Frontiers in Cellular Neuroscience最新文献

Microglia are dynamic central nervous system cells crucial for maintaining homeostasis and responding to neuroinflammation, as evidenced by their varied morphologies. Existing morphology analysis often fails to detect subtle variations within the full spectrum of microglial morphologies due to their reliance on predefined categories. Here, we present MorphoGlia, an interactive, user-friendly pipeline that objectively characterizes microglial morphologies. MorphoGlia employs a machine learning ensemble to select relevant morphological features of microglia cells, perform dimensionality reduction, cluster these features, and subsequently map the clustered cells back onto the tissue, providing a spatial context for the identified microglial morphologies. We applied this pipeline to compare the responses between saline solution (SS) and scopolamine (SCOP) groups in a SCOP-induced mouse model of Alzheimer's disease, with a specific focus on the hippocampal subregions CA1 and Hilus. Next, we assessed microglial morphologies across four groups: SS-CA1, SCOP-CA1, SS-Hilus, and SCOP-Hilus. The results demonstrated that MorphoGlia effectively differentiated between SS and SCOP-treated groups, identifying distinct clusters of microglial morphologies commonly associated with pro-inflammatory states in the SCOP groups. Additionally, MorphoGlia enabled spatial mapping of these clusters, identifying the most affected hippocampal layers. This study highlights MorphoGlia's capability to provide unbiased analysis and clustering of microglial morphological states, making it a valuable tool for exploring microglial heterogeneity and its implications for central nervous system pathologies.

DNA methylation plays a crucial role in development, aging, degeneration of various tissues and dedifferentiated cells. This review explores the multifaceted impact of DNA methylation on the retina and brain during development and pathological processes. First, we investigate the role of DNA methylation in retinal development, and then focus on retinal diseases, detailing the changes in DNA methylation patterns in diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. Since the retina is considered an extension of the brain, its unique structure allows it to exhibit similar immune response mechanisms to the brain. We further extend our exploration from the retina to the brain, examining the role of DNA methylation in brain development and its associated diseases, such as Alzheimer's disease (AD) and Huntington's disease (HD) to better understand the mechanistic links between retinal and brain diseases, and explore the possibility of communication between the visual system and the central nervous system (CNS) from an epigenetic perspective. Additionally, we discuss neurodevelopmental brain diseases, including schizophrenia (SZ), autism spectrum disorder (ASD), and intellectual disability (ID), focus on how DNA methylation affects neuronal development, synaptic plasticity, and cognitive function, providing insights into the molecular mechanisms underlying neurodevelopmental disorders.

Fyn is a cytoplasmic tyrosine kinase (TK) that is a nonreceptor and a member of the Src family of kinases (SFKs). It is involved in several transduction pathways in the central nervous system (CNS), such as oligodendrocyte development, myelination, axon guidance, and synaptic transmission. Owing to its wide range of activities in the molecular signaling pathways that underpin both neuropathologic and neurodevelopmental events, Fyn has remained of great interest for more than a century. Accumulating preclinical data have highlighted the potential role of Fyn in the pathophysiology of neonatal hypoxic-ischaemic encephalopathy (HIE). By mediating important signaling pathways, Fyn may control glutamate excitotoxicity, promote neuroinflammation and facilitate the death of neurons caused by oxidative stress. In this review, we address new evidence regarding the role of Fyn in the pathogenesis of this condition, with the aim of providing a reference for the development of new strategies to improve the prognosis of neonatal HIE. In addition, we also offer insights into additional Fyn-related molecular mechanisms involved in HIE pathology.

Parkinson's disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result reproducibility and it makes it very difficult to compare the results obtained from different research groups. An alternative cellular model is the neuroblastoma BE (2)-M17 which exhibits a high basal expression of numerous dopaminergic markers such as tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). The BE (2)-M17 cells show neuronal properties, grows rapidly in conventional media, and can easily be differentiated to increase their dopaminergic phenotype. In this review, we will thoroughly explore the properties of the BE (2)-M17 cell line and discuss its potential as an excellent model for studying Parkinson's disease.

In the last years, science started to move toward a more glio-neurocentric view, in which astrocytes are hypothesized to be directly involved in cognitive functions. Indeed, astrocytes show a variety of shapes with species-specific characteristics, suggesting a specialization of roles during evolution. Interlaminar (ILA) and varicose-projection (VP-As) astrocytes show an anatomical organization that is different compared to the classical horizontal net typically formed by protoplasmic and fibrous astrocytes. ILAs show a modular architecture with the soma in the first cortical layer and processes toward the deep layers with species-specific length. VP-As reside in the deep layers of the cortex, are characterized by varicosities on the longest processes, and are individual-specific. These characteristics suggest roles that are more complex than what was theorized until now. Here, we recapitulate what we know so far from literature from the first time ILAs were described to the most recent discoveries, spanning from morphology description, hypothesis on the development to their features in diseases. For a complete glance on this topic, we included a final paragraph on which techniques and models were used to study ILAs and VP-As, and what new avenues may be opened thanks to more novel methods.

[This retracts the article DOI: 10.3389/fncel.2014.00382.].

Intracellular lysosomal trafficking and positioning are fundamental cellular processes critical for proper neuronal function. Among the diverse array of proteins involved in regulating lysosomal positioning, the Transient Receptor Potential Mucolipin 1 (TRPML1) and the Ragulator complex have emerged as central players. TRPML1, a lysosomal cation channel, has been implicated in lysosomal biogenesis, endosomal/lysosomal trafficking including in neuronal dendrites, and autophagy. LAMTOR1, a subunit of the Ragulator complex, also participates in the regulation of lysosomal trafficking. Here we report that LAMTOR1 regulates lysosomal positioning in dendrites of hippocampal neurons by interacting with TRPML1. LAMTOR1 knockdown (KD) increased lysosomal accumulation in proximal dendrites of cultured hippocampal neurons, an effect reversed by TRPML1 KD or inhibition. On the other hand, TRPML1 activation with ML-SA1 or prevention of TRPML1 interaction with LAMTOR1 using a TAT-decoy peptide induced dendritic lysosomal accumulation. LAMTOR1 KD-induced proximal dendritic lysosomal accumulation was blocked by the dynein inhibitor, ciliobrevin D, suggesting the involvement of a dynein-mediated transport. These results indicate that LAMTOR1-mediated inhibition of TRPML1 is critical for normal dendritic lysosomal distribution and that release of this inhibition or direct activation of TRPML1 results in abnormal dendritic lysosomal accumulation. The roles of LAMTOR1-TRPML1 interactions in lysosomal trafficking and positioning could have broad implications for understanding cognitive disorders associated with lysosomal pathology and calcium dysregulation.

Major depressive disorder is a complex and multifactorial condition, increasingly linked to neuroinflammation and astrocytic dysfunction. Astrocytes, along with other glial cells, beyond their classic functions in maintaining brain homeostasis, play a crucial role in regulating neuroinflammation and neuroplasticity, key processes in the pathophysiology of depression. This mini-review explores the involvement of astrocytes in depression emphasizing their mediation in neuroinflammation processes, the impact of astrocytic dysfunction on neuroplasticity, and the effect of some antidepressants on astrocyte reactivity. Recent evidence suggests that targeting astrocyte-related signaling pathways, particularly the balance between different astrocytic phenotypes, could offer promising evidence for therapeutic strategies for affective disorders. Therefore, a deeper understanding of astrocyte biology may open the way to innovative treatments aimed at mitigating depressive symptoms by impacting both neuroinflammation and imbalances in neuroplasticity.

Intracerebral hemorrhage (ICH) is a severe condition that devastatingly harms human health and poses a financial burden on families and society. Bcl-2 Associated X-protein (Bax) and B-cell lymphoma 2 (Bcl-2) are two classic apoptotic markers post-ICH. Beclin 1 offers a competitive architecture with that of Bax, both playing a vital role in autophagy. However, the interaction between Beclin 1 and Bcl-2/Bax has not been conjunctively analyzed. This review aims to examine the crosstalk between autophagy and apoptosis in ICH by focusing on the interaction and balance of Beclin 1, Bax, and Bcl-2. We also explored the therapeutic potential of Western conventional medicine and traditional Chinese medicine (TCM) in ICH via controlling the crosstalk between autophagy and apoptosis.