Altered Spinal Homeostasis and Maladaptive Plasticity in GFAP Null Mice Following Peripheral Nerve Injury.

The maladaptive response of the central nervous system (CNS) following nerve injury is primarily linked to the activation of glial cells (reactive gliosis) that produce an inflammatory reaction and a wide cellular morpho-structural and functional/metabolic remodeling. Glial acidic fibrillary protein (GFAP), a major protein constituent of astrocyte intermediate filaments (IFs), is the hallmark of the reactive astrocytes, has pleiotropic functions and is significantly upregulated in the spinal cord after nerve injury. Here, we investigated the specific role of GFAP in glial reaction and maladaptive spinal cord plasticity following sciatic nerve spared nerve injury (SNI) in GFAP KO and wild-type (WT) animals. We evaluated the neuropathic behavior (thermal hyperalgesia, allodynia) and the expression of glial (vimentin, Iba1) and glutamate/GABA system markers (GLAST, GLT1, EAAC1, vGLUT, vGAT, GAD) in lumbar spinal cord sections of KO/WT animals. SNI induced neuropathic behavior in both GFAP KO and WT mice, paralleled by intense microglial reaction (Iba1 expression more pronounced in KO mice), reactive astrocytosis (vimentin increase) and expression remodeling of glial/neuronal glutamate/GABA transporters. In conclusion, it is conceivable that the lack of GFAP could be detrimental to the CNS as it lacks a critical sensor for neuroinflammation and morpho-functional-metabolic rewiring after nerve injury. Understanding the maladaptive morpho-functional changes of glial cells could represent the first step for a new glial-based targeted approach for mechanisms of disease in the CNS.

Cross Talk at the Cytoskeleton-Plasma Membrane Interface: Impact on Neuronal Morphology and Functions.

The cytoskeleton and its associated proteins present at the plasma membrane not only determine the cell shape but also modulate important aspects of cell physiology such as intracellular transport including secretory and endocytic pathways. Continuous remodeling of the cell structure and intense communication with extracellular environment heavily depend on interactions between cytoskeletal elements and plasma membrane. This review focuses on the plasma membrane-cytoskeleton interface in neurons, with a special emphasis on the axon and nerve endings. We discuss the interaction between the cytoskeleton and membrane mainly in two emerging topics of neurobiology: (i) production and release of extracellular vesicles and (ii) local synthesis of new proteins at the synapses upon signaling cues. Both of these events contribute to synaptic plasticity. Our review provides new insights into the physiological and pathological significance of the cytoskeleton-membrane interface in the nervous system.