a-dual-color-fiber-photometry-method-for-recording-astrocyte-neuron

A Dual-Color Fiber Photometry Method for Recording Astrocyte-Neuron Activity Across Multiple Brain Regions During Learning and Memory Behaviors

Learning and memory depend critically on the coordination between neurons and astrocytes across distributed brain regions. Astrocytes modulate synaptic ...

Third Military Medical University

Epidemiological data from the Center of Disease Control (CDC) and the World Health Organization (WHO) statistics in 2017 show that 10.0 million people around the world became sick with tuberculosis.  (MTB) is an intracellular parasite that mainly attacks macrophages and inhibits their apoptosis. It can become a long-term infection in humans, causing a series of pathological changes and clinical manifestations. In this review, we summarize innate immunity including the inhibition of antioxidants, the maturation and acidification of phagolysosomes and especially the apoptosis and autophagy of macrophages. Besides, we also elaborate on the adaptive immune response and the formation of granulomas. A thorough understanding of these escape mechanisms is of major importance for the prevention, diagnosis and treatment of tuberculosis.

The Immune Escape Mechanisms of .

 Alzheimer's disease (AD) is the most common dementia, characterized by significant cognitive impairments and neural network dysfunction. Currently, multiple therapeutic strategies are being developed to design effective anti-AD drugs. Among them, Withaferin A (WA), a natural steroidal lactone extracted from Withania somnifera leaves, has been shown to reduce amyloid-β (Aβ) peptide levels in vitro. However, its potential to improve cognitive function in AD remains unclear.  In this study, 5xFAD mice were administered WA (2 mg/kg intraperitoneally every 2 days) for 14 days, and its neuroprotective effects were evaluated through behavioral tests, wide-field imaging, immunohistochemistry, and ELISA.  WA significantly improved short-term memory, as evidenced by enhanced performance in the Novel Object Recognition Test (NORT) ( < 0.001,  = 10), Novel Location Recognition Test (NLRT) ( < 0.01,  = 14), and Three-Chamber Social Test (TCST) ( < 0.001,  = 8). WA also ameliorated long-term memory deficits in the Morris Water Maze Test (MWMT) ( < 0.05,  = 7). Furthermore, cortical wide-field Ca imaging revealed that WA treatment rescued slow-wave impairments by enhancing long-range coherence (0.8363 ± 0.0185,  < 0.01,  = 8) and reducing the frequency of slow-wave activity (0.6578 ± 0.0512 Hz,  < 0.01,  = 8). Additionally, WA treatment significantly reduced Aβ plaque deposition in both cortical and hippocampal regions.  These findings suggest that WA may be a promising therapeutic agent for AD, exerting neuroprotective effects.

Withaferin A Rescues Brain Network Dysfunction and Cognitive Deficits in a Mouse Model of Alzheimer's Disease.

The astrocyte-neuron network in the primary somatosensory cortex (S1) responds dynamically to pain stimuli and plays a pivotal role in pain processing. These stimuli activate astrocytic α7-nicotinic acetylcholine receptors (α7-nAChRs), yet their contribution to pain perception remains largely unclear. This study investigates the role of astrocytic α7-nAChRs in pain information processing and perception. Astrocytic α7-nAChRs were selectively deleted by injecting rAAV5-GfaABCD-NLS-Cre-P2A-mCherry into the S1 region of LoxP-Chrna7 transgenic mice or by tamoxifen administration in ALDH1-CreERT2:Chrna7 mice. Immunohistochemistry was used to assess the expression of α7-nAChR and gliotransmitter d-serine. Astrocytic Ca transients were monitored in vivo using two-photon Ca imaging following AAV5-GfaABCD-cytoGCaMP6f-SV40 labeling. Neuronal Ca transients in S1 evoked by plantar electric shock were recorded via fiber photometry in freely moving mice. Nociceptive and sensory behaviors were evaluated using hot plate and von Frey tests. Statistical analyses included Welch's t-tests for normally distributed data, Mann-Whitney U tests for non-normal data, and two-way ANOVA. Results showed that conditional deletion of α7-nAChRs in astrocytes markedly reduced d-serine levels within astrocytic territories. Two-photon Ca imaging and fiber photometry revealed that α7-nAChR deletion attenuated both astrocytic Ca transients and footshock-evoked neuronal Ca activity in S1. Behaviorally, thermal pain responses were significantly impaired, whereas tactile thresholds and open-field behaviors were unaffected. These findings identify astrocytic α7-nAChRs in S1 facilitate d-serine levels and enhance astrocytic activity. Their physiological function is essential for pain-related information processing within astrocyte-neuron networks and plays a critical role in regulating pain perception.

Astrocytic α7-nicotinic acetylcholine receptors mediate pain information processing and perception.

Spatial exploration is fundamental to the construction of internal cognitive maps, yet the mechanisms underlying its fine-scale microstructural disruption in Alzheimer's disease (AD) remain elusive. The medial entorhinal cortex layer II (MECII) serves as a critical hub for spatial navigation, where norepinephrine (NE) signaling modulates astrocyte activity to shape neuronal network dynamics. In this study, we combined fine-grained behavioral quantification with simultaneous in vivo dual-color fiber photometry to investigate astrocyte-neuronal coupling in the MECII of APP/PS1 transgenic mice. We report that AD mice exhibit a distinct fragmented exploration phenotype, characterized by frequent but transient sniffing and rearing bouts, which coincides with a profound loss of temporal synchronization between MECII astrocytes and neurons. Notably, pharmacological activation of the noradrenergic axis using the highly selective α-adrenergic receptor (αAR) agonist A61603 successfully re-established astrocyte-neuronal network coupling across behavioral states. This intervention significantly ameliorated the fragmented exploration phenotype without altering general locomotor activity. These findings identify disrupted astrocyte-neuronal temporal coordination in the MECII as a pivotal physiological mechanism driving spatial exploration deficits in AD, suggesting that restoring αAR signaling represents a promising therapeutic strategy for early AD-related cognitive dysfunction.

α-adrenergic receptor activation ameliorates fragmented spatial exploration by improving astrocyte-neuronal coupling in the medial entorhinal cortex of Alzheimer's disease mice.

Article	Year
The Immune Escape Mechanisms of . International journal of molecular sciences\| PubMed ID: 30650615	2019
Withaferin A Rescues Brain Network Dysfunction and Cognitive Deficits in a Mouse Model of Alzheimer's Disease. Pharmaceuticals (Basel, Switzerland)\| PubMed ID: 40573212	2025
Astrocytic α7-nicotinic acetylcholine receptors mediate pain information processing and perception. Neurobiology of disease\| PubMed ID: 41453579	2026
α-adrenergic receptor activation ameliorates fragmented spatial exploration by improving astrocyte-neuronal coupling in the medial entorhinal cortex of Alzheimer's disease mice. Neurobiology of disease\| PubMed ID: 41997460	2026

Fengjuan Wu

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