Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Early-life stress (ELS) is a major contributor to neurodevelopmental vulnerability, particularly within the dentate gyrus (DG), where oxidative burden and microglial activation disrupt adult neurogenesis. Here, we examined whether N-acetylcysteine (NAC), a cysteine prodrug and glutathione precursor, could counteract impaired neurogenesis induced by neonatal maternal separation (NMS). Adolescent NAC administration restored the number of Ki67 + proliferating progenitors and DCX + immature neurons in the DG of NMS rats, accompanied by reduced reactive oxygen species, suppressed iNOS induction, and attenuated microglial activation. NAC also normalized EAAC1 expression, indicating enhanced neuronal antioxidant capacity. Notably, NAC rescued diminished neurogenesis in EAAC1 knockout mice, demonstrating its efficacy under both stress-induced and transporter-deficient redox imbalance. These findings identify NAC as a potent modulator of hippocampal neuroplasticity, acting through the restoration of redox and inflammatory homeostasis, and support its potential as an early therapeutic strategy to mitigate long-lasting neurodevelopmental consequences of ELS.

Astrocytes have been known to support neuronal function, but until now, memory storage and recall has thought to be largely controlled by neurons. In this article, we shed light on recent research published by Williamson et al. that, for the first time, shows astrocytes to participate in memory formation and recall.

Astrocytes have been known to support neuronal function, but until now, memory storage and recall has thought to be largely controlled by neurons. In this article, we shed light on recent research published by Williamson et al. that, for the first time, shows astrocytes to participate in memory formation and recall.

Astrocytes have been known to support neuronal function, but until now, memory storage and recall has thought to be largely controlled by neurons. In this article, we shed light on recent research published by Williamson et al. that, for the first time, shows astrocytes to participate in memory formation and recall.

Astrocytes have been known to support neuronal function, but until now, memory storage and recall has thought to be largely controlled by neurons. In this article, we shed light on recent research published by Williamson et al. that, for the first time, shows astrocytes to participate in memory formation and recall.

In the auditory system, the spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from inner supporting cells (ISCs). This ATP release sets off a cascade, activating purinergic autoreceptors, opening of Ca 2+ -activated Cl- channel TMEM16A, Cl- efflux and osmotic cell shrinkage. Then, the shrunken ISCs efficiently regain their original volume, suggesting the existence of mechanisms for refilling Cl- and K + , priming them for subsequent activity. This study explores the potential involvement of NKCCs (Na+ -K+ -Cl- cotransporters) and KCCs (K+ -Cl- cotransporters) in ISC spontaneous activity, considering their capability to transport both Cl- and K+ ions across the cell membrane. Employing a combination of immunohistochemistry, pharmacological interventions, and shRNA experiment, we unveiled the pivotal role of NKCC1 in cochlear spontaneous activity. Immunohistochemistry revealed robust NKCC1 expression in ISCs, persisting until the 2nd postnatal week. Intriguingly, we observed a developmental shift in NKCC1 expression from ISCs to synaptophysin-positive efferent terminals at postnatal day 18, hinting at its potential involvement in modulating synaptic transmission during the post-hearing period. Experiments using bumetanide, a well-known NKCC inhibitor, supported the functional significance of NKCC1 in ISC spontaneous activity. Bumetanide significantly reduced the frequency of spontaneous extracellular potentials (sEP) and spontaneous optical changes (sOCs) in ISCs. NKCC1-shRNA experiments conducted in cultured cochlear tissues further supported these findings, demonstrating a substantial decrease in event frequency and area. Taken together, we revealed the role of NKCC1 in shaping the ISC spontaneous activity that govern auditory pathway development.

Bestrophin-1 (BEST1) is a Ca2+ -activated anion channel known for its role in astrocytes. Best1 is permeable to gliotransmitters, including GABA, to contribute to tonic GABA inhibition and modulate synaptic transmission in neighboring neurons. Despite the crucial functions of astrocytic BEST1, there is an absence of genetically engineered cell-type specific conditional mouse models addressing these roles. In this study, we developed an astrocyte-specific BEST1 conditional knock-out (BEST1 aKO) mouse line. Using the embryonic stem cell (ES cell) targeting method, we developed Best1 floxed mice (C57BL/6JCya-Best1em1flox /Cya), which have exon 3, 4, 5, and 6 of Best1 flanked by two loxP sites. By crossing with hGFAP-CreERT2 mice, we generated Best1 floxed/hGFAP-CreERT2 mice, which allowed for the tamoxifen-inducible deletion of Best1 under the human GFAP promoter. We characterized its features across various brain regions, including the striatum, hippocampal dentate gyrus (HpDG), and Parafascicular thalamic nucleus (Pf). Compared to the Cre-negative control, we observed significantly reduced BEST1 protein expression in immunohistochemistry (IHC) and tonic GABA inhibition in patch clamp recordings. The reduction in tonic GABA inhibition was 66.7% in the striatum, 46.4% in the HpDG, and 49.6% in the Pf. Our findings demonstrate that the BEST1 channel in astrocytes significantly contributes to tonic inhibition in the local brain areas. These mice will be valuable for future studies not only on tonic GABA release but also on tonic release of gliotransmitters mediated by astrocytic BEST1.

Obesity is a growing health concern, mainly caused by poor dietary habits. Yet, accurately tracking the diet and food intake of individuals with obesity is challenging. Although 3D motion capture technology is becoming increasingly important in healthcare, its potential for detecting early signs of obesity has not been fully explored. In this research, we used a deep LSTM network trained with individual identity (identity-trained deep LSTM network) to analyze 3D time-series skeleton data from mouse models with diet-induced obesity. First, we analyzed the data from two different viewpoints: allocentric and egocentric. Second, we trained various deep recurrent networks (e.g., RNN, GRU, LSTM) to predict the identity. Lastly, we tested whether these models effectively encode obese-like motion representations by training a support vector classifier with the latent features from the last layer. Our experimental results indicate that the optimal performance is achieved when utilizing an identity-trained deep LSTM network in conjunction with an egocentric viewpoint. This approach suggests a new way to use deep learning to spot health risks in mouse models of obesity and should be useful for detecting early signs of obesity in humans.

Astrocytes primarily maintain physiological brain homeostasis. However, under various pathological conditions, they can undergo morphological, transcriptomic, and functional transformations, collectively referred to as reactive astrogliosis.Recent studies have accumulated lines of evidence that reactive astrogliosis plays a crucial role in the pathology of Alzheimer’s disease (AD). In particular, monoamine oxidase B, a mitochondrial enzyme mainly expressed in astrocytes, significantly contributes to neuronal dysfunction and neurodegeneration in AD brains. Moreover, it has been reported that reactive astrogliosis precedes other pathological hallmarks such as amyloid-beta plaque deposition and tau tangle formation in AD.Due to the early onset and profound impact of reactive astrocytes on pathology, there have been extensive efforts in the past decade to visualize these cells in the brains of AD patients using positron emission tomography (PET) imaging. In this review, we summarize the recent studies regarding the essential pathological importance of reactive astrocytes in AD and their application as a target for PET imaging.