Immune system alterations have been implicated in various dopamine-related disorders, such as schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder (ADHD). How immunity might be influenced by dopaminergic dysfunction and impact on clinically-relevant behaviors is still uncertain. We performed a peripheral and cerebral immunophenotyping in mice bearing dopaminergic alteration produced by genetic liability (hypofunction of the dopamine transporter DAT) and psychostimulant (amphetamine) administration. We found that DAT hypofunction influences immune tolerance by increasing functional Tregs and adrenomedullin levels in the thymus and spleen, while reducing microglia activation and infiltration of brain monocyte-derived macrophages (mo-MΦ). Remarkably, both DAT hypofunction and amphetamine treatment are associated with a weaker activation of the choroid plexus (CP) gateway. Conversely, amphetamine reactivated the CP in the setting of DAT hypofunction, paralleling its paradoxical ADHD-relevant behavioral effects. These findings add new knowledge on dopaminergic immunopharmacology and support the immunomodulation of CP functionality as a promising therapeutic strategy for neurodevelopmental and psychiatric disorders.

Dopamine–mediated immunomodulation affects choroid plexus function / Castellani, G.; Contarini, G.; Mereu, M.; Albanesi, E.; Devroye, C.; D'Amore, C.; Ferretti, V.; De Martin, S.; Papaleo, F.. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 81:(2019), pp. 138-150. [10.1016/j.bbi.2019.06.006]

Dopamine–mediated immunomodulation affects choroid plexus function

Ferretti V.;
2019

Abstract

Immune system alterations have been implicated in various dopamine-related disorders, such as schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder (ADHD). How immunity might be influenced by dopaminergic dysfunction and impact on clinically-relevant behaviors is still uncertain. We performed a peripheral and cerebral immunophenotyping in mice bearing dopaminergic alteration produced by genetic liability (hypofunction of the dopamine transporter DAT) and psychostimulant (amphetamine) administration. We found that DAT hypofunction influences immune tolerance by increasing functional Tregs and adrenomedullin levels in the thymus and spleen, while reducing microglia activation and infiltration of brain monocyte-derived macrophages (mo-MΦ). Remarkably, both DAT hypofunction and amphetamine treatment are associated with a weaker activation of the choroid plexus (CP) gateway. Conversely, amphetamine reactivated the CP in the setting of DAT hypofunction, paralleling its paradoxical ADHD-relevant behavioral effects. These findings add new knowledge on dopaminergic immunopharmacology and support the immunomodulation of CP functionality as a promising therapeutic strategy for neurodevelopmental and psychiatric disorders.
2019
ADHD; Amphetamine; DAT; Macrophages; Microglia; Peripheral and CNS immune crosstalk
01 Pubblicazione su rivista::01a Articolo in rivista
Dopamine–mediated immunomodulation affects choroid plexus function / Castellani, G.; Contarini, G.; Mereu, M.; Albanesi, E.; Devroye, C.; D'Amore, C.; Ferretti, V.; De Martin, S.; Papaleo, F.. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 81:(2019), pp. 138-150. [10.1016/j.bbi.2019.06.006]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1415982
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