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The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.

ABSTRACT: The central nervous system (CNS) is finely protected by the blood-brain barrier (BBB). Immune soluble factors such as cytokines (CKs) are normally produced in the CNS, contributing to physiological immunosurveillance and homeostatic synaptic scaling. CKs are peptide, pleiotropic molecules involved in a broad range of cellular functions, with a pivotal role in resolving the inflammation and promoting tissue healing. However, pro-inflammatory CKs can exert a detrimental effect in pathological conditions, spreading the damage. In the inflamed CNS, CKs recruit immune cells, stimulate the local production of other inflammatory mediators, and promote synaptic dysfunction. Our understanding of neuroinflammation in humans owes much to the study of multiple sclerosis (MS), the most common autoimmune and demyelinating disease, in which autoreactive T cells migrate from the periphery to the CNS after the encounter with a still unknown antigen. CNS-infiltrating T cells produce pro-inflammatory CKs that aggravate local demyelination and neurodegeneration. This review aims to recapitulate the state of the art about CKs role in the healthy and inflamed CNS, with focus on recent advances bridging the study of adaptive immune system and neurophysiology.

SUBMITTER: Amoriello R

PROVIDER: S-EPMC10807071 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.

Amoriello Roberta R Memo Christian C Ballerini Laura L Ballerini Clara C

Molecular brain 20240123 1

The central nervous system (CNS) is finely protected by the blood-brain barrier (BBB). Immune soluble factors such as cytokines (CKs) are normally produced in the CNS, contributing to physiological immunosurveillance and homeostatic synaptic scaling. CKs are peptide, pleiotropic molecules involved in a broad range of cellular functions, with a pivotal role in resolving the inflammation and promoting tissue healing. However, pro-inflammatory CKs can exert a detrimental effect in pathological cond ...[more]

PMID: 38263055

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Project description:BackgroundDepression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [(18)F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.MethodsThe Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [(18)F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [(18)F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [(18)F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [(18)F]PBR111 distribution volume ratio.ConclusionsOur results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally.

Dataset Information

The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.

Publications

The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.

Similar Datasets

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