Neuroscience
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More than thirty years of medical treatment with the use of vagal nerve stimulation (VNS) has shown that this therapeutic procedure works in a number of homeostatic disturbances. Although the clinical usage of VNS has a long history, our knowledge about the central mechanisms underlying this treatment is still limited. In the present paper we review the effects of VNS on brain oscillations as a possible electrophysiological bio-marker of VNS efficacy. ⋯ We consciously did not focus on epileptiform activity understood as a pathologic oscillatory activity, which was widely discussed in the numerous previously published reviews. The main conclusion of the present paper is that further, well-designed experiments on laboratory animals are absolutely necessary to address the electrophysiological issues. These will fill a number of gaps in our present knowledge of the central mechanisms underlying VNS therapy.
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Embodied cognition research indicates that sensorimotor training can influence action concept processing. Yet, most studies employ isolated (pseudo)randomized stimuli and require repetitive single-effector responses, thus lacking ecological validity. Moreover, the neural signatures of these effects remain poorly understood. ⋯ Conversely, static videogame playing yielded no specific effect on any linguistic category and did not modulate functional connectivity. Together, these findings suggest that action-verb processing and key neural correlates can be focally influenced by full-body motor training in a highly ecological setting. Our study illuminates the role of situated experience and sensorimotor circuits in action-concept processing, addressing calls for naturalistic insights on language embodiment.
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Developmental sevoflurane exposure leads to widespread neuronal cell death known as sevoflurane-induced neurotoxicity (SIN). Receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL)-driven necroptosis plays an important role in cell fate. Previous research has shown that inhibition of RIPK1 activity alone did not attenuate SIN. ⋯ Finally, the administration of the RIPK3 inhibitor GSK'872 relieved sevoflurane-induced spatial and emotional disorders without influence on locomotor activity. Altogether, these results illustrate that ZBP1 senses cytosolic mtDNA to induce RIPK3/MLKL-driven necroptosis in SIN. Elucidating the role of necroptosis in SIN will provide new insights into understanding the mechanism of anesthetic exposure in the developing brain.
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Cellular senescence is an important contributor to aging and age-related diseases such as Alzheimer's disease (AD). Senescent cells are characterized by a durable cell proliferation arrest and the acquisition of a proinflammatory senescence-associated secretory phenotype (SASP), which participates in the progression of neurodegenerative disorders. Clearance of senescent glial cells in an AD mouse model prevented cognitive decline suggesting pharmacological agents targeting cellular senescence might provide novel therapeutic approaches for AD. Δ133p53α, a natural protein isoform of p53, was previously shown to be a negative regulator of cellular senescence in primary human astrocytes, with clinical implications from its diminished expression in brain tissues from AD patients. ⋯ Our data suggest that Aβ-induced astrocyte cellular senescence is associated with accelerated DNA damage, and upregulation of full-length p53 and its senescence-inducing target gene p21WAF1. We also show that exogenously enhanced expression of Δ133p53α rescues human astrocytes from Aβ-induced cellular senescence and SASP through both protection from DNA damage and dominant-negative inhibition of full-length p53, leading to inhibition of Aβ-induced, astrocyte-mediated neurotoxicity. The results presented here demonstrate that Δ133p53α manipulation could modulate cellular senescence in the context of AD, possibly opening new therapeutic avenues.
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For decades, Izquierdo and colleagues contributed to building the notion that declarative memory requires different processes at the molecular and systems levels. This review aims to discuss part of Izquierdo's legacy, mainly but not exclusively that related to fear memory. ⋯ Then, the underlying processes of declarative memory are depicted, discussing the formation, the nature and the progression of the memory trace in short-term and long-term memory, and describing the involvement of some molecular cascades in the hippocampal formation, mesocortex and frontal areas. Potential contributions to therapy or understanding cognitive processes are mentioned.