorders. ...

    Abstract Background: The reaction to stress is an adaptive response necessary for survival. When stressors are repeated, the organism adapts, although these adaptive responses can become dysregulated and result in disease, causing gastrointestinal (GI) disorders. Radiographic methods allow the non-invasive study of how a given factor affects GI transit in the same animal at different time points. These methods have never been applied to study the consequences of stress on GI motor function and their dependency on time and stimulus. Therefore, our aim was to characterize, using radiographic techniques, the effect on GI transit of cold-restraint (CR) and forced swim (FS) stress applied acutely and subchronically in the rat.
    Methods: Male Wistar rats (260-330 g) were submitted to FS or CR stress, during 1 (acute) or 4 (subchronic) consecutive days. To study GI transit, radiographic methods were used. Radiographs were taken 0-24 h after barium intragastric administration on the 1st or 4th day of stress, which was applied 1 h after contrast.
    Results: Acute FS or CR slowed down gastric and small intestinal emptying but had opposite effects in the caecum: CR tended to accelerate barium transit and feces formation while FS tended to slow these parameters down. When the stimuli were applied subchronically, GI transit was not completely normalized in most of the studied parameters.
    Conclusion and inferences: Mild stress alters GI transit differently depending on the nature of the stressor and its duration. Exposure to mild stressors should be considered as contributing factors to different functional GI disorders.
    MeSH term(s) Animals ; Gastrointestinal Transit ; Male ; Rats, Wistar ; Restraint, Physical ; Stress, Psychological/physiopathology ; Rats
    Language English
    Publishing date 2021-08-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1186328-6
    ISSN 1365-2982 ; 1350-1925
    ISSN (online) 1365-2982
    ISSN 1350-1925
    DOI 10.1111/nmo.14232
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Mechanisms of Chemotherapy-Induced Neurotoxicity.

    Was, Halina / Borkowska, Agata / Bagues, Ana / Tu, Longlong / Liu, Julia Y H / Lu, Zengbing / Rudd, John A / Nurgali, Kulmira / Abalo, Raquel

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 750507

    Abstract: Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of ... ...

    Abstract Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogs may cause direct and indirect neurotoxicity. In this review we discuss the main effects of chemotherapy on the peripheral and central nervous systems, including neuropathic pain, chemobrain, enteric neuropathy, as well as nausea and emesis. Understanding mechanisms involved in chemotherapy-induced neurotoxicity is crucial for the development of drugs that can protect the nervous system, reduce symptoms experienced by millions of patients, and improve the outcome of the treatment and patients' quality of life.
    Language English
    Publishing date 2022-03-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.750507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Radiographic assessment of the impact of sex and the circadian rhythm-dependent behaviour on gastrointestinal transit in the rat.

    Gálvez-Robleño, Carlos / López-Tofiño, Yolanda / López-Gómez, Laura / Bagüés, Ana / Soto-Montenegro, María Luisa / Abalo, Raquel

    Laboratory animals

    2022  Volume 57, Issue 3, Page(s) 270–282

    Abstract: Relatively little is known about the influence of sex and the circadian rhythm on gastrointestinal transit. However, these factors could have an important impact on aspects such as digestion, oral absorption of drugs or the clinical manifestation of ... ...

    Abstract Relatively little is known about the influence of sex and the circadian rhythm on gastrointestinal transit. However, these factors could have an important impact on aspects such as digestion, oral absorption of drugs or the clinical manifestation of gastrointestinal diseases, among others. Remarkably, preclinical models have scarcely taken these factors into consideration. In this study, we assessed the gastrointestinal transit of young adult Wistar Han rats of both sexes, under normal and inverted light cycle. To do this, serial radiographs were taken for 24 h (T0-T24) after intragastric barium administration and subsequently analysed to construct transit curves for each gastrointestinal region. Under a normal light cycle, transit curves were similar, except for a slower transit in females compared with males from T8 to T24. Under the inverted cycle, there was a significant acceleration in stomach emptying (similar in both sexes), emptying of the small intestine (even faster in females) and filling of the caecum and colon (which was also even faster in females). This study confirms, using X-ray non-invasive methods for the first time, that both sex and circadian rhythm (probably through its effect on behaviour) influence gastrointestinal transit in laboratory animals.
    MeSH term(s) Male ; Female ; Rats ; Animals ; Gastrointestinal Transit ; Rats, Wistar ; Gastrointestinal Tract ; Digestion ; Circadian Rhythm
    Language English
    Publishing date 2022-10-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 391008-8
    ISSN 1758-1117 ; 0023-6772
    ISSN (online) 1758-1117
    ISSN 0023-6772
    DOI 10.1177/00236772221124381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Short-term stress significantly decreases morphine analgesia in trigeminal but not in spinal innervated areas in rats.

    Bagues, Ana / Girón, Rocío / Abalo, Raquel / Goicoechea, Carlos / Martín-Fontelles, María Isabel / Sánchez-Robles, Eva María

    Behavioural brain research

    2022  Volume 435, Page(s) 114046

    Abstract: Plenty information exists regarding the effects of chronic stress, although few data exist on the effects of short-lasting stressors, which would mimic daily challenges. Differences in craniofacial and spinal nociception have been observed, thus those ... ...

    Abstract Plenty information exists regarding the effects of chronic stress, although few data exist on the effects of short-lasting stressors, which would mimic daily challenges. Differences in craniofacial and spinal nociception have been observed, thus those observations obtained in spinally innervated areas cannot be directly applied to the orofacial region. Although, opioids are considered amongst the most effective analgesics, their use is sometimes hampered by the constipation they induce. Thus, our aims were to study if a short-lasting stressor, forced swim stress (FSS), modifies nociception, morphine antinociception and constipation in rats. Animals were submitted to 10-20 min of FSS for three days, nociception and gastrointestinal transit were studied 24 h after the last swimming session. Nociception and morphine (0.6-5 mg/kg) antinociception were evaluated in the formalin and hypertonic saline tests in the orofacial area and limbs. Morphine-induced modifications in the GI transit were studied through radiographic techniques. Naloxone was administered, before each swimming session, to analyse the involvement of the endogenous opioid system on the effect of stress. Overall, stress did not alter nociception, although interestingly it reduced the effect of morphine in the orofacial tests and in the inflammatory phase of the formalin tests. Naloxone antagonized the effect of stress and normalized the effect of morphine. Stress did not modify the constipation induced by morphine. Opioid treatment may be less effective under a stressful situation, whilst adverse effects, such as constipation, are maintained. The prevention of stress may improve the level of opioid analgesia.
    MeSH term(s) Analgesia ; Analgesics, Opioid/pharmacology ; Animals ; Constipation ; Morphine/pharmacology ; Naloxone/pharmacology ; Pain ; Rats
    Chemical Substances Analgesics, Opioid ; Naloxone (36B82AMQ7N) ; Morphine (76I7G6D29C)
    Language English
    Publishing date 2022-08-04
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2022.114046
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  8. Article ; Online: Evaluation of the Effects of Instant Cascara Beverage on the Brain-Gut Axis of Healthy Male and Female Rats.

    Gallego-Barceló, Paula / Bagues, Ana / Benítez-Álvarez, David / López-Tofiño, Yolanda / Gálvez-Robleño, Carlos / López-Gómez, Laura / Del Castillo, María Dolores / Abalo, Raquel

    Nutrients

    2023  Volume 16, Issue 1

    Abstract: Instant cascara (IC) is a sustainable beverage obtained from dried coffee cherry pulp, rich in nutrients and bioactive compounds. The present research aimed to determine the effects of IC on general health and brain-gut axis parameters of healthy female ... ...

    Abstract Instant cascara (IC) is a sustainable beverage obtained from dried coffee cherry pulp, rich in nutrients and bioactive compounds. The present research aimed to determine the effects of IC on general health and brain-gut axis parameters of healthy female and male rats. Wistar rats were exposed to IC (10 mg/mL) in their drinking water for 3 weeks. Body weight and solid and liquid intakes were monitored as indicators of food safety. Gastrointestinal transit was radiographically evaluated one day (acute) and 3 weeks (chronic) after the start of IC exposure. Locomotor activity, anxiety, and anhedonia of the animals after 3 weeks of treatment was also studied. Overall, compared to water-exposed animals, IC significantly increased food intake in males (
    MeSH term(s) Female ; Male ; Rats ; Animals ; Rats, Wistar ; Brain-Gut Axis ; Beverages ; Body Weight ; Health Status
    Language English
    Publishing date 2023-12-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu16010065
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  9. Article: Contractility of isolated colonic smooth muscle strips from rats treated with cancer chemotherapy: differential effects of cisplatin and vincristine.

    López-Tofiño, Yolanda / Barragán Del Caz, Luis Felipe / Benítez-Álvarez, David / Molero-Mateo, Paula / Nurgali, Kulmira / Vera, Gema / Bagües, Ana / Abalo, Raquel

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1304609

    Abstract: Background: Certain antineoplastic drugs cause gastrointestinal disorders even after the end of treatment. Enteric neuropathy has been associated with some of these alterations. Our goal was to assess the impact of repeated treatment with cisplatin and ... ...

    Abstract Background: Certain antineoplastic drugs cause gastrointestinal disorders even after the end of treatment. Enteric neuropathy has been associated with some of these alterations. Our goal was to assess the impact of repeated treatment with cisplatin and vincristine on the contractility of circular and longitudinal muscle strips isolated from the rat colon.
    Methods: Two cohorts of male rats were used: in cohort 1, rats received one intraperitoneal (
    Results: Both drugs decreased body weight gain. Compared to saline, cisplatin significantly decreased responses of both longitudinal and circular smooth muscle strips to EFS, whereas vincristine tended to increase them, although in a non-significant manner. No differences were observed in the muscle response to acetylcholine. Atropine abolished the contractile responses induced by acetylcholine, although those induced by EFS were only partially reduced in the presence of atropine.
    Conclusion: The findings suggest that although both drugs cause the development of enteric neuropathy, this seems to have a functional impact only in cisplatin-treated animals. Understanding the effects of chemotherapy on gastrointestinal motor function is vital for enhancing the quality of life of cancer patients.
    Language English
    Publishing date 2023-12-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1304609
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  10. Article ; Online: Maternal separation affects the electrophysiological properties of Aδ-fibres and nociceptive behaviours in male and female mice.

    Paniagua, Nancy / Girón, Rocío / Goicoechea, Carlos / Martín-Fontelles, Mª Isabel / Bagues, Ana

    International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience

    2020  Volume 80, Issue 6, Page(s) 538–546

    Abstract: Aim: Early life adverse effects have been associated with an increased risk of suffering pain syndromes in adulthood. Although animal models are of great importance to study modifications of pain sensitivity, up to date the results obtained are ... ...

    Abstract Aim: Early life adverse effects have been associated with an increased risk of suffering pain syndromes in adulthood. Although animal models are of great importance to study modifications of pain sensitivity, up to date the results obtained are contradicting due to the varied methodologies used. Therefore, the aim of the present study was to characterise, as a whole, possible modifications in visceral and somatic nociceptive responses in male and female ICR mice, submitted to two different protocols of maternal separation (MS), and possible modifications in the electrophysiological properties of peripheral nociceptive Aδ-primary afferents.
    Main methods: Male and female mice were submitted to 3 or 4-8 hr of daily MS from postnatal day (PND) 2-17 and early weaned. On PND 67 von Frey, hot plate and writhing tests were performed. Afterwards electrophysiological recordings were carried out, using the in vitro skin-saphenous nerve preparation in males.
    Key findings: The short separation protocol of MS did not modify nociceptive sensitivity; but when mice were separated from their dams for the long separation, mechanical pain thresholds were modified in male and female mice and visceral nociception was increased in female mice. Electrophysiological recordings showed that cutaneous Aδ-fibres were sensitised and their mechanotransduction properties were altered in both MS protocols.
    Significance: Although MS increases the activity and the mechanosensitivity of cutaneous Aδ-afferent fibres at both short and long periods of separation, only the longer interval of time induces nociceptive sensitivity alterations during adulthood. These results highlight the possible influence of a stress free environment during childhood to reduce nociceptive alterations in adulthood.
    MeSH term(s) Action Potentials/physiology ; Animals ; Behavior, Animal/physiology ; Female ; Male ; Maternal Deprivation ; Mice ; Nerve Fibers, Myelinated/physiology ; Nociception/physiology ; Nociceptors/physiology ; Pain Threshold/physiology
    Language English
    Publishing date 2020-07-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605533-3
    ISSN 1873-474X ; 0736-5748
    ISSN (online) 1873-474X
    ISSN 0736-5748
    DOI 10.1002/jdn.10049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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