Neuronal Function Research Articles

From immune response to mental health: neutrophils in schizophrenia

Schizophrenia is a multifaceted psychiatric disorder with a complex etiology that includes genetic, environmental, and immunological factors. Emerging research has increasingly focused on the role of the immune system, particularly neutrophils, in the pathogenesis of schizophrenia. Neutrophils, the most abundant type of white blood cells, are crucial in the body’s defense mechanisms against infections and in the regulation of inflammation. This review explores the evolving evidence that implicates neutrophils in schizophrenia, highlighting their potential contribution to the disorder’s onset and progression through mechanisms such as neuroinflammation and oxidative stress. Recent studies have demonstrated elevated neutrophil counts and neutrophil-to-lymphocyte ratios (NLR) in individuals with schizophrenia, correlating with the severity of psychotic symptoms and cognitive impairments. Furthermore, genetic and molecular analyses have revealed abnormalities in neutrophil function and immune-related gene expression in schizophrenia patients. These findings suggest that neutrophil dysfunction and the resulting chronic inflammation could play a significant role in the disorder’s pathophysiology, affecting neuronal function and contributing to the clinical manifestations of schizophrenia. Neutrophil-related biomarkers, such as NLR, could aid in the diagnosis and monitoring of disease progression. Additionally, targeting neutrophil activity and associated inflammatory pathways presents a promising avenue for developing new therapeutic interventions. This review underscores the need for further research to elucidate the precise mechanisms by which neutrophils influence schizophrenia and to explore potential treatments that could improve outcomes for patients.

Exploring non-canonical targets in Alzheimer’s disease: a departure from the norm

AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, and cognitive decline. Despite advances in understanding AD pathophysiology and the expansion of therapeutic options over the past three decades, the disease remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring the need for innovative treatment approaches beyond symptomatic relief. This calls for a re-examination of AD pathology to identify potential therapeutic targets that go beyond conventional strategies. This review highlights four of the most promising non-canonical therapeutic targets: oligodendrocytes, the blood–brain barrier (BBB), neuroimmunometabolism, and the coagulation system. These components are crucial for maintaining the integrity and proper function of neurons and the brain, playing key roles in the progression of AD. Oligodendrocytes, for example, are essential for myelination and neuronal support, while BBB dysfunction can lead to impaired clearance of toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses in the brain and dysregulation of the coagulation system has been linked to increased neuroinflammation and vascular abnormalities in AD. Recent discoveries in these fields provide new avenues for understanding the disease and identifying potential therapeutic targets. By exploring these non-canonical pathways, future research may offer breakthroughs in treating AD, moving beyond symptomatic management towards disease-modifying strategies.

Sex Differences in the Neuroendocrine Stress Response: A View from a CRH-Reporting Mouse Line

Corticotropin-releasing hormone (CRH) neurons within the paraventricular hypothalamic nucleus (PVH) play a crucial role in initiating the neuroendocrine response to stress and are also pivotal in coordination of autonomic, metabolic, and behavioral stress reactions. Although the role of parvocellular CRHPVH neurons in activation of the hypothalamic–pituitary–adrenal (HPA) axis is well established, the distribution and function of CRH-expressing neurons across the whole central nervous system are less understood. Stress responses activate complex neural networks, which differ depending on the type of stressor and on the sex of the individual. Because of the technical difficulties of localizing CRH neurons throughout the rodent brain, several CRH reporter mouse lines have recently been developed. In this study, we used Crh-IRES-Cre;Ai9 reporter mice to examine whether CRH neurons are recruited in a stressor- or sex-specific manner, both within and outside the hypothalamus. In contrast to the clear sexual dimorphism of CRH-mRNA-expressing neurons, quantification of CRH-reporting, tdTomato-positive neurons in different stress-related brain areas revealed only subtle differences between male and female subjects. These results strongly imply that sex differences in CRH mRNA expression occur later in development under the influence of sex steroids and reflects the limitations of using genetic reporter constructs to reveal the current physiological/transcriptional status of a specific neuron population. Next, we compared the recruitment of stress-related, tdTomato-expressing (putative CRH) neurons in male and female Crh-IRES-Cre;Ai9 reporter mice that had been exposed to predator odor. In male mice, fox odor triggered more c-Fos in the CRH neurons of the paraventricular hypothalamic nucleus, central amygdala, and anterolateral bed nucleus of the stria terminalis compared to females. These results indicate that male mice are more sensitive to predator exposure due to a combination of hormonal, environmental, and behavioral factors.

PKA regulation of neuronal function requires the dissociation of catalytic subunits from regulatory subunits

Protein kinase A (PKA) plays essential roles in diverse cellular functions. However, the spatiotemporal dynamics of endogenous PKA upon activation remain debated. The classical model predicts that PKA catalytic subunits dissociate from regulatory subunits in the presence of cAMP, whereas a second model proposes that catalytic subunits remain associated with regulatory subunits following physiological activation. Here, we report that different PKA subtypes, as defined by the regulatory subunit, exhibit distinct subcellular localization at rest in CA1 neurons of cultured hippocampal slices. Nevertheless, when all tested PKA subtypes are activated by norepinephrine, presumably via the β-adrenergic receptor, catalytic subunits translocate to dendritic spines but regulatory subunits remain unmoved. These differential spatial dynamics between the subunits indicate that at least a significant fraction of PKA dissociates. Furthermore, PKA-dependent regulation of synaptic plasticity and transmission can be supported only by wildtype, dissociable PKA, but not by inseparable PKA. These results indicate that endogenous PKA regulatory and catalytic subunits dissociate to achieve PKA function in neurons.

Deep functional measurements of Fragile X syndrome human neurons reveal multiparametric electrophysiological disease phenotype

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by hypermethylation of expanded CGG repeats (>200) in the FMR1 gene leading to gene silencing and loss of Fragile X Messenger Ribonucleoprotein (FMRP) expression. FMRP plays important roles in neuronal function, and loss of FMRP in mouse and human FXS cell models leads to aberrant synaptic signaling and hyperexcitability. Multiple drug candidates have advanced into clinical trials for FXS, but no efficacious treatment has been identified to date, possibly as a consequence of poor translation from pre-clinical animal models to human. Here, we use a high resolution all-optical electrophysiology platform applied to multiple FXS patient-derived and CRISPR/Cas9-generated isogenic neuronal cell lines to develop a multi-parametric FXS disease phenotype. This neurophysiological phenotype was optimized and validated into a high throughput assay based on the amount of FMRP re-expression and the number of healthy neurons in a mosaic network necessary for functional rescue. The resulting highly sensitive and multiparameter functional assay can now be applied as a discovery platform to explore new therapeutic approaches for the treatment of FXS.

Dexmedetomidine alleviates intestinal ischemia/reperfusion injury by modulating intestinal neuron autophagy and mitochondrial homeostasis via Nupr1 regulation

Intestinal ischemia/reperfusion injury (I/R) is a common yet challenging-to-treat condition, presenting a significant clinical challenge. This study aims to investigate the protective mechanisms of Dexmedetomidine (Dex) against I/R injury, with a particular focus on its role in regulating autophagy activity in intestinal neurons and maintaining mitochondrial homeostasis. Experimental findings demonstrate that Dex can mitigate intestinal damage induced by I/R through the modulation of autophagy activity and mitochondrial function in intestinal neurons by suppressing the expression of Nupr1. This discovery sheds light on a new molecular mechanism underlying the potential efficacy of Dex in treating intestinal I/R injury, offering valuable insights for clinical therapy.

Nucleic acid sensing in the central nervous system: Implications for neural circuit development, function, and degeneration.

Nucleic acids are a critical trigger for the innate immune response to infection, wherein pathogen-derived RNA and DNA are sensed by nucleic acid sensing receptors. This subsequently drives the production of type I interferon and other inflammatory cytokines to combat infection. While the system is designed such that these receptors should specifically recognize pathogen-derived nucleic acids, it is now clear that self-derived RNA and DNA can also stimulate these receptors to cause aberrant inflammation and autoimmune disease. Intriguingly, similar pathways are now emerging in the central nervous system in neurons and glial cells. As in the periphery, these signaling pathways are active in neurons and glia to present the spread of pathogens in the CNS. They further appear to be active even under steady conditions to regulate neuronal development and function, and they can become activated aberrantly during disease to propagate neuroinflammation and neurodegeneration. Here, we review the emerging new roles for nucleic acid sensing mechanisms in the CNS and raise open questions that we are poised to explore in the future.

New evidence of vascular defects in neurodegenerative diseases revealed by single cell RNA sequencing.

Neurodegenerative diseases (NDs) involve the progressive loss of neuronal structure or function in the brain and spinal cord. Despite their diverse etiologies, NDs manifest similar pathologies. Emerging research identifies vascular defects as a previously neglected hallmark of NDs. The development and popularization of single-cell RNA sequencing (scRNA-seq) technologies have significantly advanced our understanding of brain vascular cell types and their molecular characteristics, including gene expression changes at the single-cell level in NDs. These unprecedented insights deepen our understanding of the pathogenic mechanisms underlying NDs. However, the occurrence and role of vascular defects in disease progression remain largely unexplored. In this paper, we systematically summarize recent advances in the structure and organization of the central nervous system vasculature in mice, healthy individuals, and patients with NDs, focussing primarily on disease-specific alterations in vascular cell types or subtypes. Combining scRNA-seq with pathology evidence, we propose that vascular defects, characterized by disruptions in cell types and structural integrity, may serve as common early features of NDs. Finally, we discuss several pathways through which vascular defects in NDs lead to neuronal degeneration. A deeper understanding of the causes and contributions of vascular defects to NDs aids in elucidating the pathogenic mechanisms and developing meaningful therapeutic interventions.

Gather your neurons and model together: Community times ahead.

Bottom-up, data-driven, large-scale models provide a mechanistic understanding of neuronal functions. A new study in PLOS Biology builds a biologically realistic model of the rodent CA1 region that aims to become an accessible tool for the whole hippocampal community.

The Val66Met variant of brain-derived neurotrophic factor is linked to reduced telomere length in a military population: a pilot study

In military populations, gene-environment interactions can influence performance and health outcomes. Brain-derived neurotrophic factor (BDNF) is a central nervous system protein that is important for neuronal function and synaptic plasticity. A BDNF single nucleotide polymorphism, rs6265, leads to an amino acid substitution of valine (Val) with methionine (Met) at codon 66 (Val66Met), which may influence an individual’s response to occupational stress, and predispose military members to psychological disorders. Telomere length (TL), a novel measure of biological aging, can be used as a biomarker of stress. Accordingly, telomere shortening may be a surrogate indicator of physiological weathering due to chronic disease and stressful life events. To increase our understanding about the potential effect of the Val66Met mutation on the human stress response, we evaluated the relationships between Val66Met, TL, and mental health symptoms in a military population. In this pilot study (N = 164), we observed an association between Val66Met and reduced TL (p = 0.048). There was no relationship between Val66Met and mental health symptoms. These results support the investigation of gene-environment interactions, and their potential influence on TL due to occupational stress such as military service.

Primary cortical cell tri-culture to study effects of amyloid-β on microglia function and neuroinflammatory response.

Microglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of critical cell types in the same culture. We employed a rat primary tri-culture (neurons, astrocytes, and microglia) model and compared it to co-culture (neurons and astrocytes) and mono-culture (microglia) to study microglial function (i.e., motility and Aβ clearance) and proteomic response to exogenous Aβ. The cultures were exposed to fluorescently-labeled Aβ (FITC-Aβ) particles for varying durations. Epifluorescence microscopy images were analyzed to quantify the number of FITC-Aβ particles and assess cytomorphological features. Cytokine profiles from conditioned media were obtained. Live-cell imaging was employed to extract microglia motility parameters. FITC-Aβ particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aβ particles, as confirmed via epifluorescence and confocal microscopy. FITC-Aβ treatment significantly increased microglia size, but had no significant effect on neuronal surface coverage or astrocyte size. Upon FITC-Aβ treatment, there was a significant increase in proinflammatory cytokines in tri-culture, but not in co-culture. Aβ treatment altered microglia motility evident as a swarming-like motion. The results suggest that neuron-astrocyte-microglia interactions influence microglia function and highlight the utility of the tri-culture model for studies of neuroinflammation, neurodegeneration, and cell-cell communication.

Autophagy in the nervous system: general principles and specific functions

Autophagy is an intracellular mechanism for the isolation, transport and degradation of macromolecules and organelles. The physiological significance of autophagy lies, firstly, in maintaining the constancy of the intracellular environment through the timely disposal of proteins with a disrupted structure and damaged organelles. Secondly, due to the selective degradation of macromolecules, autophagy supplies the cell with monomers, which are then used by it to synthesize new compounds, which serves to ensure the rearrangement of cellular metabolism in the processes of cell differentiation, ontogenesis and adaptation to environmental challenges. Autophagy is an extremely important mechanism for maintaining normal functioning of postmitotic and differentiated cells, including neurons. Impaired neuronal autophagy leads to the formation of aggregated protein plaques, the accumulation of damaged cellular organelles, defects in the structure of processes and neuronal degeneration, which often accompanies to the progression of some forms of neurodegenerative diseases. In addition, the role of autophagy in synaptic plasticity and memory mechanisms has been established. Since autophagy has a significant impact on cellular metabolism, the study of the regulation and main pathways of this mechanism may be crucial in the elaboration of means and approaches to the treatment and prevention of many pathologies that progress with age. This review describes the basic concepts of the autophagy process, summarizes the key functions of autophagy in cells, and also presents current data on its role in ensuring the normal metabolism and implementation of specific functions of neurons.

Hormonal actions in the medial preoptic area governing parental behaviour: Novel insights from new tools.

The importance of hormones in mediating a behavioural transition in mammals from a virgin or non-parenting state to parental state was established around 50 years ago. Extensive research has since revealed a highly conserved neural circuit that underlies parental behaviour both between sexes and between mammalian species. Within this circuit, hormonal action in the medial preoptic area of the hypothalamus (MPOA) has been shown to be key in timing the onset of parental behaviour with the birth of offspring. However, the mechanism underlying how hormones act in the MPOA to facilitate this change in behaviour has been unclear. Technical advances in neuroscience, including single cell sequencing, novel transgenic approaches, calcium imaging, and optogenetics, have recently been harnessed to reveal new insights into maternal behaviour. This review aims to highlight how the use of these tools has shaped our understanding about which aspects of maternal behaviour are regulated by specific hormone activity within the MPOA, how hormone-sensitive MPOA neurons integrate within the wider neural circuit that governs maternal behaviour, and how maternal hormones drive changes in MPOA neuronal function during different reproductive states. Finally, we review our current understanding of hormonal modulation of MPOA-mediated paternal behaviour in males.

Discovering a novel dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitor and its impact on tau phosphorylation and amyloid-β formation

Dual-specificity tyrosine-regulated kinase 1 A (DYRK1A) is crucial in neurogenesis, synaptogenesis, and neuronal functions. Its dysregulation is linked to neurodegenerative disorders like Down syndrome and Alzheimer’s disease. Although the development of DYRK1A inhibitors has significantly advanced in recent years, the selectivity of these drugs remains a critical challenge, potentially impeding further progress. In this study, we utilised structure-based virtual screening (SBVS) from NCI library to discover novel DYRK1A inhibitors. The top-ranked compounds were then validated through enzymatic assays to assess their efficacy towards DYRK1A. Among them, NSC361563 emerged as a potent and selective DYRK1A inhibitor. It was shown to decrease tau phosphorylation at multiple sites, thereby enhancing tubulin stability. Moreover, NSC361563 diminished the formation of amyloid β and offered neuroprotective benefits against amyloid β-induced toxicity. Our research highlights the critical role of selective DYRK1A inhibitors in treating neurodegenerative diseases and presents a promising starting point for the development of targeted therapies.

Extracellular vesicles from microglial cells activated by abnormal heparan sulfate oligosaccharides from Sanfilippo patients impair neuronal dendritic arborization

BackgroundIn mucopolysaccharidosis type III (MPS III, also known as Sanfilippo syndrome), a pediatric neurodegenerative disorder, accumulation of abnormal glycosaminoglycans (GAGs) induces severe neuroinflammation by triggering the microglial pro-inflammatory cytokines production via a TLR4-dependent pathway. But the extent of the microglia contribution to the MPS III neuropathology remains unclear. Extracellular vesicles (EVs) mediate intercellular communication and are known to participate in the pathogenesis of adult neurodegenerative diseases. However, characterization of the molecular profiles of EVs released by MPS III microglia and their effects on neuronal functions have not been described.MethodsHere, we isolated EVs secreted by the microglial cells after treatment with GAGs purified from urines of Sanfilippo patients (sfGAGs-EVs) or from age-matched healthy subjects (nGAGs-EVs) to explore the EVs’ proteins and small RNA profiles using LC–MS/MS and RNA sequencing. We next performed a functional assay by immunofluorescence following nGAGs- or sfGAGs-EVs uptake by WT primary cortical neurons and analyzed their extensions metrics after staining of βIII-tubulin and MAP2 by confocal microscopy.ResultsFunctional enrichment analysis for both proteomics and RNA sequencing data from sfGAGs-EVs revealed a specific content involved in neuroinflammation and neurodevelopment pathways. Treatment of cortical neurons with sfGAGs-EVs induced a disease-associated phenotype demonstrated by a lower total neurite surface area, an impaired somatodendritic compartment, and a higher number of immature dendritic spines.ConclusionsThis study shows, for the first time, that GAGs from patients with Sanfilippo syndrome can induce microglial secretion of EVs that deliver a specific molecular message to recipient naive neurons, while promoting the neuroinflammation, and depriving neurons of neurodevelopmental factors. This work provides a framework for further studies of biomarkers to evaluate efficiency of emerging therapies.Graphical

The fate of neuronal synapse homeostasis in aging, infection, and inflammation.

Neuroplasticity is the brain's ability to reorganize and modify its neuronal connections in response to environmental stimuli, experiences, learning, and disease processes. This encompasses a variety of mechanisms, including changes in synaptic strength and connectivity, the formation of new synapses, alterations in neuronal structure and function, and the generation of new neurons. Proper functioning of synapses, which facilitate neuron-to-neuron communication, is crucial for brain activity. Neuronal synapse homeostasis, which involves regulating and maintaining synaptic strength and function in the central nervous system (CNS), is vital for this process. Disruptions in synaptic balance, due to factors like inflammation, aging, or infection, can lead to impaired brain function. This review highlights the main aspects and mechanisms underlying synaptic homeostasis, particularly in the context of aging, infection, and inflammation.

Preliminary Evidence for Neuronal Dysfunction Following Adverse Childhood Experiences: An Investigation of Salivary MicroRNA Within a High-Risk Youth Sample

Background/Objectives: Adverse childhood experiences (ACEs) are potent drivers of psychopathology and neurological disorders, especially within minoritized populations. Nonetheless, we lack a coherent understanding of the neuronal mechanisms through which ACEs impact gene expression and, thereby, the development of psychopathology. Methods: This observational pilot study used a novel marker of neuronal functioning (brain-derived micro ribonucleic acids, or miRNAs) collected via saliva to explore the connection between ACEs and neuronal gene expression in 45 adolescents with a collectively high ACE exposure (26 males and 19 females of diverse races/ethnicities, with six cumulative ACEs on average). We aimed to determine the feasibility of using salivary microRNA for probing neuronal gene expression with the goal of identifying cellular processes and genetic pathways perturbed by childhood adversity. Results: A total of 274 miRNAs exhibited reliable salivary expression (raw counts > 10 in > 10% of samples). Fourteen (5.1%) were associated with cumulative ACE exposure (p < 0.05; r’s ≥ 0.31). ACE exposure correlated negatively with miR-92b-3p, 145a-5p, 31-5p, and 3065-5p, and positively with miR-15b-5p, 30b-5p, 30c-5p, 30e-3p, 199a-3p, 223-3p, 338-3p, 338-5p, 542-3p, and 582-5p. Most relations remained significant after controlling for multiple comparisons and potential retrospective bias in ACE reporting for miRNAs with particularly strong relations (p < 0.03). We examined KEGG pathways targeted by miRNAs associated with total ACE scores. Results indicated putative miRNA targets over-represented 47 KEGG pathways (adjusted p < 0.05) involved in neuronal signaling, brain development, and neuroinflammation. Conclusions: Although preliminary and with a small sample, the findings represent a novel contribution to the understanding of how childhood adversity impacts neuronal gene expression via miRNA signaling.

Transcriptomic alterations in APP/PS1 mice astrocytes lead to early postnatal axon initial segment structural changes

Alzheimer´s disease (AD) is characterized by neuronal function loss and degeneration. The integrity of the axon initial segment (AIS) is essential to maintain neuronal function and output. AIS alterations are detected in human post-mortem AD brains and mice models, as well as, neurodevelopmental and mental disorders. However, the mechanisms leading to AIS deregulation in AD and the extrinsic glial origin are elusive. We studied early postnatal differences in AIS cellular/molecular mechanisms in wild-type or APP/PS1 mice and combined neuron-astrocyte co-cultures. We observed AIS integrity alterations, reduced ankyrinG expression and shortening, in APP/PS1 mice from P21 and loss of AIS integrity at 21 DIV in wild-type and APP/PS1 neurons in the presence of APP/PS1 astrocytes. AnkyrinG decrease is due to mRNAs and protein reduction of retinoic acid synthesis enzymes Rdh1 and Aldh1b1, as well as ADNP (Activity-dependent neuroprotective protein) in APP/PS1 astrocytes. This effect was mimicked by wild-type astrocytes expressing ADNP shRNA. In the presence of APP/PS1 astrocytes, wild-type neurons AIS is recovered by inhibition of retinoic acid degradation, and Adnp-derived NAP peptide (NAPVSIPQ) addition or P2X7 receptor inhibition, both regulated by retinoic acid levels. Moreover, P2X7 inhibitor treatment for 2 months impaired AIS disruption in APP/PS1 mice. Our findings extend current knowledge on AIS regulation, providing data to support the role of astrocytes in early postnatal AIS modulation. In conclusion, AD onset may be related to very early glial cell alterations that induce AIS and neuronal function changes, opening new therapeutic approaches to detect and avoid neuronal function loss.

RNA granules in flux: dynamics to balance physiology and pathology.

The life cycle of an mRNA is a complex process that is tightly regulated by interactions between the mRNA and RNA-binding proteins, forming molecular machines known as RNA granules. Various types of these membrane-less organelles form inside cells, including neurons, and contributecritically to various physiological processes. RNA granules are constantly in flux, change dynamically and adapt to their local environment, depending on their intracellular localization. The discovery that RNA condensates can form by liquid-liquid phase separation expanded our understanding of how compartments may be generated in the cell. Since then, a plethora of new functions have been proposed for distinct condensates in cells that await their validation in vivo. The finding that dysregulation of RNA granules (for example, stress granules) islikely toaffect neurodevelopmental and neurodegenerative diseases further boosted interest in this topic. RNA granules have various physiological functions in neurons and in the brain that we would like to focus on. We outline examples of state-of-the-art experiments including timelapse microscopy in neurons to unravel the precise functions of various types ofRNA granule. Finally, we distinguish physiologically occurring RNA condensation from aberrant aggregation, induced by artificial RNA overexpression, and present visual examples to discriminate both forms in neurons.

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related disorders, especially in Alzheimer's disease (AD) and post-traumatic stress disorder (PTSD), has been investigated extensively. In this review, we describe the unique contributions of astrocytes to synaptic plasticity and neuronal networks and discuss the role of astrocytes in different types of memory processing. In addition, we also explore the roles of astrocytes in the pathogenesis of memory-related disorders, such as AD, brain aging, PTSD and addiction, thus suggesting that targeting astrocytes may represent a potential strategy to treat memory-related neurological diseases. In conclusion, this review emphasizes that thinking from the perspective of astrocytes will provide new ideas for the diagnosis and therapy of memory-related neurological disorders.