暂无摘要。

According to the World Health Organization, about one-third of the population experiences insomnia symptoms, and about 10-15% suffer from chronic insomnia, the most common sleep disorder. Sleeping difficulties associated with insomnia are often linked to chronic sleep deprivation, which has a negative health impact partly due to disruption in the internal synchronisation of biological clocks. These are regulated by clock genes and modulate most biological processes. Most studies addressing circadian rhythm regulation have focused on the role of neurons, yet glial cells also impact circadian rhythms and sleep regulation. Chronic insomnia and sleep loss have been associated with glial cell activation, exacerbated neuroinflammation, oxidative stress, altered neuronal metabolism and synaptic plasticity, accelerated age-related processes and decreased lifespan. It is, therefore, essential to highlight the importance of glia-neuron interplay on sleep/circadian regulation and overall healthy brain function. Hence, in this review, we aim to address the main neurobiological mechanisms involved in neuron-glia crosstalk, with an emphasis on microglia and astrocytes, in both healthy sleep, chronic sleep deprivation and chronic insomnia.

Parkinson\'s disease (PD) is a progressive neurodegenerative disorder. The classical behavioral defects of PD patients involve motor symptoms such as bradykinesia, tremor, and rigidity, as well as non-motor symptoms such as anosmia, depression, and cognitive impairment. Pathologically, the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the accumulation of α-synuclein (α-syn)-composed Lewy bodies (LBs) and Lewy neurites (LNs) are key hallmarks. Glia are more than mere bystanders that simply support neurons, they actively contribute to almost every aspect of neuronal development and function; glial dysregulation has been implicated in a series of neurodegenerative diseases including PD. Importantly, amounting evidence has added glial activation and neuroinflammation as new features of PD onset and progression. Thus, gaining a better understanding of glia, especially neuron-glia crosstalk, will not only provide insight into brain physiology events but also advance our knowledge of PD pathologies. This review addresses the current understanding of α-syn pathogenesis in PD, with a focus on neuron-glia crosstalk. Particularly, the transmission of α-syn between neurons and glia, α-syn-induced glial activation, and feedbacks of glial activation on DA neuron degeneration are thoroughly discussed. In addition, α-syn aggregation, iron deposition, and glial activation in regulating DA neuron ferroptosis in PD are covered. Lastly, we summarize the preclinical and clinical therapies, especially targeting glia, in PD treatments.

Neuronal remodeling is a conserved mechanism that eliminates unwanted neurites and can include the loss of cell bodies. In these processes, a key role for glial cells in events from synaptic pruning to neuron elimination has been clearly identified in the last decades. Signals sent from dying neurons or neurites to be removed are received by appropriate glial cells. After receiving these signals, glial cells infiltrate degenerating sites and then, engulf and clear neuronal debris through phagocytic mechanisms. There are few identified or proposed signals and receptors involved in neuron-glia crosstalk, which induces the transformation of glial cells to phagocytes during neuronal remodeling in Drosophila. Many of these signaling pathways are conserved in mammals. Here, we particularly emphasize the role of Orion, a recently identified neuronal CX3 C chemokine-like secreted protein, which induces astrocyte infiltration and engulfment during mushroom body neuronal remodeling. Although, chemokine signaling was not described previously in insects we propose that chemokine-like involvement in neuron/glial cell interaction is an evolutionarily ancient mechanism.

Cytotoxicity and consequent cell death pathways are a critical component of the immune response to infection, disease or injury. While numerous examples of inflammation causing neuronal sensitization and pain have been described, there is a growing appreciation of the role of cytotoxic immunity in response to painful nerve injury. In this review we highlight the functions of cytotoxic immune effector cells, focusing in particular on natural killer (NK) cells, and describe the consequent action of these cells in the injured nerve as well as other chronic pain conditions and peripheral neuropathies. We describe how targeted delivery of cytotoxic factors via the immune synapse operates alongside Wallerian degeneration to allow local axon degeneration in the absence of cell death and is well-placed to support the restoration of homeostasis within the nerve. We also summarize the evidence for the expression of endogenous ligands and receptors on injured nerve targets and infiltrating immune cells that facilitate direct neuro-immune interactions, as well as modulation of the surrounding immune milieu. A number of chronic pain and peripheral neuropathies appear comorbid with a loss of function of cellular cytotoxicity suggesting such mechanisms may actually help to resolve neuropathic pain. Thus while the immune response to peripheral nerve injury is a major driver of maladaptive pain, it is simultaneously capable of directing resolution of injury in part through the pathways of cellular cytotoxicity. Our growing knowledge in tuning immune function away from inflammation toward recovery from nerve injury therefore holds promise for interventions aimed at preventing the transition from acute to chronic pain.

暂无摘要。