Alzheimer’s disease (AD) is the most frequent cause of cognitive impairment in middle-aged and older populations. There is a lack of drugs that demonstrate significant efficacy in AD, so the study of the pathogenesis of AD is of great importance. More efficacious interventions are needed, as reflected by our population’s fast aging. Synaptic plasticity is the capacity of neurons to adjust their connections, and it is strongly tied to learning and memory, cognitive function, and brain injury recovery. Changes in synaptic strength, such as long-term potentiation (LTP) or inhibition (LTD), are thought to represent the biological foundation of the early stages of learning and memory. The results of numerous studies confirm that neurotransmitters and their receptors play an important role in the regulation of synaptic plasticity. However, so far, there is no definite correlation between the function of neurotransmitters in aberrant neural oscillation and AD-related cognitive impairment. We summarized the AD process to understand the impact of neurotransmitters in the progression and pathogenesis of AD, including the current status of neurotransmitter target drugs, and the latest evidence of neurotransmitters’ function and changes in the AD process.

Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.

Background: Alzheimer's disease (AD) is a well-known neurodegenerative disease that gradually induces neural network dysfunction and progressive memory deficits. Neural network activity is represented by rhythmic oscillations that influence local field potentials (LFPs). However, changes in hippocampal neural rhythmic oscillations in the early stage of AD remain largely unexplored. Objective: This study investigated neural rhythmic oscillations in 3-month-old APP/PS1 and 5x- FAD mice to assess early neural connectivity in AD. Methods: LFPs were recorded from the hippocampal CA1 region with implanted microelectrode arrays while the mice were in the awake resting stage. Welch fast Fourier transforms, continuous wavelet transforms, and phase-amplitude coupling analyses were used to compute the power density of different frequency bands and phase-amplitude modulation indices in the LFPs. Results: Our results showed impaired theta, low gamma, and high gamma frequency band power in APP/PS1 and 5xFAD mice during the awake resting stage. AD mice also showed decreased delta, alpha, and beta frequency band power. Impaired theta-low gamma and theta-high gamma phaseamplitude coupling were observed in 5xFAD mice. Conclusion: This study revealed neural network activity differences in oscillation power and cross-frequency coupling in the early stage of AD, providing a new perspective for developing biomarkers for early AD diagnosis.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm² microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, accounting for an estimated 60–70% of all clinically diagnosed cases worldwide. The growing focus on microglia–neuron interactions in AD research highlights their diverse, region-specific responses, which are driven by the functional and pathological heterogeneity across different brain regions. Therefore, investigating the interactions between microglia and neurons is of crucial importance. To explore the regional heterogeneity of microglia–neuron crosstalk in AD, we integrated human single-nucleus RNA sequencing data from the prefrontal cortex (PFC), hippocampus (HPC), and occipital lobe (OL) provided by the ssREAD database. Our study delineated four microglial subtypes and uncovered a pseudotime trajectory activation trajectory leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and upregulation of immune-effector and antigen-presentation programs, which collectively establish the pro-inflammatory DAM state. Furthermore, we observed that each brain region displayed unique microglia–neuron communication patterns in response to AD pathology. The PFC and OL engage a THY1-ITGAX/ITGB2 signaling axis; the HPC predominantly utilizes the PTPRM pathway. Notably, THY1 dysregulation strongly correlates with pathology in the PFC, HPC, and OL, suggesting that microglia–neuron crosstalk in AD possesses both heterogeneity and commonality. The main contribution of this study is the systematic characterization of region-specific microglia-neuron interactions and the identification of THY1 as a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions.

Neurodegenerative diseases, characterized by progressive neuronal loss and functional decline, impose a substantial global health burden. Autophagy, the principal intracellular degradative pathway for clearing misfolded proteins and damaged organelles, is vital for neuronal homeostasis, whereas maladaptive neuroinflammation is increasingly being recognized as a central driver of disease progression. A growing body of evidence indicates a bidirectional, tightly coupled relationship between autophagy and neuroinflammation: impaired autophagic flux promotes accumulation of damage-associated molecules that activate innate immune responses, while sustained inflammatory signaling further disrupts autophagy, together forming a self-reinforcing cycle that accelerates neurodegeneration. This interplay is regulated by diverse genetic, molecular, cellular, and environmental factors and manifests in cell-type-specific ways across microglia, astrocytes. Therapeutic strategies emerging from these insights include modulation of autophagic pathways (e.g., mTOR, AMPK, TFEB), targeted inhibition of inflammasome and pro-inflammatory mediators (notably NLRP3-related signaling), and delivery platforms for small molecules or nucleic acids, with increasing interest in multi-target and stage-specific interventions. This review integrates mechanistic evidence and translational advances, highlights gaps in cell-type and stage-specific understanding, and outlines priorities for developing safe, effective therapies that target the autophagy–neuroinflammation axis in neurodegenerative disorders.