Journal of neurophysiology
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Peripheral nerve inflammation can cause neuronal excitability changes that have been implicated in the pathogenesis of chronic pain. Although the neuroimmune interactions that lead to such physiological changes are unclear, in vitro studies suggest that the chemokine CCL2 may be involved. This in vivo study examines the effects of CCL2 on untreated and inflamed neurons and compares its effects with those of TNF-α. ⋯ In contrast, the cognate TNF-α receptor (TNFR), TNFR1, was present on untreated and inflamed neurons. In summary, CCL2 can excite inflamed C-fiber neurons with similar effects to TNF-α, although the underlying mechanisms may be different. The modulatory effects of both cytokines are limited to a subgroup of neurons, which may be subtly inflamed.
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Neonatal damage to the trigeminal nerve leads to "reactive synaptogenesis" in the brain stem sensory trigeminal nuclei. In vitro models of brain injury-induced synaptogenesis have implicated an important role for astrocytes. In this study we tested the role of astrocyte function in reactive synaptogenesis in the trigeminal principal nucleus (PrV) of neonatal rats following unilateral transection of the infraorbital (IO) branch of the trigeminal nerve. ⋯ Pharmacological blockade of astrocyte function, purinergic receptors, and thrombospondins significantly reduced or eliminated reactive synaptogenesis without changing the MII in the intact PrV. GFAP immunohistochemistry further supported these electrophysiological results. We conclude that immature astrocytes, purinergic receptors, and thrombospondins play an important role in reactive synaptogenesis in the peripherally deafferented neonatal PrV.
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Fast onset and high-level neurospecific transgene expression in vivo is of importance for many areas in neuroscience, from basic to translational, and can significantly reduce the amount of vector load required to maintain transgene expression in vivo. In this study, we tested various cis elements to optimize transgene expression at transcriptional, posttranscriptional, and posttranslational levels and combined them together to create the high-level neuronal transgene expression cassette pUNISHER. ⋯ More importantly, this cassette led to highly correlated neuronal expression in vivo and to stable transgene expression up to 30 days in the auditory brain stem with no toxicity on the characteristics of synaptic transmission and plasticity at the calyx of Held synapse. Thus the pUNISHER cassette is an ideal high-level neuronal expression cassette for use in vivo for neuroscience applications.