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  1. Article: Antagonistic Roles of P2X7 and P2Y2 Receptors in Neurodegenerative Diseases.

    Glaser, Talita / Oliveira-Giacomelli, Ágatha / Petiz, Lyvia Lintzmaier / Ribeiro, Deidiane Elisa / Andrejew, Roberta / Ulrich, Henning

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 659097

    Language English
    Publishing date 2021-04-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.659097
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer's disease.

    Campos, Henrique Correia / Ribeiro, Deidiane Elisa / Hashiguchi, Debora / Glaser, Talita / Milanis, Milena da Silva / Gimenes, Christiane / Suchecki, Deborah / Arida, Ricardo Mario / Ulrich, Henning / Monteiro Longo, Beatriz

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1132825

    Abstract: ... for immunohistochemical analysis of Aβ plaques and microglia, and blood was collected for plasma corticosterone by ELISA ...

    Abstract Introduction: Physical exercise has beneficial effects by providing neuroprotective and anti-inflammatory responses to AD. Most studies, however, have been conducted with aerobic exercises, and few have investigated the effects of other modalities that also show positive effects on AD, such as resistance exercise (RE). In addition to its benefits in developing muscle strength, balance and muscular endurance favoring improvements in the quality of life of the elderly, RE reduces amyloid load and local inflammation, promotes memory and cognitive improvements, and protects the cortex and hippocampus from the degeneration that occurs in AD. Similar to AD patients, double-transgenic APPswe/PS1dE9 (APP/PS1) mice exhibit Αβ plaques in the cortex and hippocampus, hyperlocomotion, memory deficits, and exacerbated inflammatory response. Therefore, the aim of this study was to investigate the effects of 4 weeks of RE intermittent training on the prevention and recovery from these AD-related neuropathological conditions in APP/PS1 mice.
    Methods: For this purpose, 6-7-month-old male APP/PS1 transgenic mice and their littermates, negative for the mutations (CTRL), were distributed into three groups: CTRL, APP/PS1, APP/PS1+RE. RE training lasted four weeks and, at the end of the program, the animals were tested in the open field test for locomotor activity and in the object recognition test for recognition memory evaluation. The brains were collected for immunohistochemical analysis of Aβ plaques and microglia, and blood was collected for plasma corticosterone by ELISA assay.
    Results: APP/PS1 transgenic sedentary mice showed increased hippocampal Aβ plaques and higher plasma corticosterone levels, as well as hyperlocomotion and reduced central crossings in the open field test, compared to APP/PS1 exercised and control animals. The intermittent program of RE was able to recover the behavioral, corticosterone and Aβ alterations to the CTRL levels. In addition, the RE protocol increased the number of microglial cells in the hippocampus of APP/PS1 mice. Despite these alterations, no memory impairment was observed in APP/PS1 mice in the novel object recognition test.
    Discussion: Altogether, the present results suggest that RE plays a role in alleviating AD symptoms, and highlight the beneficial effects of RE training as a complementary treatment for AD.
    Language English
    Publishing date 2023-04-06
    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.2023.1132825
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: P2X7 Receptor Signaling in Stress and Depression

    Deidiane Elisa Ribeiro / Aline Lulho Roncalho / Talita Glaser / Henning Ulrich / Gregers Wegener / Sâmia Joca

    International Journal of Molecular Sciences, Vol 20, Iss 11, p

    2019  Volume 2778

    Abstract: Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is ... ...

    Abstract Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is required. Recent studies suggest that adenosine triphosphate (ATP)-mediated signaling through the P2X7 receptor (P2X7R) might play a prominent role in regulating depression-related pathology, such as synaptic plasticity, neuronal degeneration, as well as changes in cognitive and behavioral functions. P2X7R is an ATP-gated cation channel localized in different cell types in the central nervous system (CNS), playing a crucial role in neuron-glia signaling. P2X7R may modulate the release of several neurotransmitters, including monoamines, nitric oxide (NO) and glutamate. Moreover, P2X7R stimulation in microglia modulates the innate immune response by activating the NLR family pyrin domain containing 3 (NLRP3) inflammasome, consistent with the neuroimmune hypothesis of MDD. Importantly, blockade of P2X7R leads to antidepressant-like effects in different animal models, which corroborates the findings that the gene encoding for the P2X7R is located in a susceptibility locus of relevance to depression in humans. This review will discuss recent findings linked to the P2X7R involvement in stress and MDD neuropathophysiology, with special emphasis on neurochemical, neuroimmune, and neuroplastic mechanisms.
    Keywords P2X7 receptor ; depression ; stress ; neuroinflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 572
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer's Disease.

    Campos, Henrique C / Ribeiro, Deidiane Elisa / Hashiguchi, Debora / Hukuda, Deborah Y / Gimenes, Christiane / Romariz, Simone A A / Ye, Qing / Tang, Yong / Ulrich, Henning / Longo, Beatriz Monteiro

    Stem cell reviews and reports

    2022  Volume 18, Issue 2, Page(s) 781–791

    Abstract: Alzheimer's disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal ...

    Abstract Alzheimer's disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal models corresponding to the main aspects of AD in humans have been widely used. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice show cognitive deficits, hyperlocomotion, amyloid-β (Αβ) plaques in the cortex and hippocampus, and exacerbated inflammatory responses. Recent studies have shown that these neuropathological features could be reversed by stem cell transplantation. However, the effects induced by neural (NSC) and mesenchymal (MSC) stem cells has never been compared in an AD animal model. Therefore, the present study aimed to investigate whether transplantation of NSC or MSC into the hippocampus of APP/PS1 mice reverses AD-induced pathological alterations, evaluated by the locomotor activity (open field test), short- and long-term memory (object recognition) tests, Αβ plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotype frequencies. NSC and MSC engraftment reduced the number of Αβ plaques and produced an increase in M2 microglia polarization in the hippocampus of APP/PS1 mice, suggesting an anti-inflammatory effect of stem cell transplantation. NSC also reversed the hyperlocomotor activity and increased the number of microglia in the hippocampus of APP/PS1 mice. No impairment of short or long-term memory was observed in APP/PS1 mice. Overall, this study highlights the potential beneficial effects of transplanting NSC or MSC for AD treatment.
    MeSH term(s) Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Alzheimer Disease/therapy ; Amyloid beta-Peptides/metabolism ; Animals ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, Transgenic ; Plaque, Amyloid/pathology
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2022-01-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2495577-2
    ISSN 2629-3277 ; 1558-6804 ; 1550-8943
    ISSN (online) 2629-3277 ; 1558-6804
    ISSN 1550-8943
    DOI 10.1007/s12015-021-10321-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: P2X7 Receptor Signaling in Stress and Depression.

    Ribeiro, Deidiane Elisa / Roncalho, Aline Lulho / Glaser, Talita / Ulrich, Henning / Wegener, Gregers / Joca, Sâmia

    International journal of molecular sciences

    2019  Volume 20, Issue 11

    Abstract: Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is ... ...

    Abstract Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is required. Recent studies suggest that adenosine triphosphate (ATP)-mediated signaling through the P2X7 receptor (P2X7R) might play a prominent role in regulating depression-related pathology, such as synaptic plasticity, neuronal degeneration, as well as changes in cognitive and behavioral functions. P2X7R is an ATP-gated cation channel localized in different cell types in the central nervous system (CNS), playing a crucial role in neuron-glia signaling. P2X7R may modulate the release of several neurotransmitters, including monoamines, nitric oxide (NO) and glutamate. Moreover, P2X7R stimulation in microglia modulates the innate immune response by activating the NLR family pyrin domain containing 3 (NLRP3) inflammasome, consistent with the neuroimmune hypothesis of MDD. Importantly, blockade of P2X7R leads to antidepressant-like effects in different animal models, which corroborates the findings that the gene encoding for the P2X7R is located in a susceptibility locus of relevance to depression in humans. This review will discuss recent findings linked to the P2X7R involvement in stress and MDD neuropathophysiology, with special emphasis on neurochemical, neuroimmune, and neuroplastic mechanisms.
    MeSH term(s) Animals ; Brain/metabolism ; Depression/metabolism ; Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neurotransmitter Agents/metabolism ; Receptors, Purinergic P2X7/metabolism ; Signal Transduction ; Stress, Psychological/metabolism
    Chemical Substances NLR Family, Pyrin Domain-Containing 3 Protein ; Neurotransmitter Agents ; Receptors, Purinergic P2X7
    Language English
    Publishing date 2019-06-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20112778
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Purinergic signaling in cognitive impairment and neuropsychiatric symptoms of Alzheimer's disease.

    Ribeiro, Deidiane Elisa / Petiz, Lyvia Lintzmaier / Glaser, Talita / Oliveira-Giacomelli, Ágatha / Andrejew, Roberta / Saab, Fernando de Azevedo Ribeiro / Milanis, Milena da Silva / Campos, Henrique Correia / Sampaio, Vanessa Fernandes Arnaud / La Banca, Sophia / Longo, Beatriz Monteiro / Lameu, Claudiana / Tang, Yong / Resende, Rodrigo Ribeiro / Ferreira, Sergio T / Ulrich, Henning

    Neuropharmacology

    2022  Volume 226, Page(s) 109371

    Abstract: About 10 million new cases of dementia develop worldwide each year, of which up to 70% are attributable to Alzheimer's disease (AD). In addition to the widely known symptoms of memory loss and cognitive impairment, AD patients frequently develop non- ... ...

    Abstract About 10 million new cases of dementia develop worldwide each year, of which up to 70% are attributable to Alzheimer's disease (AD). In addition to the widely known symptoms of memory loss and cognitive impairment, AD patients frequently develop non-cognitive symptoms, referred to as behavioral and psychological symptoms of dementia (BPSDs). Sleep disorders are often associated with AD, but mood alterations, notably depression and apathy, comprise the most frequent class of BPSDs. BPSDs negatively affect the lives of AD patients and their caregivers, and have a significant impact on public health systems and the economy. Because treatments currently available for AD are not disease-modifying and mainly aim to ameliorate some of the cognitive symptoms, elucidating the mechanisms underlying mood alterations and other BPSDs in AD may reveal novel avenues for progress in AD therapy. Purinergic signaling is implicated in the pathophysiology of several central nervous system (CNS) disorders, such as AD, depression and sleep disorders. Here, we review recent findings indicating that purinergic receptors, mainly the A
    MeSH term(s) Humans ; Alzheimer Disease/psychology ; Neuropsychological Tests ; Cognitive Dysfunction ; Behavioral Symptoms/etiology ; Sleep Wake Disorders/etiology
    Language English
    Publishing date 2022-12-09
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2022.109371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The P2X7 Receptor: Central Hub of Brain Diseases.

    Andrejew, Roberta / Oliveira-Giacomelli, Ágatha / Ribeiro, Deidiane Elisa / Glaser, Talita / Arnaud-Sampaio, Vanessa Fernandes / Lameu, Claudiana / Ulrich, Henning

    Frontiers in molecular neuroscience

    2020  Volume 13, Page(s) 124

    Abstract: The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the ... ...

    Abstract The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the extracellular milieu. The P2X7 receptor is widely expressed in the CNS, such as frontal cortex, hippocampus, amygdala and striatum, regions involved in neurodegenerative diseases and psychiatric disorders. Despite P2X7 receptor functions in glial cells have been extensively studied, the existence and roles of this receptor in neurons are still controversially discussed. Regardless, P2X7 receptors mediate several processes observed in neuropsychiatric disorders and brain tumors, such as activation of neuroinflammatory response, stimulation of glutamate release and neuroplasticity impairment. Moreover, P2X7 receptor gene polymorphisms have been associated to depression, and isoforms of P2X7 receptors are implicated in neuropsychiatric diseases. In view of that, the P2X7 receptor has been proposed to be a potential target for therapeutic intervention in brain diseases. This review discusses the molecular mechanisms underlying P2X7 receptor-mediated signaling in neurodegenerative diseases, psychiatric disorders, and brain tumors. In addition, it highlights the recent advances in the development of P2X7 receptor antagonists that are able of penetrating the central nervous system.
    Language English
    Publishing date 2020-07-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2020.00124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Reduced P2X receptor levels are associated with antidepressant effect in the learned helplessness model

    Deidiane Elisa Ribeiro / Plinio C. Casarotto / Laura Staquini / Maria Augusta Pinto e Silva / Caroline Biojone / Gregers Wegener / Samia Joca

    PeerJ, Vol 7, p e

    2019  Volume 7834

    Abstract: Purinergic receptors, especially P2RX, are associated to the severity of symptoms in patients suffering from depressive and bipolar disorders, and genetic deletion or pharmacological blockade of P2RX7 induces antidepressant-like effect in preclinical ... ...

    Abstract Purinergic receptors, especially P2RX, are associated to the severity of symptoms in patients suffering from depressive and bipolar disorders, and genetic deletion or pharmacological blockade of P2RX7 induces antidepressant-like effect in preclinical models. However, there is scarce evidence about the alterations in P2RX7 or P2RX4 levels and in behavioral consequences induced by previous exposure to stress, a major risk factor for depression in humans. In the present study, we evaluated the effect of imipramine (IMI) on P2RX7 and P2RX4 levels in dorsal and ventral hippocampus as well as in the frontal cortex of rats submitted to the pretest session of learned helplessness (LH) paradigm. Repeated, but not acute administration of IMI (15 mg/kg ip) reduced the levels of both P2RX7 and P2RX4 in the ventral, but not in dorsal hippocampus or frontal cortex. In addition, we tested the effect of P2RX7/P2RX4 antagonist brilliant blue G (BBG: 25 or 50 mg/kg ip) on the LH paradigm. We observed that repeated (7 days) but not acute (1 day) treatment with BBG (50 mg) reduced the number of failures to escape the shocks in the test session, a parameter mimicked by the same regimen of IMI treatment. Taken together, our data indicates that pharmacological blockade or decrease in the expression of P2RX7 is associated to the antidepressant-like behavior observed in the LH paradigm after repeated drug administration.
    Keywords P2X7 receptor ; P2X4 receptor ; Learned helplessness ; Brilliant blue G ; Imipramine ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 150
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Reduced P2X receptor levels are associated with antidepressant effect in the learned helplessness model.

    Ribeiro, Deidiane Elisa / Casarotto, Plinio C / Staquini, Laura / Pinto E Silva, Maria Augusta / Biojone, Caroline / Wegener, Gregers / Joca, Samia

    PeerJ

    2019  Volume 7, Page(s) e7834

    Abstract: Purinergic receptors, especially P2RX, are associated to the severity of symptoms in patients suffering from depressive and bipolar disorders, and genetic deletion or pharmacological blockade of P2RX7 induces antidepressant-like effect in preclinical ... ...

    Abstract Purinergic receptors, especially P2RX, are associated to the severity of symptoms in patients suffering from depressive and bipolar disorders, and genetic deletion or pharmacological blockade of P2RX7 induces antidepressant-like effect in preclinical models. However, there is scarce evidence about the alterations in P2RX7 or P2RX4 levels and in behavioral consequences induced by previous exposure to stress, a major risk factor for depression in humans. In the present study, we evaluated the effect of imipramine (IMI) on P2RX7 and P2RX4 levels in dorsal and ventral hippocampus as well as in the frontal cortex of rats submitted to the pretest session of learned helplessness (LH) paradigm. Repeated, but not acute administration of IMI (15 mg/kg ip) reduced the levels of both P2RX7 and P2RX4 in the ventral, but not in dorsal hippocampus or frontal cortex. In addition, we tested the effect of P2RX7/P2RX4 antagonist brilliant blue G (BBG: 25 or 50 mg/kg ip) on the LH paradigm. We observed that repeated (7 days) but not acute (1 day) treatment with BBG (50 mg) reduced the number of failures to escape the shocks in the test session, a parameter mimicked by the same regimen of IMI treatment. Taken together, our data indicates that pharmacological blockade or decrease in the expression of P2RX7 is associated to the antidepressant-like behavior observed in the LH paradigm after repeated drug administration.
    Language English
    Publishing date 2019-10-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.7834
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease.

    Glaser, Talita / Andrejew, Roberta / Oliveira-Giacomelli, Ágatha / Ribeiro, Deidiane Elisa / Bonfim Marques, Lucas / Ye, Qing / Ren, Wen-Jing / Semyanov, Alexey / Illes, Peter / Tang, Yong / Ulrich, Henning

    Neuroscience bulletin

    2020  Volume 36, Issue 11, Page(s) 1299–1314

    Abstract: Huntington's (HD) and Parkinson's diseases (PD) are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms, respectively. We review here the ... ...

    Abstract Huntington's (HD) and Parkinson's diseases (PD) are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms, respectively. We review here the participation of purinergic receptors through intracellular Ca
    MeSH term(s) Basal Ganglia/metabolism ; Basal Ganglia/physiopathology ; Calcium Signaling ; GABAergic Neurons ; Globus Pallidus/metabolism ; Humans ; Huntington Disease/physiopathology ; Parkinson Disease/physiopathology ; Receptor, Adenosine A2A ; Receptors, Dopamine D2/metabolism ; Receptors, Glutamate ; Receptors, Purinergic/metabolism ; Receptors, Purinergic P2X7
    Chemical Substances Receptor, Adenosine A2A ; Receptors, Dopamine D2 ; Receptors, Glutamate ; Receptors, Purinergic ; Receptors, Purinergic P2X7
    Language English
    Publishing date 2020-10-07
    Publishing country Singapore
    Document type Journal Article ; Review
    ZDB-ID 2419741-5
    ISSN 1995-8218 ; 1673-7067
    ISSN (online) 1995-8218
    ISSN 1673-7067
    DOI 10.1007/s12264-020-00582-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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