Actomyosin-II protects axons from degeneration induced by mild mechanical stress.

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.

Intrinsic heterogeneity in axon regeneration.

The nervous system is composed of a variety of neurons and glial cells with different morphology and functions. In the mammalian peripheral nervous system (PNS) or the lower vertebrate central nervous system (CNS), most neurons can regenerate extensively after axotomy, while the neurons in the mammalian CNS possess only limited regenerative ability. This heterogeneity is common within and across species. The studies about the transcriptomes after nerve injury in different animal models have revealed a series of molecular and cellular events that occurred in neurons after axotomy. However, responses of various types of neurons located in different positions of individuals were different remarkably. Thus, researchers aim to find the key factors that are conducive to regeneration, so as to provide the molecular basis for solving the regeneration difficulties after CNS injury. Here we review the heterogeneity of axonal regeneration among different cell subtypes in different animal models or the same organ, emphasizing the importance of comparative studies within and across species.

Emerging neurotropic features of SARS-CoV-2.

The prevailing coronavirus disease-19 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has presented some neurological manifestations including hyposmia, hypogeusia, headache, stroke, encephalitis, Guillain-Barre syndrome, and some neuropsychiatric disorders. Although several cell types in the brain express angiotensin-converting enzyme-2 (ACE2), the main SARS-CoV-2 receptor, and other related proteins, it remains unclear whether the observed neurological manifestations are attributed to virus invasion into the brain or just comorbidities caused by dysregulation of systemic factors. Here, we briefly review the neurological manifestations of SARS-CoV-2, summarize recent evidence for the potential neurotropism of SARS-CoV-2, and discuss the potential mechanisms of COVID-19-associated neurological diseases.