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  1. Article ; Online: Biomarkers and treatments for mood disorders encompassing the neurosteroid and endocannabinoid systems.

    Pinna, Graziano

    Journal of neuroendocrinology

    2023  Volume 35, Issue 2, Page(s) e13226

    Abstract: Mood disorders, including major depressive disorder, postpartum depression, post-traumatic stress disorder and suicidality are highly prevalent, associated with a significant economic burden, and remain poorly diagnosed and poorly treated psychiatric ... ...

    Abstract Mood disorders, including major depressive disorder, postpartum depression, post-traumatic stress disorder and suicidality are highly prevalent, associated with a significant economic burden, and remain poorly diagnosed and poorly treated psychiatric conditions. In part, this may result from the lack of biomarkers that can guide precision medicine with individualized treatments for millions of individuals who suffer these debilitating conditions worldwide. While several biomarker candidates have been proposed for mood disorders, none has been implemented in clinical practice and the treatment still relies in the prescription of selective serotonin reuptake inhibitors that shows mixed efficacy and significant side effects. Both neurosteroid biosynthesis and the endocannabinoid system have recently provided evidence for pharmacological targets to improve mood symptoms and the neuroactive steroid allopregnanolone has recently been approved by the USA Food and Drug Administration for the treatment of post-partum depression. Clinical studies also show efficacy for the management of major depression and more studies are being conducted to study efficacy in post-traumatic stress disorder. Likewise, the endocannabinoid-like modulator, N-palmioyl ethanolamide (PEA) has shown efficacy in the treatment of major depression and bipolar disorder. While these new agents are coming forward in the field of neuropsychopharmacology as a new generation of fast-acting antidepressants, the hypothesis of whether their deficits underlying mood disorders could constitute valid predictive biomarkers to facilitate diagnosis and treatment of these conditions is under consideration.
    MeSH term(s) Female ; Humans ; Mood Disorders/diagnosis ; Mood Disorders/drug therapy ; Neurosteroids/therapeutic use ; Endocannabinoids ; Depressive Disorder, Major/diagnosis ; Depressive Disorder, Major/drug therapy ; Depression, Postpartum ; Biomarkers
    Chemical Substances Neurosteroids ; Endocannabinoids ; Biomarkers
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1007517-3
    ISSN 1365-2826 ; 0953-8194
    ISSN (online) 1365-2826
    ISSN 0953-8194
    DOI 10.1111/jne.13226
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Role of PPAR-Allopregnanolone Signaling in Behavioral and Inflammatory Gut-Brain Axis Communications.

    Pinna, Graziano

    Biological psychiatry

    2023  Volume 94, Issue 8, Page(s) 609–618

    Abstract: The gut microbiome regulates emotional behavior, stress responses, and inflammatory processes by communicating with the brain. How and which neurobiological mediators underlie this communication remain poorly understood. PPAR-α (peroxisome proliferator- ... ...

    Abstract The gut microbiome regulates emotional behavior, stress responses, and inflammatory processes by communicating with the brain. How and which neurobiological mediators underlie this communication remain poorly understood. PPAR-α (peroxisome proliferator-activated receptor α), a transcription factor susceptible to epigenetic modifications, regulates pathophysiological functions, including metabolic syndrome, inflammation, and behavior. Mood disorders, inflammatory processes, and obesity are intertwined phenomena that are associated with low blood concentrations of the anti-inflammatory and "endogenous tranquilizer" neurosteroid allopregnanolone and poor PPAR-α function. Stress and consumption of obesogenic diets repress PPAR function in brain, enterocytes, lipocytes, and immune modulatory cells favoring inflammation, lipogenesis, and mood instability. Conversely, micronutrients and modulators of PPAR-α function improve microbiome composition, dampen systemic inflammation and lipogenesis, and improve anxiety and depression. In rodent stress models of anxiety and depression, PPAR activation normalizes both PPAR-α expression downregulation and decreased allopregnanolone content and ameliorates depressive-like behavior and fear responses. PPAR-α is known to regulate metabolic and inflammatory processes activated by short-chain fatty acids; endocannabinoids and congeners, such as N-palmitoylethanolamide, drugs that treat dyslipidemias; and micronutrients, including polyunsaturated fatty acids. Both PPAR-α and allopregnanolone are abundantly expressed in the colon, and they exert potent anti-inflammatory actions by blocking the toll-like receptor-4-nuclear factor-κB pathway in peripheral immune cells, neurons, and glia. The perspective that PPAR-α regulation in the colon by gut microbiota or metabolites influences central allopregnanolone content after trafficking to the brain, thereby serving as a mediator of gut-brain axis communications, is examined in this review.
    MeSH term(s) Humans ; Pregnanolone ; Brain-Gut Axis ; Brain/metabolism ; PPAR alpha/metabolism ; Inflammation/drug therapy
    Chemical Substances Pregnanolone (BXO86P3XXW) ; PPAR alpha
    Language English
    Publishing date 2023-05-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2023.04.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Endocannabinoids and Precision Medicine for Mood Disorders and Suicide.

    Pinna, Graziano

    Frontiers in psychiatry

    2021  Volume 12, Page(s) 658433

    Language English
    Publishing date 2021-05-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2021.658433
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Allopregnanolone (1938-2019): A trajectory of 80 years of outstanding scientific achievements.

    Pinna, Graziano

    Neurobiology of stress

    2020  Volume 13, Page(s) 100246

    Language English
    Publishing date 2020-08-05
    Publishing country United States
    Document type Editorial
    ZDB-ID 2816500-7
    ISSN 2352-2895
    ISSN 2352-2895
    DOI 10.1016/j.ynstr.2020.100246
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Corrigendum: Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?

    Pinna, Graziano

    Frontiers in endocrinology

    2020  Volume 11, Page(s) 507

    Abstract: This corrects the article DOI: 10.3389/fendo.2020.00236.]. ...

    Abstract [This corrects the article DOI: 10.3389/fendo.2020.00236.].
    Language English
    Publishing date 2020-07-30
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2020.00507
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?

    Pinna, Graziano

    Frontiers in endocrinology

    2020  Volume 11, Page(s) 236

    MeSH term(s) Anesthetics/therapeutic use ; Humans ; Mood Disorders/drug therapy ; Mood Disorders/pathology ; Neurotransmitter Agents/therapeutic use ; Pregnanolone/therapeutic use ; Prognosis
    Chemical Substances Anesthetics ; Neurotransmitter Agents ; Pregnanolone (BXO86P3XXW)
    Language English
    Publishing date 2020-05-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2020.00236
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Sex and COVID-19: A Protective Role for Reproductive Steroids.

    Pinna, Graziano

    Trends in endocrinology and metabolism: TEM

    2020  Volume 32, Issue 1, Page(s) 3–6

    Abstract: Evidence shows coronavirus disease 2019 (COVID-19)-induced symptom severity and mortality is more frequent in men than in women, suggesting sex steroids may play a protective role. Female reproductive steroids, estrogen and progesterone, and its ... ...

    Abstract Evidence shows coronavirus disease 2019 (COVID-19)-induced symptom severity and mortality is more frequent in men than in women, suggesting sex steroids may play a protective role. Female reproductive steroids, estrogen and progesterone, and its metabolite allopregnanolone, are anti-inflammatory, reshape competence of immune cells, stimulate antibody production, and promote proliferation and repair of respiratory epithelial cells, suggesting they may protect against COVID-19 symptoms.
    MeSH term(s) Age Factors ; Animals ; COVID-19/immunology ; COVID-19/metabolism ; Estradiol/immunology ; Estradiol/metabolism ; Estrogens/immunology ; Estrogens/metabolism ; Female ; Humans ; Immune System/immunology ; Immune System/metabolism ; Inflammation/immunology ; Inflammation/metabolism ; Male ; Pregnanolone/immunology ; Pregnanolone/metabolism ; Pregnenolone/immunology ; Pregnenolone/metabolism ; Progesterone/immunology ; Progesterone/metabolism ; Sex Factors ; Signal Transduction/immunology
    Chemical Substances Estrogens ; Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E) ; Pregnenolone (73R90F7MQ8) ; Pregnanolone (BXO86P3XXW)
    Language English
    Publishing date 2020-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1042384-9
    ISSN 1879-3061 ; 1043-2760
    ISSN (online) 1879-3061
    ISSN 1043-2760
    DOI 10.1016/j.tem.2020.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Editorial: Role of mitochondria in post-traumatic stress disorder (PTSD).

    Pinna, Graziano / Kmita, Hanna / Lushchak, Volodymyr I

    Frontiers in physiology

    2023  Volume 14, Page(s) 1341204

    Language English
    Publishing date 2023-12-14
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1341204
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  9. Article: The Strategy of Targeting Peroxisome Proliferator-Activated Receptor (PPAR) in the Treatment of Neuropsychiatric Disorders.

    Matrisciano, Francesco / Pinna, Graziano

    Advances in experimental medicine and biology

    2023  Volume 1411, Page(s) 513–535

    Abstract: Peroxisome proliferator-activated receptors (PPARs) are nonsteroid nuclear receptors and transcription factors that regulate several neuroinflammatory and metabolic processes, recently involved in several neuropsychiatric conditions, including Alzheimer' ... ...

    Abstract Peroxisome proliferator-activated receptors (PPARs) are nonsteroid nuclear receptors and transcription factors that regulate several neuroinflammatory and metabolic processes, recently involved in several neuropsychiatric conditions, including Alzheimer's disease, Parkinson's disease, major depressive disorder, post-traumatic stress disorder (PTSD), schizophrenia spectrum disorders, and autism spectrum disorders. PPARs are ligand-activated receptors that, following stimulation, induce neuroprotective effects by decreasing neuroinflammatory processes through inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) expression and consequent suppression of pro-inflammatory cytokine production. PPARs heterodimerize with the retinoid X-receptor (RXR) and bind to PPAR-responsive regulatory elements (PPRE) in the promoter region of target genes involved in lipid metabolism, synthesis of cholesterol, catabolism of amino acids, and inflammation. Interestingly, PPARs are considered functionally part of the extended endocannabinoid (eCB) system that includes the classic eCB, anandamide, which act at cannabinoid receptor types 1 (CB1) and 2 (CB2) and are implicated in the pathophysiology of stress-related neuropsychiatric disorders. In preclinical studies, PPAR stimulation improves anxiety and depression-like behaviors by enhancing neurosteroid biosynthesis. The peculiar functional role of PPARs by exerting anti-inflammatory and neuroprotective effects and their expression localization in neurons and glial cells of corticolimbic circuits make them particularly interesting as novel therapeutic targets for several neuropsychiatric disorders characterized by underlying neuroinflammatory/neurodegenerative mechanisms. Herein, we discuss the pathological hallmarks of neuropsychiatric conditions associated with neuroinflammation, as well as the pivotal role of PPARs with a special emphasis on the subtype alpha (PPAR-α) as a suitable molecular target for therapeutic interventions.
    MeSH term(s) Humans ; Peroxisome Proliferator-Activated Receptors ; Depressive Disorder, Major ; Neuroprotective Agents ; Transcription Factors/metabolism ; Receptors, Cytoplasmic and Nuclear
    Chemical Substances Peroxisome Proliferator-Activated Receptors ; Neuroprotective Agents ; Transcription Factors ; Receptors, Cytoplasmic and Nuclear
    Language English
    Publishing date 2023-03-22
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-19-7376-5_22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Biomarkers for PTSD at the Interface of the Endocannabinoid and Neurosteroid Axis.

    Pinna, Graziano

    Frontiers in neuroscience

    2018  Volume 12, Page(s) 482

    Language English
    Publishing date 2018-08-06
    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.2018.00482
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