The Journal of neuroscience : the official journal of the Society for Neuroscience
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Neuropathic pain is a chronic condition that occurs frequently after nerve injury and induces hypersensitivity or allodynia characterized by aberrant neuronal excitability in the spinal cord dorsal horn. Fibronectin leucine-rich transmembrane protein 3 (FLRT3) is a modulator of neurite outgrowth, axon pathfinding, and cell adhesion, which is upregulated in the dorsal horn following peripheral nerve injury. However, the function of FLRT3 in adults remains unknown. ⋯ Conversely, FLRT3 inhibition with antibodies attenuated mechanically induced pain after nerve damage. These findings suggest that FLRT3 is produced by injured DRG neurons and increases neuronal excitability in the dorsal horn, leading to pain sensitization. Neuropathic pain induction is a novel function of FLRT3.
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There is an urgent need to understand the relationships between amyloid-β (Aβ) and tau in the progression of Alzheimer's disease to identify treatment targets. Here we examine reciprocal predictions of brain Aβ burden quantified by positron emission tomography and CSF concentrations of Aβ42 and phosphorylated tau (p-tau). Each biomarker was examined over 48 months in two separate cross-lagged models; one in asymptomatic healthy elderly people (men and women), and one in patients with Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI). ⋯ Phosphorylated tau concentrations specifically predicted amyloid deposition. In Alzheimer's disease patients, although amyloid deposition and CSF amyloid changes continued to "cascade", there was no evidence to suggest that amyloid and tau biomarkers predicted each other, although both amyloid deposition and CSF tau progression predicted cognitive decline independently. Taking advantage of repeated amyloid PET and CSF measures, this dynamic view offers new insight into the progression of Alzheimer's disease biomarkers and their relationships with cognitive decline.
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The landscape of gender in education and the workforce has shifted over the past decades: women have made gains in representation, equitable pay, and recognition through awards, grants, and publications. Despite overall change, differences persist in the fields of science, technology, engineering, and mathematics (STEM). This Viewpoints article on gender disparities in STEM offers an overarching perspective by addressing what the issues are, why the issues may emerge, and how the issues may be solved. ⋯ Given its prevalence and persistence, implicit bias warrants a central focus for research and application. Finally, in Part 3, the current knowledge is presented on interventions to change individuals' beliefs and behaviors, as well as organizational culture and practices. The moral issues surrounding equal access aside, understanding and addressing the complex issues surrounding gender in STEM are important because of the possible benefits to STEM and society that will be realized only when full participation of all capable and qualified individuals is guaranteed.
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Multicenter Study
Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP.
Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various CNS diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Here, we investigated the important functions of circRNA TLK1 (circTLK1) in this process. ⋯ The levels of circTLK1 were significantly increased in the brain tissue and plasma isolated from animal models of ischemic stroke and patients. Knockdown of circTLK1 significantly decreased infarct volumes, attenuated neuronal injury, and improved subsequent long-term neurological deficits. To our knowledge, these results provide the first definitive evidence that circTLK1 is detrimental in ischemic stroke.
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Opioid-induced hyperalgesia (OIH) is a serious adverse event produced by opioid analgesics. Lack of an in vitro model has hindered study of its underlying mechanisms. Recent evidence has implicated a role of nociceptors in OIH. ⋯ We report on an in vitro model of nociceptor neuroplasticity mediating this opioid-induced hyperalgesia (OIH) and priming induced by fentanyl. Using this model, we have found qualitative and quantitative differences between cultured nociceptors from opioid-naive and opioid-primed animals, and provide evidence for the important role of nociceptor μ-opioid receptor-mediated calcium signaling and peripheral protein translation in the weakly IB4-binding population of nociceptors in OIH. These findings provide information useful for the design of therapeutic strategies to alleviate OIH, a serious adverse event of opioid analgesics.