Neuroscientist最新文献

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that is associated with long-lasting memories of traumatic experiences. Extinction and discrimination of fear memory have become therapeutic targets for PTSD. Newly developed optogenetics and advanced in vivo imaging techniques have provided unprecedented spatiotemporal tools to characterize the activity, connectivity, and functionality of specific cell types in complicated neuronal circuits. The use of such tools has offered mechanistic insights into the exquisite organization of the circuitry underlying the extinction and discrimination of fear memory. This review focuses on the acquisition of more detailed, comprehensive, and integrated neural circuits to understand how the brain regulates the extinction and discrimination of fear memory. A future challenge is to translate these researches into effective therapeutic treatment for PTSD from the perspective of precise regulation of the neural circuits associated with the extinction and discrimination of fear memories.

The use of tools to perturb brain activity can generate important insights into brain physiology and offer valuable therapeutic approaches for brain disorders. Furthermore, the potential of such tools to enhance normal behavior has become increasingly recognized, and this has led to the development of various noninvasive technologies that provides a broader access to the human brain. While providing a brief survey of brain manipulation procedures used in the past decades, this review aims at stimulating an informed discussion on the use of these new technologies to investigate the human. It highlights the importance to revisit the past use of this unique armamentarium and proceed to a detailed analysis of its present state, especially in regard to human behavioral regulation.

As resident immune cells of the brain, microglia serve pivotal roles in regulating neuronal function under both physiological and pathological conditions, including aging and the most prevalent neurodegenerative disease, Alzheimer's disease (AD). Instructed by neurons, microglia regulate synaptic function and guard brain homeostasis throughout life. Dysregulation of microglial function, however, can lead to dire consequences, including aggravated cognitive decline during aging and exacerbated neuropathology in diseases. The triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial function. Loss-of-function variants of TREM2 are associated with an increased risk of AD. TREM2 orchestrates the switch of microglial transcriptome programming that modulates microglial chemotaxis, phagocytosis, and inflammatory responses, as well as microglial regulation of synaptic function in health and disease. Intriguingly, the outcome of microglial/TREM2 function is influenced by age and the context of neuropathology. This review summarizes the rapidly growing research on TREM2 under physiological conditions and in AD, particularly highlighting the impact of TREM2 on neuronal function.

Biobanking has emerged as a strategic challenge to promote knowledge on neurological diseases, by the application of translational research. Due to the inaccessibility of the central nervous system, the advent of biobanks, as structure collecting biospecimens and associated data, are essential to turn experimental results into clinical practice. Findings from basic research, omics sciences, and in silico studies, definitely require validation in clinically well-defined cohorts of patients, even more valuable when longitudinal, or including preclinical and asymptomatic individuals. Finally, collecting biological samples requires a great effort to guarantee respect for transparency and protection of sensitive data of patients and donors. Since the European General Data Protection Regulation 2016/679 has been approved, concerns about the use of data in biomedical research have emerged. In this narrative review, we focus on the essential role of biobanking for translational research on neurodegenerative diseases. Moreover, we address considerations for biological samples and data collection, the importance of standardization in the preanalytical phase, data protection (ethical and legal) and the role of donors in improving research in this field.

Alzheimer's disease (AD) is a debilitating age-related neurodegenerative condition. Unbiased genetic studies have implicated a central role for microglia, the resident innate immune cells of the central nervous system, in AD pathogenesis. On-going efforts are clarifying the biology underlying these associations and the microglial pathways that are dysfunctional in AD. Several genetic risk factors converge to decrease the function of activating microglial receptors and increase the function of inhibitory receptors, resulting in a seemingly dampened microglial phenotype in AD. Moreover, many of these microglial proteins that are genetically associated with AD appear to interact and share pathways or regulatory mechanisms, presenting several points of convergence that may be strategic targets for therapeutic intervention. Here, we review some of these studies and their implications for microglial participation in AD pathogenesis.

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.