ID: 464503
Short Link: https://gregory-ms.com/articles/464503/
Discovery Date: 11 June 2022, 15:41:25 UTC
Published Date: 2022-06-10 23:00:00
Source: BioMedCentral
Link: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-022-02512-z
Manual Selection: true
Machine Learning Gaussian Naive Bayes Model: false
Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system . Trimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration . Adoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice .
jats:titleAbstract</jats:title> jats:pjats:boldBackground</jats:bold>Trimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration. Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system (CNS), but their activities are impaired in neurodegenerative diseases. In this study, we aimed to determine whether adoptive transfer of Tregs, as a living drug, ameliorates hippocampal neurodegeneration in TMT-intoxicated mice.jats:boldMethods</jats:bold>CD4jats:sup+</jats:sup>CD25jats:sup+</jats:sup> Tregs were expandedjats:italic in vitro</jats:italic> and adoptively transferred to TMT-treated mice. First, we explored the effects of Tregs on behavioral deficits using the Morris water maze and elevated plus maze tests. Biomarkers related to memory formation, such as cAMP response element-binding protein (CREB), protein kinase C (PKC), neuronal nuclear protein (NeuN), nerve growth factor (NGF), and ionized calcium binding adaptor molecule 1 (Iba1) in the hippocampus were examined by immunohistochemistry after mouse sacrifice. To investigate the neuroinflammatory responses, the polarization status of microglia was examined jats:italicin vivo</jats:italic> and jats:italicin vitro </jats:italic>using real-time reverse transcription polymerase chain reaction (rtPCR) and Enzyme-linked immunosorbent assy (ELISA). Additionally, the inhibitory effects of Tregs on TMT-induced microglial activation were examined using time-lapse live imaging jats:italicin vitro </jats:italic>with an activation-specific fluorescence probe, CDr20.jats:boldResults</jats:bold>Adoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice. Additionally, adoptive transfer of Tregs reduced neuronal loss and recovered the expression of neurogenesis enhancing molecules in the hippocampi of TMT-intoxicated mice. In particular, Tregs inhibited microglial activation and pro-inflammatory cytokine release in the hippocampi of TMT-intoxicated mice. The inhibitory effects of TMT were also confirmed via jats:italicin vitro </jats:italic>live time lapse imaging in a Treg/microglia co-culture system.jats:boldConclusions</jats:bold>These data suggest that adoptive transfer of Tregs ameliorates disease progression in TMT-induced neurodegeneration by promoting neurogenesis and modulating microglial activation and polarization.</jats:p>