Gut-brain axis: misalignment in glymphatic system functionality as a driver of neurodegeneration in DSS-driven colitis model

Gut-brain axis: misalignment in glymphatic system functionality as a driver of neurodegeneration in DSS-driven colitis model

Research group: Cristina Lanni

The research project is based on understanding the link between gut and brain in the etiopathogenesis of neurodegenerative disorders. In particular, by using animal models of colitis, our research aims to investigate the hypothesis that a peripheral gut inflammation may induce a misalignment of the circadian clockwork, thus affecting the glymphatic system and triggering early signs of neurodegeneration.
The research aims:
1) to detail the impact of colonic inflammation on the circadian clock machinery in colon and different brain areas using single nuclei RNA sequencing (snRNAseq). We aim to deepen the molecular and cellular signatures induced by a peripheral inflammatory hit and its impact on cellular networks (named interactome).
2) to monitor GS dynamics in the brain using in vivo magnetic resonance (MRI) imaging, and to analyze the relative concentrations of a priori selected by MR spectroscopy (MRS).
3) to address synaptic/neuronal function by in vitro functional assays examining dynamic neurotransmitter release.
4) to investigate the deposition of waste products and potential changes in CSF composition by proteomic analysis.

Recent Publications:

  • Fagiani F, Baronchelli E, Pittaluga A, Pedrini E, Scacchi C, Govoni S, Lanni C. The Circadian Molecular Machinery in CNS Cells: A Fine Tuner of Neuronal and Glial Activity With Space/Time Resolution. Front Mol Neurosci. 2022 Jul 1;15:937174. doi: 10.3389/fnmol.2022.937174. PMID: 35845604.
  • Fagiani F, Di Marino D, Romagnoli A, Travelli C, Voltan D, Di Cesare Mannelli L, Racchi M, Govoni S, Lanni C. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct Target Ther. 2022 Feb 8;7(1):41. doi: 10.1038/s41392-022-00899-y. PMID: 35136018.