Metabolic adaptation in injuries of the peripheral nervous system

The peripheral nervous system constitutes a prime example of a tissue with a strong regenerative potential.

Full recovery upon nerve trauma, however, is rare and usually fails in peripheral neuropathies - common, yet largely untreatable neurological disorders.

Nerve repair strictly depends on the orchestration of both nerve de- and regeneration by peripheral nerve glial cells, which need to overcome a substantial metabolic challenge in injury.

NervAdapt is based on the fundamental premise that Schwann cells, in the course of evolution, developed an exceptional metabolic adaptability to ensure repair.

Capitalizing on acute nerve injury as a prototypic model system to explore conserved repair mechanisms, we aim to unveil glial metabolic adaptation to increased energetic demands and distinct substrate availabilities.

A central goal of NervAdapt is to elucidate how glial homeostasis is integrated in a fine-tuned cellular network that extends to interactions with neighbouring tissue compartments.

Employing elaborated genetic mouse models, 3D electron microscopy, and leading-edge spatial and single cell to organ level profiling approaches, NervAdapt will pioneer to generate a comprehensive multi-level framework of the nerve injury response.

Chronic metabolic stressors, such as in diabetes and obesity, in turn, may lead to a constant glial overstimulation and compromise glial metabolic homeostasis.

Metabolically induced neuropathies indeed underscore the specific vulnerability of the peripheral nervous system to a systemic metabolic burden.

Within NervAdapt we follow the hypothesis that a persistently perturbed metabolic homeostasis causes molecular and cellular glial metabolic inflexibility, ultimately driving metabolic neuropathy.

Together, NervAdapt seeks to identify key checkpoints of glial metabolic (mal-)adaptation under energy demand and metabolic load, revealing a new dimension of metabolic adjustment at the nerve organ level.