Mechanical Signaling in the Normal Brain and in Neurological and Neurodegenerative Disorders

The response of the mammalian brain to internally generated mechanical forces is a new field of neuroscience that is as unexplored as it is fascinating. For example, recent studies indicate that several molecular mechanotransducers are expressed in central neurons and glial cells. In particular, mechanically-gated ion channels expressed in neocortical and hippocampal neurons have been shown to exert surprisingly powerful influences on neuronal activities, matching even those influences exerted by voltage- and synaptic transmitter-gated channels. Yet, the functional significance of any mechanical signalling in the normal brain remains poorly understood. Similarly, the role different intrinsic mechanical forces play in activating specific mechanical signaling pathways has been little explored.

In contrast, the effects of extrinsic or abnormal mechanical forces on brain function have been long recognized as critical in the pathophysiology of symptoms due to traumatic brain injury (TBI) and normal pressure hydrocephalus (NPH), although the mechanisms remain essentially unknown. Moreover, both these conditions have been associated with irreversible neurodegenerative diseases, most notably Alzheimer's disease (AD), highlighting an interesting connection between mechanical stress and neurodegenearation. Finally, a novel horizon in therapeutic neuromodulation of neurological diseases includes mechanical stimulation, delivered by either wearable or structured sources, in different modalities.

The aim of this Research Topic is to explore these various issues, including the nature and expression of molecular mechanotransducers in the brain, the identification of intrinsic and extrinsic mechanical forces that may activate mechanical signalling, and the consequences of this signalling on normal and abnormal brain function. In addition, studies addressing either the causative role or the therapeutic effects of mechanical stimulation in patients and models of neurological diseases, specifically neurodegenerative disorders will be addressed.