Neuroglia (Basel, Switzerland)最新文献

Humans with post-traumatic stress disorder (PTSD) exhibit sleep disturbances that include insomnia, nightmares, and enhanced daytime sleepiness. Sleep disturbances are considered a hallmark feature of PTSD; however, little is known about the cellular and molecular mechanisms regulating trauma-induced sleep disorders. Using a rodent model of PTSD called "Single Prolonged Stress" (SPS) we examined the requirement of the brain-type fatty acid binding protein Fabp7, an astrocyte expressed lipid-signaling molecule, in mediating trauma-induced sleep disturbances. We measured baseline sleep/wake parameters and then exposed Fabp7 knock-out (KO) and wild-type (WT) C57BL/6N genetic background control animals to SPS. Sleep and wake measurements were obtained immediately following the initial trauma exposure of SPS, and again 7 days later. We found that active-phase (dark period) wakefulness was similar in KO and WT at baseline and immediately following SPS; however, it was significantly increased after 7 days. These effects were opposite in the inactive-phase (light period), where KOs exhibited increased wake in baseline and following SPS, but returned to WT levels after 7 days. To examine the effects of Fabp7 on unconditioned anxiety following trauma, we exposed KO and WT mice to the light-dark box test before and after SPS. Prior to SPS, KO and WT mice spent similar amounts of time in the lit compartment. Following SPS, KO mice spent significantly more time in the lit compartment compared to WT mice. These results demonstrate that mutations in an astrocyte-expressed gene (Fabp7) influence changes in stress-dependent sleep disturbances and associated anxiety behavior.

Neural precursor cells (NPCs) are generated in the subventricular zone (SVZ) and travel through the rostral migratory stream (RMS) to replace olfactory bulb interneurons in the brains of most adult mammals. Following brain injury, SVZ-derived NPCs can divert from the RMS and migrate toward injured brain regions but arrive in numbers too low to promote functional recovery without experimental intervention. Our lab has biofabricated a "living scaffold" that replicates the structural and functional features of the endogenous RMS. This tissue-engineered rostral migratory stream (TE-RMS) is a new regenerative medicine strategy designed to facilitate stable and sustained NPC delivery into neuron-deficient brain regions following brain injury or neurodegenerative disease and an in vitro tool to investigate the mechanisms of neuronal migration and cell-cell communication. We have previously shown that the TE-RMS replicates the basic structure and protein expression of the endogenous RMS and can direct immature neuronal migration in vitro and in vivo. Here, we further describe profound morphological changes that occur following precise physical manipulation and subsequent self-assembly of astrocytes into the TE-RMS, including significant cytoskeletal rearrangement and nuclear elongation. The unique cytoskeletal and nuclear architecture of TE-RMS astrocytes mimics astrocytes in the endogenous rat RMS. Advanced imaging techniques reveal the unique morphology of TE-RMS cells that has yet to be described of astrocytes in vitro. The TE-RMS offers a novel platform to elucidate astrocyte cytoskeletal and nuclear dynamics and their relationship to cell behavior and function.