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  1. Article ; Online: Type 2 and Non-type 2 Inflammation in the Upper Airways: Cellular and Molecular Alterations in Olfactory Neuroepithelium Cell Populations.

    Marin, Concepció / Alobid, Isam / López-Chacón, Mauricio / VanStrahlen, Camilo R / Mullol, Joaquim

    Current allergy and asthma reports

    2024  Volume 24, Issue 4, Page(s) 211–219

    Abstract: Purpose of review: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this ... ...

    Abstract Purpose of review: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases.
    Recent findings: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery.
    MeSH term(s) Humans ; Smell/physiology ; Anosmia/metabolism ; Inflammation/metabolism ; Olfactory Mucosa/metabolism ; Sinusitis ; Olfaction Disorders ; Chronic Disease ; Rhinitis
    Language English
    Publishing date 2024-03-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057370-4
    ISSN 1534-6315 ; 1529-7322
    ISSN (online) 1534-6315
    ISSN 1529-7322
    DOI 10.1007/s11882-024-01137-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Chronic Rhinosinusitis and COVID-19.

    Marin, Concepció / Hummel, Thomas / Liu, Zheng / Mullol, Joaquim

    The journal of allergy and clinical immunology. In practice

    2022  Volume 10, Issue 6, Page(s) 1423–1432

    Abstract: The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of ...

    Abstract The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non-type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19.
    MeSH term(s) Anosmia ; COVID-19 ; Chronic Disease ; Humans ; Nasal Polyps/complications ; Nasal Polyps/epidemiology ; Nasal Polyps/therapy ; Olfaction Disorders/epidemiology ; Pandemics ; Rhinitis/epidemiology ; Rhinitis/etiology ; Rhinitis/therapy ; Sinusitis/epidemiology ; Sinusitis/etiology ; Sinusitis/therapy
    Language English
    Publishing date 2022-03-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2022.03.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Olfactory Dysfunction in Mental Illness.

    Marin, Concepció / Alobid, Isam / Fuentes, Mireya / López-Chacón, Mauricio / Mullol, Joaquim

    Current allergy and asthma reports

    2023  Volume 23, Issue 3, Page(s) 153–164

    Abstract: Purpose of review: Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, ... ...

    Abstract Purpose of review: Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, hitherto underestimated, that the olfactory pathways play in the regulation of higher brain functions and its involvement in the pathophysiology of psychiatric disorders, as well as the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in psychiatric conditions.
    Recent findings: The olfactory deficits present in anxiety, depression, schizophrenia or bipolar disorder consist of specific alterations of different components of the sense of smell, mainly the identification of odours, as well as the qualifications of their hedonic valence (pleasant or unpleasant). Epidemiological findings have shown that both environmental factors, such as air pollutants, and inflammatory disease of the upper respiratory tract, can contribute to an increased risk of mental illness, at least in part, due to peripheral inflammatory mechanisms of the olfactory system. In this review, we describe the neurobiology of olfaction, and the most common olfactory function alterations in several psychiatric conditions and its role as a useful symptom for the differential diagnosis. We also highlight the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in these psychiatric conditions.
    MeSH term(s) Humans ; Smell/physiology ; Mental Disorders ; Olfaction Disorders ; Emotions/physiology ; Inflammation
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057370-4
    ISSN 1534-6315 ; 1529-7322
    ISSN (online) 1534-6315
    ISSN 1529-7322
    DOI 10.1007/s11882-023-01068-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Globus pallidus, but not entopeduncular nucleus, 6-OHDA-induced lesion attenuates L-Dopa-induced dyskinesia in the rat model of Parkinson's disease.

    Marin, Concepció / Bonastre, Mercè / Fuentes, Mireya / Mullol, Joaquim

    Pharmacology, biochemistry, and behavior

    2020  Volume 197, Page(s) 173013

    Abstract: Although extrastriatal dopaminergic (DAergic) systems are being recognized as contributors to Parkinson's disease (PD) pathophysiology, the role of extrastriatal DA depletion in L-Dopa-induced dyskinesia (LID) is still unknown. In view of the physiologic ...

    Abstract Although extrastriatal dopaminergic (DAergic) systems are being recognized as contributors to Parkinson's disease (PD) pathophysiology, the role of extrastriatal DA depletion in L-Dopa-induced dyskinesia (LID) is still unknown. In view of the physiologic actions of DA on pallidal neuronal activity and the effects on motor behavior of local injection of DA drugs, the loss of the external (GPe, GP in rodents) and internal (GPi, entopeduncular nucleus (EP) in rodents) pallidal DAergic innervation might differentially contribute to LID. A role of pallidal serotonergic (SER) terminals in LID has been highlighted, however, the effect of DAergic innervation is unknown. We investigated the role of DAergic pallidal depletion on LID. Rats were distributed in groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the GP, or EP, and in the medial forebrain bundle (MFB) as follows: a) MFB-sham+GP-sham, b) MFB-sham+GP-lesion, c) MFB-lesion+GP-sham, d) MFB-lesion+GP-lesion, e) MFB-sham+EP-sham, f) MFB-sham+EP-lesion, g) MFB-lesion+EP-sham, and h) MFB-lesion+EP-lesion. Four weeks later, animals were treated with L-Dopa (6 mg/kg) twice daily for 22 days.. Immunohistochemical studies were performed in order to investigate the changes in pallidal SER and serotonin transporter (SERT) levels. GP, but not EP, DAergic denervation attenuated LID in rats with a concomitant MFB lesion (p < 0.01). No differences were found in GP SERT expression between groups of animals developing or not LID. These results provide evidence of the relevance of GP DAergic innervation in LID. The conversion of levodopa to DA in GP serotonergic nerve fibers appears not to be the major mechanism underlying LID.
    MeSH term(s) Animals ; Disease Models, Animal ; Dopamine/metabolism ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/metabolism ; Dyskinesia, Drug-Induced/etiology ; Entopeduncular Nucleus/drug effects ; Entopeduncular Nucleus/metabolism ; Entopeduncular Nucleus/physiopathology ; Globus Pallidus/drug effects ; Globus Pallidus/metabolism ; Globus Pallidus/physiopathology ; Levodopa/administration & dosage ; Levodopa/adverse effects ; Male ; Medial Forebrain Bundle/drug effects ; Medial Forebrain Bundle/metabolism ; Medial Forebrain Bundle/physiopathology ; Oxidopamine/administration & dosage ; Oxidopamine/pharmacology ; Parkinson Disease, Secondary/chemically induced ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Signal Transduction/drug effects
    Chemical Substances Serotonin Plasma Membrane Transport Proteins ; Slc6a4 protein, rat ; Serotonin (333DO1RDJY) ; Levodopa (46627O600J) ; Oxidopamine (8HW4YBZ748) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2020-08-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2020.173013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Olfactory Dysfunction in Traumatic Brain Injury: the Role of Neurogenesis.

    Marin, Concepció / Langdon, Cristóbal / Alobid, Isam / Mullol, Joaquim

    Current allergy and asthma reports

    2020  Volume 20, Issue 10, Page(s) 55

    Abstract: Purpose of review: Olfactory functioning disturbances are common following traumatic brain injury (TBI) having a significant impact on quality of life. A spontaneous recovery of the olfactory function over time may occur in TBI patients. Although there ... ...

    Abstract Purpose of review: Olfactory functioning disturbances are common following traumatic brain injury (TBI) having a significant impact on quality of life. A spontaneous recovery of the olfactory function over time may occur in TBI patients. Although there is no standard treatment for patients with posttraumatic olfactory loss, olfactory training (OT) has shown some promise beneficial effects. However, the mechanisms underlying spontaneous recovery and olfactory improvement induced by OT are not completely known.
    Recent findings: The spontaneous recovery of the olfactory function and the improvement of olfactory function after OT have recently been associated with an increase in subventricular (SVZ) neurogenesis and an increase in olfactory bulb (OB) glomerular dopaminergic (DAergic) interneurons. In addition, after OT, an increase in electrophysiological responses at the olfactory epithelium (OE) level has been reported, indicating that recovery of olfactory function not only affects olfactory processing at the central level, but also at peripheral level. However, the role of OE stem cells in the spontaneous recovery and in the improvement of olfactory function after OT in TBI is still unknown. In this review, we describe the physiology of the olfactory system, and the olfactory dysfunction after TBI. We highlight the possible role for the SVZ neurogenesis and DAergic OB interneurons in the recovery of the olfactory function. In addition, we point out the relevance of the OE neurogenesis process as a future target for the research in the pathophysiological mechanisms involved in the olfactory dysfunction in TBI. The potential of basal stem cells as a promising candidate for replacement therapies is also described.
    MeSH term(s) Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/physiopathology ; Humans ; Neurogenesis/physiology ; Olfaction Disorders/physiopathology ; Quality of Life/psychology
    Language English
    Publishing date 2020-07-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057370-4
    ISSN 1534-6315 ; 1529-7322
    ISSN (online) 1534-6315
    ISSN 1529-7322
    DOI 10.1007/s11882-020-00949-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Lack of correlation between dyskinesia and pallidal serotonin transporter expression-induced by L-Dopa and Pramipexole in hemiparkinsonian rats.

    Marin, Concepció / Bonastre, Mercè / Fuentes, Mireya / Mullol, Joaquim

    Pharmacology, biochemistry, and behavior

    2020  Volume 197, Page(s) 173012

    Abstract: The role of pallidal serotonergic terminals in the development of L-Dopa-induced dyskinesias (LIDs) in Parkinson's disease (PD) has been recently highlighted correlating pallidal serotonin transporter (SERT) expression levels with dyskinesias severity. ... ...

    Abstract The role of pallidal serotonergic terminals in the development of L-Dopa-induced dyskinesias (LIDs) in Parkinson's disease (PD) has been recently highlighted correlating pallidal serotonin transporter (SERT) expression levels with dyskinesias severity. However, the role of external globus pallidus (GPe, GP in rodents) serotonergic function in LIDs is still controversial since several studies have shown no differences in GPe serotonin (SER) and SERT levels between dyskinetic and non-dyskinetic PD patients. In addition, the increase in pallidal SERT/dopamine transporter (DAT) binding ratio obtained in positron emission tomography studies has been shown similar in both subtypes of PD patients. Based on these controversial results, further studies are required to clarify the possible involvement of GPe serotonergic activity in LIDs expression. We investigated the pallidal SER and SERT expression changes and the abnormal involuntary movements (AIMs) induced by L-Dopa or the D3/D2 dopamine (DA) agonist, Pramipexole, in partial unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. L-Dopa treatment led to an increment of axial (p < 0.01), limb (p < 0.01), and orolingual (p < 0.01) AIMs. However, Pramipexole treatment did not induce AIMs. The number of GP SERT-positive axon varicosities was increased in L-Dopa (p < 0.05) and Pramipexole (p < 0.01) treated rats. No differences were observed in the number of GP SERT-positive varicosities between L-Dopa and Pramipexole treatments. Our results indicate a lack of correlation between GP SERT expression levels and the development of AIMs suggesting that pallidal serotonergic fibers are not responsible for LIDs. The possible involvement of the SER system in dyskinesia may include other mechanisms.
    MeSH term(s) Animals ; Disease Models, Animal ; Dopamine Agonists/adverse effects ; Dyskinesia, Drug-Induced/etiology ; Dyskinesia, Drug-Induced/metabolism ; Globus Pallidus/metabolism ; Levodopa/adverse effects ; Male ; Oxidopamine/pharmacology ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/metabolism ; Pramipexole/adverse effects ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Signal Transduction/drug effects
    Chemical Substances Dopamine Agonists ; Serotonin Plasma Membrane Transport Proteins ; Slc6a4 protein, rat ; Serotonin (333DO1RDJY) ; Levodopa (46627O600J) ; Pramipexole (83619PEU5T) ; Oxidopamine (8HW4YBZ748)
    Language English
    Publishing date 2020-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2020.173012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Olfactory Bulb Excitotoxicity as a Gap-Filling Mechanism Underlying the Link Between Traumatic Brain Injury-Induced Secondary Neuronal Degeneration and Parkinson's Disease-Like Pathology.

    Marin, Concepció / Fuentes, Mireya / Alobid, Isam / Tubita, Valeria / Rojas-Lechuga, María Jesús / Mullol, Joaquim

    Neurochemical research

    2022  Volume 47, Issue 4, Page(s) 1025–1036

    Abstract: There is increasing preclinical and clinical data supporting a potential association between Traumatic Brain Injury (TBI) and Parkinson's disease (PD). It has been suggested that the glutamate-induced excitotoxicity underlying TBI secondary neuronal ... ...

    Abstract There is increasing preclinical and clinical data supporting a potential association between Traumatic Brain Injury (TBI) and Parkinson's disease (PD). It has been suggested that the glutamate-induced excitotoxicity underlying TBI secondary neuronal degeneration (SND) might be associated with further development of PD. Interestingly, an accumulation of extracellular glutamate and olfactory dysfunction are both sharing pathological conditions in TBI and PD. The possible involvement of glutamate excitotoxicity in olfactory dysfunction has been recently described, however, the role of olfactory bulbs (OB) glutamate excitotoxicity as a possible mechanism involved in the association between TBI and PD-related neurodegeneration has not been investigated yet. We examined the number of nigral dopaminergic neurons (TH +), nigral α-synuclein expression, the striatal dopamine transporter (DAT) expression, and motor performance after bilateral OB N-Methyl-D-Aspartate (NMDA)-induced excitotoxic lesions in rodents. Bulbar NMDA administration induced a decrease in the number of correct choices in the discrimination tests one week after lesions (p < 0.01) and a significant decrease in the number of nigral DAergic neurons (p < 0.01) associated with an increase in α-synuclein expression (p < 0.01). No significant striatal changes in DAT expression or motor alterations were observed. Our results show an association between TBI-induced SND and PD-related neurodegeneration suggesting that the OB excitotoxicity occurring in TBI SND may be a filling gap mechanism underlying the link between TBI and PD-like pathology.
    MeSH term(s) Animals ; Brain Injuries, Traumatic/metabolism ; Disease Models, Animal ; Dopaminergic Neurons/metabolism ; Humans ; Olfactory Bulb/metabolism ; Parkinson Disease/metabolism ; Substantia Nigra/metabolism ; alpha-Synuclein/metabolism
    Chemical Substances alpha-Synuclein
    Language English
    Publishing date 2022-01-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-021-03503-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Reply.

    Mullol, Joaquim / Mariño, Franklin / Valls, Meritxell / Alobid, Isam / Marin, Concepció

    The Journal of allergy and clinical immunology

    2020  Volume 146, Issue 2, Page(s) 463–464

    MeSH term(s) Chronic Disease ; Humans ; Smell
    Keywords covid19
    Language English
    Publishing date 2020-06-24
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2020.04.048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The sense of smell in chronic rhinosinusitis.

    Mullol, Joaquim / Mariño-Sánchez, Franklin / Valls, Meritxell / Alobid, Isam / Marin, Concepció

    The Journal of allergy and clinical immunology

    2020  Volume 145, Issue 3, Page(s) 773–776

    MeSH term(s) Chronic Disease ; Humans ; Nasal Polyps/complications ; Olfaction Disorders/epidemiology ; Olfaction Disorders/etiology ; Prevalence ; Rhinitis/complications ; Sinusitis/complications
    Language English
    Publishing date 2020-03-30
    Publishing country United States
    Document type Editorial ; Review
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2020.01.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: ACE2 downregulation in olfactory mucosa: Eosinophilic rhinosinusitis as COVID-19 protective factor?

    Marin, Concepció / Tubita, Valeria / Langdon, Cristóbal / Fuentes, Mireya / Rojas-Lechuga, María Jesús / Valero, Antonio / Alobid, Isam / Mullol, Joaquim

    Allergy

    2021  Volume 76, Issue 9, Page(s) 2904–2907

    MeSH term(s) COVID-19 ; Down-Regulation ; Humans ; Olfactory Mucosa/metabolism ; Peptidyl-Dipeptidase A/metabolism ; Protective Factors ; SARS-CoV-2
    Chemical Substances Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2021-05-28
    Publishing country Denmark
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.14904
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