Kwok-Fai So

• The University of Hong Kong

Exercise training can prevent anxiety disorders in both rodent models and human cohorts. The involvement of peripheral factors in exercise‐mediated mental health is being appreciated. It is recently shown that the hepatic biosynthesis of lipocalin‐2 (LCN2) can respond to chronic restraint stress (CRS) and elicit anxiety‐like behaviors via inhibitin...

Besides surgical decompression, neuroprotection and neuroinflammation reduction are critical for acute spinal cord injury (SCI). In this study, we prepared small extracellular vesicles (sEVs) from immortalised mesenchymal stem cells overexpressing brain‐derived neurotrophic factor (BDNF) and evaluated whether intranasal administration of BDNF‐sEVs...

Aminoglycoside antibiotic‐induced sensorineural hearing loss (SNHL) is a common sensory disorder that requires the development of prophylactic and therapeutic interventions. Lycium barbarum glycopeptide (LBGP) is a peptidoglycan isolated and purified from Lycium barbarum polysaccharides that exhibit significant anti‐inflammatory, antioxidant, and n...

Physical exercise effectively prevents anxiety disorders caused by environmental stress. The neural circuitry mechanism, however, remains incomplete. Here, we identified a previously unrecognized pathway originating from the primary motor cortex (M1) to medial prefrontal cortex (mPFC) via the ventromedial thalamic (VM) nuclei in male mice. Besides...

In addition to its well-established role in vision, environmental light also plays a crucial role in non-image-forming visual functions, including the regulation of instinctive behaviors such as feeding. Clinical evidence suggests that bright light therapy can alleviate symptoms in individuals with obesity. However, the neural mechanisms underlying...

The mammalian brain has an extremely limited ability to regenerate lost neurons and to recover function following ischemic stroke. A biomaterial strategy of slowly-releasing various regeneration-promoting factors to activate endogenous neurogenesis represents a safe and practical neuronal replacement therapy. In this study, basic fibroblast growth...

Astrocytes are known to modulate synaptogenesis or neuronal activities, thus participating in mental functions. It has been shown that astrocytes are involved in the antidepressant mechanism. In this study we investigated the potential hormonal mediator governing the astrocyte-neuron interplay for stress-coping behaviors. Mice were subjected to chr...

Objective Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with limited treatment options. This study aimed to investigate the effects of Lycium barbarum extract (LBE), a Chinese herb, on the central nervous system (CNS)—including the retina, brain, and spinal cord—in 5xFAD transgenic mice after the onset of AD. Methods Sta...

Exercise enhances synaptic plasticity and alleviates depression symptoms, but the mechanism through which exercise improves high-fat diet-induced depression remains unclear. In this study, 6-week-old male C57BL/6J mice were administered a high-fat diet (HFD, 60% kcal from fat) to a HFD model for 8 weeks. The RUN group also received 1 h of daily tre...

The accumulation of α-synuclein induces neuronal loss in midbrain nuclei and leads to the disruption of motor circuits, while the pathology of α-synuclein in cortical regions remains elusive. To better characterize cortical synucleinopathy, here we generate a mouse model with the overexpression of human α-synuclein in the primary motor cortex (M1)...

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell–derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing sh...

Background Vascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the ther...

Microglia, as resident macrophages in the central nervous system, play a multifunctional role in the pathogenesis of Alzheimer’s disease (AD). Their clustering around amyloid-β (Aβ) deposits is a core pathological feature of AD. Recent advances in single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have revealed dyn...

Background Maternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD in...

Research highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusi...

JOURNAL/nrgr/04.03/01300535-202510000-00024/figure1/v/2024-11-26T163120Z/r/image-tiff The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury. However, whether it is possible to stimulate neurogenesis and reconstruct cortical layers II...

Exercise training effectively relieves anxiety disorders via modulating specific brain networks. The role of post-translational modification of proteins in this process, however, has been underappreciated. Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmil...

Alcohol abuse induces various neurological disorders including motor learning deficits, possibly by affecting neuronal and astrocytic activity. Physical exercise is one effective approach to remediate synaptic loss and motor deficits as shown by our previous works. In this study, we unrevealed the role of exercise training in the recovery of cortic...

Zeaxanthin dipalmitate (ZD) is a chemical extracted from wolfberry that protects degenerated photoreceptors in mouse retina. However, the pure ZD is expensive and hard to produce. In this study, we developed a method to enrich ZD from wolfberry on a production line and examined whether it may also protect the degenerated mouse retina. The ZD-enrich...

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions. Different mutations on a single ASD gene contribute to heterogeneity of disease phenotypes, possibly due to functional diversity of generated isoforms. SHANK2, a causative gene in ASD, demonstrates this phenomenon, but there is a scarcity of tools for studying endo...

Chronic stress induces anxiety disorders via both neural pathways and circulating factors. Although many studies have elucidated the neural circuits involved in stress-coping behaviors, the origin and regulatory mechanism of peripheral cytokines in behavioural regulation under stress conditions are not fully understood. Here, we identified a serum...

It has long been asserted that failure to recover from central nervous system diseases is due to the system’s intricate structure and the regenerative incapacity of adult neurons. Yet over recent decades, numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system, including humans’. This has challenged...

JOURNAL/nrgr/04.03/01300535-202505000-00027/figure1/v/2024-07-28T173839Z/r/image-tiff Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined...

Background Bipolar Disorder (BD), a severe neuropsychiatric condition, often manifests during adolescence. Traditional diagnostic methods, relying predominantly on clinical interviews and symptom assessments, may fall short in accuracy, especially when based solely on single-modal MRI techniques. Objective This study aims to bridge the diagnostic...

JOURNAL/nrgr/04.03/01300535-202412000-00032/figure1/v/2024-04-08T165401Z/r/image-tiff For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spi...

JOURNAL/nrgr/04.03/01300535-202410000-00030/figure1/v/2024-02-06T055622Z/r/image-tiff Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum ( L. barbarum ) polysaccharide (LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model...

Light in the environment greatly impacts a variety of brain functions, including sleep. Clinical evidence suggests that bright light treatment has a beneficial effect on stress–related diseases. Although stress can alter sleep patterns, the effect of bright light treatment on stress–induced sleep alterations and the underlying mechanism are poorly...

JOURNAL/nrgr/04.03/01300535-202404000-00037/inline-graphic1/v/2023-09-09T133047Z/r/image-tiff Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases. They also represent a potential source of transplanted cells for therapeutic applications. In vitro differentiation of functional mid...

Despite significant advancements in our understanding of addiction at the neurobiological level, a highly effective extinction procedure for preventing relapse remains elusive. In this study, we report that bright light treatment (BLT) administered during cocaine withdrawal with extinction training prevents cocaine-driven reinstatement by acting th...

JOURNAL/nrgr/04.03/01300535-202403000-00042/inline-graphic1/v/2023-08-11T153926Z/r/image-tiff Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited. Although regular exercise effectively improves learning and memory functions across multiple neurological diseases, its application in patients with epilepsy rem...

JOURNAL/nrgr/04.03/01300535-202403000-00045/inline-graphic1/v/2023-08-11T153926Z/r/image-tiff Neurotrophic keratopathy is a persistent defect of the corneal epithelium, with or without stromal ulceration, due to corneal nerve deficiency caused by a variety of etiologies. The treatment options for neurotrophic keratopathy are limited. In this study,...

JOURNAL/nrgr/04.03/01300535-202402000-00035/inline-graphic1/v/2023-07-19T141749Z/r/image-tiff Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation, differentiation, migration, and survival, as well as angiogenesis, in the context of brain injury. However, whether bioactive materials can repair the damag...

Introduction Lycium barbarum glycopeptide (LbGp) is the main bioactive compound extracted from the traditional Chinese medicine. L. barbarum berries and has been proven to have numerous health benefits, including antioxidative, anti-inflammatory, anticancer, and cytoprotective activities. However, the antiaging effect of LbGp remains unknown. Meth...

Aerobic exercise effectively ameliorates mental disorders including anxiety and depression. Current findings mainly attribute its neural mechanism to the improvement of adult neurogenesis, while leaving the possible circuitry mechanism unclear. In the current study, we identify the overexcitation of the medial prefrontal cortex (mPFC) to basolatera...

Emerging evidence suggests that there are long-term complications after recovery from COVID-19, which involve multiple systems and lead to deterioration of the quality of life. Among these different complications, male sexual dysfunction, in particular erectile dysfunction, is one of the complications being identified recently. It was initially hyp...

Background: Lycium barbarum (Wolfberry) extract has been shown to be effective in neuroprotection against aging or neural injury. Knowledge of its potential roles and biological mechanisms in relieving mental disorders, however, remains limited. Purpose: To investigate the potency of Lycium barbarum glycopeptide (LbGp) in alleviating anxiety dis...

Neural repair is highly influenced by reactive astrocytes. Atypical cadherin Celsr2 regulates neuron development and axon regeneration, while its role in glial cells remains unexplored. In this study, we show that Celsr2 is highly expressed in spinal astrocytes of adult mice, and knockout of Celsr2 results in reactive astrocytes with longer protrus...

Mesenchymal stem cells (MSCs) have shown promise for the therapy of cerebral ischemia in animal studies and clinical trials, yet their clinical application still faces many challenges. Utilizing small extracellular vesicles (sEVs) may overcome these challenges. In the study, we overexpressed brain-derived neurotrophic factor (BDNF) in cultured MSCs...

Neural decoding is useful for understanding brain functions and developing neural interface applications. However, neural interfaces based on rigid electronics often suffer from recording instability due to the foreign body responses caused by their mechanical mismatch with soft tissues, limiting the longitudinal accuracy of neural decoding methods...

Neural decoding is useful for understanding brain functions and developing neural interface applications. However, neural interfaces based on rigid electronics often suffer from recording instability due to the foreign body responses caused by their mechanical mismatch with soft tissues, limiting the longitudinal accuracy of neural decoding methods...

The aggregation of TAR DNA binding protein 43 kDa (TDP-43) is related to different neurodegenerative diseases, which leads to microglial activation and neuronal loss. The molecular mechanism driving neuronal death by reactive microglia, however, has not been completely resolved. In this study, we generated a mouse model by overexpressing mutant hum...

Salt homeostasis is orchestrated by both neural circuits and peripheral endocrine factors. The colon is one of the primary sites for electrolyte absorption, while its potential role in modulating sodium intake remains unclear. Here, we revealed that a gastrointestinal hormone, secretin, is released from colon endocrine cells under body sodium defic...

Aerobic exercise effectively relieves anxiety disorders via modulating neurogenesis and neural activity. The molecular mechanism of exercise-mediated anxiolysis, however, remains incomplete. On a chronic restrain stress (CRS) model in adolescent mice, we showed that 14-day treadmill exercise profoundly maintained normal neural activity and axonal m...

Axotomy-induced synaptic stripping modulates survival and axon regeneration of injured motoneurons. Celsr2 is supposed to mediate homophilic interactions of neighboring cells during development, and its role in synaptic stripping remains unknow. In a model of brachial plexus avulsion, Celsr2 knockout improved functional recovery, motoneuron surviva...

Background Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attr...

This 3-month randomized psychoeducation-controlled trial (RCT) of exercise was undertaken in young adolescents with subthreshold depression to examine the impact on gut microbiota. Participants (aged 12-14 years) were randomly assigned to an exercise or a psychoeducation-controlled group. The exercise intervention arm took moderate-intensity exerci...

Retinitis pigmentosa (RP) is a photoreceptor-degenerating disease with no effective treatment. Trans-corneal electrical stimulation has neuroprotective effects in degenerating retinas, but repeated applications cause corneal injury. To avoid the risk of corneal damage, here we tested whether repetitive trans-sclera electrical stimulation (TsES) pro...

[INLINE:1] Acupuncture is a medical treatment that has been widely practiced in China for over 3000 years, yet the neural mechanisms of acupuncture are not fully understood. We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation. To investigate this, we used two-photon in vivo calcium recordi...

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and prem...

Background: Elevated levels of inflammatory cytokines such as Interleukin (IL)-17A have been repeatedly linked with major depression in both animals and humans. Our recent double-blinded Randomized Placebo-controlled Trial (RCT) discovered significant efficacy of a traditional Chinese medicine substance, namely the Lycium barbarum polysaccharide (L...

Light plays an essential role in psychobiological and psychophysiological processes, such as alertness. The alerting effect is influenced by light characteristics and the timing of interventions. This meta-analysis is the first to systematically review the effect of light intervention on alertness and to discuss the optimal protocol for light inter...

A few developmental genes remain persistently expressed in the adult stage, whilst their potential functions in the mature brain remain underappreciated. Here, we report the unexpected importance of Celsr2, a core Planar cell polarity (PCP) component, in maintaining the structural and functional integrity of adult neocortex. Celsr2 is highly expres...

Innate social investigation behaviors are critical for animal survival and are regulated by both neural circuits and neuroendocrine factors. Our understandings for how neuropeptides regulate social interest, however, are incomplete at current stage. In this study, we identified the expression of secretin (SCT) in a subpopulation of excitatory neuro...

Inactivation of Celsr3 in the forebrain results in defects of longitudinal axonal tracts such as the corticospinal tract. In this study, we inactivated Celsr3 in the brainstem using En1-Cre mice ( Celsr3 cKO) and analyzed axonal and behavioral phenotypes. Celsr3 cKO animals showed an 83% reduction of rubrospinal axons and 30% decrease of corticospi...

RNA Methylation and Mental Health Aerobic exercise promotes the hepatic biosynthesis of methyl donors, which enter the brain to facilitate RNA methylation of synaptic gene transcripts. This liver‐brain axis is necessary for the prevention of anxiety‐like behaviors under environmental stress. More details can be found in article number 2105731 by Ya...

Social recognition and memory are critical for survival. The hippocampus serves as a central neural substrate underlying the dynamic coding and transmission of social information. Yet the molecular mechanisms regulating social memory integrity in hippocampus remain unelucidated. Here we report unexpected roles of Celsr2, an atypical cadherin, in re...

Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration. There is currently no effective treatment for retinitis pigmentosa. Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration, the role of lutein alone remains unclear. In this study, we admin...

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder. In preclinical models of neurological and psychiatric diseases, Lycium barbarum polysaccharide (LBP) extracted from Goji berries had anti-depressant effects including but not limited to anti-oxidative and anti-inflam...

Age-related neurodegenerative disorders such as Alzheimer's disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown t...

Physical exercise is effective in alleviating mental disorders by improving synaptic transmission; however, the link between body endurance training and neural adaptation has not yet been completely resolved. In this study, the authors investigated the role of RNA N⁶‐methyladenosine (m6A), an emerging epigenetic mechanism, in improved resilience ag...

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used...

Inactivation of Celsr3 in the forebrain results in defects of longitudinal axonal tracts such as the corticospinal tract. In this study, we inactivated Celsr3 in the brainstem using En1-Cre mice ( Celsr3 cKO) and analyzed axonal and behavioral phenotypes. Celsr3 cKO animals showed an 83% reduction of rubrospinal axons and 30% decrease of corticospi...

Light is a powerful modulator of non-visual functions. Although accumulating evidence suggests an antinociceptive effect of bright light treatment, the precise circuits that mediate the effects of light on nocifensive behaviors remain unclear. Here, we show that bright light treatment suppresses mouse nocifensive behaviors through a visual circuit...

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aβ) transform from the resting state to an M1 state and rel...

In recent years, the pharmacological benefits of herbal extracts have been revisited for their potential neuroprotective effects in glaucoma. The polysaccharides extracted from the fruits of Lycium barbarum L., or Lycium barbarum polysaccharides, exert their anti-aging effect through reducing oxidative stress, modulating the immune response, enhanc...

Drug exposure impairs cortical plasticity and motor learning, which underlies the reduced behavioral flexibility in drug addiction. Physical exercise has been used to prevent relapse in drug rehabilitation program. However, the potential benefits and molecular mechanisms of physical exercise on drug-evoked motor-cortical dysfunctions are unknown. H...

Depressed people are prone to sleep disturbance, which may in return perpetuate the depression. Both depression and sleep disturbance influence proinflammatory cytokines interleukin (IL) 6 and 1β. Thus interventions for depression should consider the effect on sleep disturbance, and vice versa. Integrative Body-Mind-Spirit (IBMS) and Qigong interve...

Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury, whereby it can inhibit microglial neurotoxicity. Therefore, luteolin holds the potential to be useful for treatment of retinal diseases. The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on...

Retinitis pigmentosa (RP) is a group of inherited photoreceptor degeneration diseases that causes blindness without effective treatment. The pathogenesis of retinal degeneration involves mainly oxidative stress and inflammatory responses. Zeaxanthin dipalmitate (ZD), a wolfberry‐derived carotenoid, has anti‐inflammatory and anti‐oxidative stress ef...

Background: The coronavirus disease 2019 (COVID-19) pandemic has been reported to have negative psychological impact on mental health. Nonetheless, there are few studies investigating the impacts on pregnant women. This study investigated the psychological impact of COVID-19 pandemic on pregnant women, and the associated risk factors that moderated...

Administration of exercise mimetic drugs could be a novel therapeutic approach to combat comorbid neurodegeneration and metabolic syndromes. Adiponectin is an adipocyte-secreted hormone. In addition to its antidiabetic effect, adiponectin mediates the antidepressant effect of physical exercise associated with adult hippocampal neurogenesis. The ant...

Background: Animal and human studies have revealed reciprocal association between exercise and gut-brain axis. However, the clinical evidence from randomized controlled trials (RCT) are still limited to directly assess the effects of aerobic exercise on gut microbiota. To fill this gap, we conducted this 12-week RCT in both groups of adolescents wi...

Although a large number of trials in the SCI field have been conducted, few proven gains have been realized for patients. In the present study, we determined the efficacy of a novel combination treatment involving surgical intervention and long-term weight-bearing walking training in spinal cord injury (SCI) subjects clinically diagnosed as complet...

Real-time ocular responses are tightly associated with emotional and cognitive processing within the central nervous system. Patterns seen in saccades, pupillary responses, and spontaneous blinking, as well as retinal microvasculature and morphology visualized via office-based ophthalmic imaging, are potential biomarkers for the screening and evalu...