Neuroscience
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Inflammation contributes to amyloid beta (Aβ) aggregation and neuron loss in Alzheimer's disease (AD). Meanwhile, tumor necrosis factor-α (TNF-α) inhibitors present strong effect on suppressing inflammation. Thus, this study aimed to investigated the effect and molecular mechanism of etanercept (ETN) (a commonly used TNF-α inhibitor) on neuron injury and neuroinflammation in AD. ⋯ Besides, ETN treatment reduced neuron injury (reflected by Hematoxylin-Eosin (HE) and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assays) and levels of pro-inflammatory cytokines (including TNF-α, interleukin-1β, Interleukin-6 and CCL2) in AD mice. Moreover, ETN repressed the activation of c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) pathways in AD both in vitro and in vivo. In conclusion, ETN exerts neuroprotective function via inactivating JNK and NF-κB pathways in AD, indicating the potential of ETN for improving AD management.
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Large cholinergic neurons (V0c neurons; aka, partition cells) in the spinal cord project profusely to motoneurons on which they form C-terminal contacts distinguished by their specialized postsynaptic subsurface cisterns (SSCs). The V0c neurons are known to be rhythmically active during locomotion and release of acetylcholine (ACh) from their terminals is known to modulate the excitability of motoneurons in what appears to be a task-dependent manner. Here, we present evidence that a subpopulation of V0c neurons express the gap junction forming protein connexin36 (Cx36), indicating that they are coupled by electrical synapses. ⋯ We present evidence that fast vs. slow motoneurons have a greater abundance of these terminals and fast motoneurons also have the highest density that were eGFP+. Thus, our results indicate that a subpopulation of V0c neurons projects preferentially to fast motoneurons, suggesting that the capacity for synchronous activity conferred by electrical synapses among networks of coupled V0c neurons enhances their dynamic capabilities for synchronous regulation of motoneuron excitability during high muscle force generation. The eGFP+ vs. eGFP- V0c neurons were more richly innervated by serotonergic terminals, suggesting their greater propensity for regulation by descending serotonergic systems.