Brain-X最新文献

The safeguarding of animal welfare holds a deep-rooted history within public institutions and legislative structures, with the objective of enhancing the comfort and overall wellbeing of animals throughout the entire experimental process. It is paramount to harmonize the enhancement of animal welfare with medical research practices, as this is pivotal in mitigating factors that impede modeling precision and prioritizing their welfare. This commitment has nurtured innovation in advanced experimental methodologies and welfare evaluation techniques. The classic 3Rs principle-replacement, reduction, and refinement-serves as a fundamental cornerstone for advancing the welfare of model animals. The establishment of appropriate metrics for animal welfare, rooted in the 3Rs principle, will propel progress in related fields. This review delves into the evolution of animal ethics and the 3R principles, alongside strategies to elevate the welfare of various model animals utilized in neuroscience, encompassing non-human primates, rodents, zebrafish, and other species. The aim of this review is to clarify the notion of welfare in this context and to evaluate the merits and constraints of utilizing model animals in neuroscience research. This, in essence, may contribute to bolstering animal protection and standardizing their use in research endeavors. Additionally, the pursuit of novel modeling methodologies is imperative to provide superior alternatives for neuroscience research.

Noninherited diseases and age-associated vision loss are often associated with retinal degeneration. The retina is a postmitotic neural tissue lacking endogenous regeneration capacity. Therefore, understanding the mechanism of retinal degeneration in diseases is pivotal. Posttranslational modifications (PTMs) determine protein function during physiological and pathological processes, including signal transduction, protein localization, and protein activation. Advanced detection technologies have revealed over 400 different PTMs including acetylation, methylation, phosphorylation, ubiquitination and SUMOylation. Here, we discuss PTMs in retinal degeneration diseases to aid in our understanding of their molecular basis and suggest potential future clinical treatment.

A schematic diagram of a proposed neural circuit for high temperature-induced feeding inhibition. Acute high temperature exposure activates excitatory neurons in the parabrachial nucleus brain area, promotes the release of vascular endothelial growth factor A from tanycytes, and acts on agouti-related protein neurons in the ARC brain area to inhibit feeding behavior.

The incidence of affective disorders, of which major depression disorder (MDD) and bipolar disorder (BD) are two main types, has increased rapidly in recent years. They significantly impact patients, their families, and society. However, while affective disorders have become a major issue worldwide, their pathogenesis remains unclear. In the last 6 years, research using magnetic resonance imaging (MRI) and genetic data has gained prominence in understanding their pathophysiology and etiology. This systematic review collected the studies of MDD and BD research published between January 1, 2018, and February 1, 2024, focusing on studies using MRI and genetic data and indexed in the Web of Science and PubMed database. It aims to investigate the similarities and differences in their imaging phenotypes and underlying molecular bases. After exclusions, a total of 80 articles were included in this review. Research on MDD and BD reveals the critical role of epigenetic modifications, such as DNA methylation, in brain structure and function changes. The genes and pathways implicated in MDD are directly associated with depressive symptoms. In contrast, those implicated in BD are associated with mood regulation and cognitive functions. In addition, functional imaging studies have revealed that abnormalities in MDD are frequently concentrated in regions involved in emotion regulation and stress response. In contrast, those in BD are frequently concentrated in the neural circuits related to reward processing and emotional stability. Further multimodal and multiscale studies are needed to advance the field of mood disorder research.

As living standards improve, mental and physical health have been gaining increasing attention. Presently, depression is one of the most severe mental health issues. Depression affects the quality of life of affected individuals because it lasts for a very long time and is generally difficult to cure. Currently, pharmacotherapy and psychotherapy are the two main approaches for treating depression. However, some principles and characteristics of pharmacotherapy remain unclear, and its side effects are significant and noticeable. In addition, ordinary psychotherapy requires the assistance of a qualified psychotherapist, which is usually hard to find and expensive. Both methods are burdensome to the patients, making it difficult for them to benefit. As an easy-to-obtain therapy, music therapy has been recommended by physicians as an auxiliary therapy for various diseases to regulate patients' emotions and help the primary treatment methods to obtain better therapeutic effects. This review investigates and summarizes recent articles on the pathogenesis of depression and the effects of music therapy on depression. Its results show that music therapy is effective and available. However, a systematic treatment plan has not yet been formulated due to the lack of samples and short follow-up times. Future studies should include more samples and follow-up patients after the treatment period to address the continuous effect and principle of music therapy.

In a groundbreaking study, Rezai et al. unveiled a promising avenue for treating Alzheimer's disease (AD) using aducanumab and a cutting-edge delivery method¹ (Figure 1A). The team employed magnetic resonance-guided focused ultrasound (MRgFUS) to transiently open the blood–brain barrier (BBB), facilitating the transport of the drug from the blood circulation to the brain tissue. This resulted in a remarkable reduction in amyloid deposition in the treated cerebral area in three human patients. The study counters the drug delivery barriers of the brain by demonstrating the potential efficacy of this innovative approach in treating Alzheimer's.

MRgFUS stands out as a pivotal modality in brain drug delivery; it offers distinctive advantages, particularly in achieving high spatiotemporal resolution. This technology selectively and reversibly opens the BBB, primarily through the paracellular pathway. This noninvasive methodology presents a compelling approach to increasing the brain parenchyma's permeability to drugs. One key feature lies in the capacity to engineer the volume, shape, and depth of the focal spot in the brain tissue. This engineered precision caters to the specific requirements of treating diverse neurological diseases. The adaptability and precision of MRgFUS open avenues for targeted and efficacious interventions in the intricate landscape of brain-related pathologies.

Beyond the anticipated benefits of enhanced aducanumab (an FDA-approved amyloid beta-directed human monoclonal antibody indicated to treat Alzheimer's disease) delivery to the brain, the study implicated the intricate dynamics of drug/toxic complex diffusion and clearance within the human brain parenchyma. Notably, although the scientific discussion around the benefits of aducanumab is ongoing, ultrasound waves not only facilitate BBB opening but also interact with the brain parenchyma beyond the BBB to induce multiple effects^{2, 3} that could account for the overall benefit (Figure 1B).

Considering the importance of the extracellular space (ECS), perivascular space (PVS), and cerebrospinal fluid flow dynamics in modulating drug diffusion, distribution, and waste clearance,⁴ several questions remain that require further investigation. First, does ultrasound expand the ECS? Second, does it impact the PVS? Third, can ultrasound enhance flow transport, improving the clearance of antibodies and degraded amyloid fragments? Fourth, how does ultrasound interact with brain cells (e.g., neurons, astrocytes, etc.)? Fifth, does any mechanical activation of the signaling pathway have an impact? Finally, how can the technology be translated and extended to increase the efficacy of other treatment modalities enabled by larger particles, such as antibody–drug conjugates, adeno-associated viruses, and lipid nanoparticles?

Some of these aspects have been studied in the preclinical animals' m

Synthetic biomaterials are emerging candidate solutions for treating large bone defects. However, the clinical performances of most synthetic materials are not satisfactory, with the need for improvement in design and synthesis. Although bone is highly innervated, the central role during healing of the peripheral nervous system, and in particular sensory nerves (SNs), has only recently been acknowledged. SNs can improve osteogenic differentiation of bone marrow stem/stromal cells through neurotransmitters and peptides; the interplay between SNs and the vascular system also facilitates vascular network reconstruction, indirectly facilitating bone healing. These factors suggest the importance of SNs in bone healing, a vital point that has been overlooked in bone biomaterial design until very recently. SN regeneration represents a novel direction in the development of biomaterials for bone regeneration. The current perspective paper summarizes the cellular and molecular mechanisms under the regulatory influence of SNs in the bone healing process and outlines the recent advances in biomaterials for innervated bone tissue regeneration. This establishes potential future directions for bone engineering biomaterial design.

Alzheimer's disease (AD) is a type of dementia characterized by a decline in brain function, which leads to the inability to perform activities independently. Many researchers recognize abnormalities related to beta-amyloid as the main cause of the disease (i.e., the beta-amyloid hypothesis), but aging, genetics, coronary heart disease, environmental factors, gender, and other risk factors may also contribute to AD development. Three drugs with different mechanisms are available for AD treatment: cholinesterase inhibitors, N-methyl d-aspartate, and aducanumab. This study reviewed the therapies that are already applied in clinical practice and those that are currently being investigated for clinical use. These therapies include not only pharmacological treatments but also non-pharmacological treatments, such as gut flora therapy and music therapy. A comprehensive understanding of these therapies is necessary to enable early intervention, improve patients' physical and mental conditions, delay the occurrence and development of AD, and extend patients' healthy lifespans.