Is the spinal central canal an overlooked gateway linking chronic neuroinflammation to spinal dysfunction?

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university.

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

State of the art: Chronic neuroinflammatory diseases such as multiple sclerosis (MS) are associated with spinal neuronal hyperexcitability, locomotor deficits, and autonomic dysfunctions, including impaired bladder control. While alterations of the blood–brain barrier have been extensively investigated, interfaces in direct contact with the cerebrospinal fluid (CSF) remain poorly understood, despite increasing evidence that CSF composition and signaling are altered during chronic neuroinflammation. The spinal central canal (CC) is a highly specialized CSF-parenchyma interface. It is lined by ependymal cells and surrounded by astrocytes, microglia, and CSF-contacting neurons (CSF-cNs). This microenvironment is strategically positioned to sense inflammatory and metabolic cues present in the CSF and to influence nearby spinal circuits involved in locomotor and autonomic control. Recent data indicate that experimental autoimmune encephalomyelitis (EAE), a well-established model of MS, is associated with reactive gliosis around the CC, altered CSF composition, and increased excitability of spinal neurons. However, whether chronic neuroinflammation actively remodels the CC interface, alter neuron-glia communication, and contribute to spinal dysfunction remain unknown

Objectives: We hypothesize that chronic neuroinflammation remodels the spinal CC microenvironment, disrupts neuron-glia interaction, and contributes to locomotor and autonomic dysfunction. The objective of this PhD project is to determine whether the spinal CC represents a key interface through which chronic neuroinflammation alters spinal function. Specifically, the project aims at: (i) characterizing inflammation-induced remodeling of the CC microenvironment, (ii) determining how CC remodeling affects neuronal excitability and neuroglial signaling, (iii) linking CC dysfunction to locomotor and urinary impairments. 

Methods:  The project will use the EAE mouse model and a multidisciplinary approach combining multiplex immunohistofluorescence, cell-type-specific molecular analyses, electrophysiology, two-photon calcium/voltage imaging, and behavioral assays assessing locomotion and spontaneous voiding. Analyses will be performed at defined stages of disease progression (pre-symptomatic stage, disease onset, inflammatory peak, and chronic stage). 

Expected results: This project is expected to demonstrate that chronic neuroinflammation induces a functional remodeling of the spinal CC, leading to altered neuroglial communication and neuronal excitability. These changes are anticipated to correlate with locomotor and urinary dysfunction, providing new insights into the role of CSF-spinal cord interfaces in inflammatory conditions and identifying the CC as an overlooked regulator of spinal function. 

Feasibility: All experiments will be conducted within the SpiCCI team (Spinal Cord and CSF Interface), which has strong expertise in spinal neuroglial physiology, electrophysiology, and advanced imaging. Animal experiments are covered by an approved authorization, ensuring full feasibility within a three-year PhD project. 

Within Aix Marseille Université, NeuroMarseille brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life. 

Launched in July 2018, NeuroSchool unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience. 

• Expected candidate profile : Highly motivated and curious student with a background in neuroscience/neurophysiology, cell biology, or a closely related field. Strong interest in neuroglial interactions, willingness to work with mouse models, and motivation to acquire/develop expertise in electrophysiology and imaging. The candidate should demonstrate scientific rigor, autonomy, and capability of teamwork and adaptability. English speaking, laboratory experience (e.g. cell physiology, histology, microscopy), proficient in basic IT, capability in coding (Python, Matlab, Javascript). The student will be enrolled in a supportive and caring research environment and supervision. In return, she/he is expected to fully commit to her/his research activity and PhD project.