Febrile seizures are the most common childhood paroxysmal neurological disorder. Although ilepcimide is used for pediatric epilepsy, its efficacy in febrile seizures remains unknown. Here, we investigated the effects and mechanisms of ilepcimide in a juvenile mouse model of febrile seizures using network pharmacology, molecular docking, brain slice electrophysiology and patch-clamp recordings of transfected cells. Ilepcimide prolonged seizure latency and reduced EEG spike-wave frequency. Network pharmacology linked its targets to glutamatergic synaptic signaling. Molecular docking further predicted that ilepcimide could target two subunits of AMPA receptor. In acute hippocampal slices, ilepcimide suppressed CA1 pyramidal neuron firing, increased rheobase, and prolonged action potential half-width. In HEK293T cells expressing GluA1/GluA2, it prolonged AMPAR deactivation and desensitization time constants. These results suggest that ilepcimide protects against febrile seizures through a multi-faceted mechanism: modulation of glutamatergic transmission, reduction of hippocampal excitability, and altered AMPA receptor gating. This study offers new target predictions and experimental evidence supporting the extended use of ilepcimide in pediatric febrile seizures.
Pruritus, commonly known as itch, is a protective somatosensory sensation whose dysregulation is a common feature of many pathologic conditions and can severely impact quality of life. Despite its clinical relevance, itch perception is among the least well known of all somatosensory modalities. G protein coupled receptors (GPCRs) in pruritic circuits are key modulators of itch, however the intracellular regulators of GPCR signaling in itch circuits remain largely unexplored. Regulators of G protein signaling (RGS) proteins are vital modulators of GPCR signaling and may influence itch processing in histaminergic and non-histaminergic circuits. Here we report that RGS6, a member of the R7 RGS protein family, modulates itch through both histaminergic and non-histaminergic mechanisms in female mice. Using global knockout mouse models, we show that this anti-pruritic phenotype is specific to RGS6, with no comparable effect in RGS7, highlighting functional specificity within the R7 RGS family. This study uncovers a regulatory role of RGS6 in modulating pruritus in females and provides critical insights into mechanisms fundamental to acute and pathological itch.
Mesenchymal stem cell (MSC)-derived exosomes are promising mediators of neuroregeneration, but their functional heterogeneity remains incompletely understood. We investigated whether parental-cell passage and vesicle integrity influence the characteristics and biological activity of exosomes derived from human umbilical cord-derived MSCs (hUC-MSCs). hUC-MSC identity was confirmed by spindle-shaped morphology and flow cytometric analysis demonstrating high expression of CD73, CD90, and CD105 together with minimal expression of CD34 and CD45. Exosomes isolated from passages 1 (P1), 3 (P3), and 5 (P5) were characterized by nanoparticle tracking analysis (NTA), fluorescence NTA, scanning electron microscopy, and Western blotting. Their biological effects were evaluated in Neuro-2a (N2A) cells by immunofluorescence analysis of βIII-tubulin, MAP2, and NeuN together with the CCK-8 assay. P1-derived exosomes were associated with increases in neuronal-associated marker expression, neurite-like morphology, and CCK-8 metabolic activity, whereas heat-treated exosomes exhibited attenuated biological activity. These findings indicate that parental-cell passage and vesicle integrity influence the biological activity of hUC-MSC-derived exosomes and highlight the importance of standardized MSC characterization, passage control, and exosome quality assessment for the development of reproducible neuroregenerative products.
Olfactory stimulation with volatile terpenes has been associated with modulation of human brain activity; however, sex-dependent neurophysiological responses to terpene-derived aromas remain unclear. This study investigated cortical responses to orange- and pine-derived terpene aromas using relative spectral power analysis of electroencephalography (EEG) rhythms and standardized low-resolution electromagnetic tomography (sLORETA). Volatile and odor-active compounds were characterized using an electronic nose (E-nose) and gas chromatography-mass spectrometry-olfactometry (GC-MS-O), indicating terpene-dominant profiles in both aroma samples. EEG recordings were obtained before, during, and after aroma inhalation. Significant sex-dependent differences in cortical responses were observed. In males, orange aroma induced significant increases in relative beta- and gamma-band power, particularly in the temporal and occipital regions. In females, pine aroma produced a significant increase in relative beta-band power, mainly in the frontal and occipital regions. sLORETA analysis further revealed distinct cortical activation patterns associated with aroma type and sex. These findings indicate that terpene-based olfactory stimulation differentially modulates cortical EEG responses in males and females, providing neurophysiological evidence for sex-dependent processing of olfactory stimuli.
The auditory brainstem response (ABR) is widely used to assess auditory function, yet the effects of click duration on ABR morphology remain unclear. Using a spiking neuronal network model of the auditory brainstem, we simulated responses to clicks ranging from 0.1 to 2 ms. The model predicted that prolonged click duration selectively alters wave V, while earlier waves (I-IV) remain stable. We validated these predictions with ABR recordings from Mongolian gerbils (Meriones unguiculatus) under matched stimulus conditions, confirming that the wave V amplitude and the wave IV-V interval changed systematically with longer clicks. These results suggest that early ABR waves, generated by auditory nerve and lower brainstem nuclei, primarily reflect onset synchrony and are insensitive to temporal broadening, whereas wave V, originating from higher brainstem structures such as the inferior colliculus, reflects temporal integration and is selectively influenced by stimulus envelope. Results from this combined modeling and experimental approach clarify the role of click duration in shaping ABR morphology, and additionally validate the predictive power of the modeling approach.
The Asc-1/SLC7A10 transporter regulates extracellular levels of the NMDA receptor co-agonists glycine and D-serine, yet its role at excitatory synapses in the brainstem remains poorly understood. We investigated how pharmacological Asc-1 blockade modulates NMDA receptor-mediated synaptic transmission at hypoglossal motoneurons and whether glycine or D-serine is the functionally dominant co-agonist at these synapses. Whole-cell patch-clamp recordings were performed in Mg2+-free ACSF from hypoglossal motoneurons in brainstem slices of neonatal mice. Bath application of the selective Asc-1 inhibitor BMS-466442 (10 µM) significantly increased NMDA receptor-mediated mEPSC amplitude and tonic holding current, without affecting mEPSC frequency. Exogenous glycine (1 mM) robustly potentiated mEPSC amplitude and frequency both in the absence and presence of BMS-466442, whereas D-serine selectively increased tonic holding current in an Asc-1-dependent manner. Three-way ANOVA confirmed a significant co-agonist type × condition interaction, with glycine more effective than D-serine at potentiating phasic synaptic responses. These findings identify Asc-1 as a regulator of NMDA receptor co-agonist availability at brainstem excitatory synapses and suggest that glycine, rather than D-serine, is the dominant synaptic co-agonist at mouse hypoglossal motoneurons.
Fetal Alcohol Spectrum Disorders (FASD) describe a range of neurobiological and behavioral changes following prenatal alcohol exposure. Previous work has shown that moderate prenatal alcohol exposure (mPAE) can produce alterations to GABAergic neurotransmission in the hippocampal formation (HPF) as well as morphological alterations in GABAergic interneuron expression in adult rats. In the present study, we tested the hypothesis that mPAE differentially alters GABAA subunit protein expression in dorsal and ventral HPF of naïve adult male and female Long-Evans control and mPAE rats. We focused our attention on the α1, α4, and α5 subunits as they have relatively high densities within the hippocampus and have been linked to hippocampal-dependent learning and memory. Membrane fractions were collected from dorsal and ventral HPF, and western blots were performed to detect levels of GABAA α1, α4, and α5 subunit protein expression. Overall, we did not detect prenatal treatment group differences suggesting that mPAE does not result in differential GABAA subunit protein expression in dorsal or ventral HPF of male and female rats. However, the results revealed significantly greater protein expression for α4 and α5 subunits in the dorsal HPF. GABAA α1 protein expression did not vary significantly across the dorsal and ventral HPF. Our findings support the general conclusion that GABAA subunit protein expression in the HPF reflects intrinsic regional specialization of GABAergic signaling rather than effects of mPAE.
Neurodegenerative disease risk following traumatic brain injury (TBI) has been associated with vascular abnormalities and brain inflammation. However, the extent to which diffuse TBI with at least one persistent neurological deficit contributes to chronic neurodegeneration is not well understood. In this study, we investigated the impact of experimental diffuse TBI on the cerebral vasculature in the CA1 region of the hippocampus, which is vulnerable to multiple cognitive-associated neurodegenerative diseases. At 6-months post-injury, a timepoint with known cognitive impairment, we employed laser capture microdissection (LCM) to isolate parenchymal blood vessels from the CA1 subregion of the hippocampus in Sprague-Dawley rats subjected to either sham or midline fluid percussion injury. LCM vessels were processed for RNA sequencing and differentially expressed gene (DEG) analyses (DESeq2) were performed, followed by pathway enrichment analysis using genes with a log2FC > 0 and p-value < 0.05. A subset of differentially expressed genes (9%) were associated with microtubule/cytoskeletal organization, including the PLEC gene (encoding plectin) (Log2FC=+9.5, p < 0.0001), a cytoskeletal protein that maintains tissue integrity and whose overexpression has recently been identified as a risk factor for Alzheimer's disease (AD). Pathway analyses showed the most upregulated and downregulated biological pathways were involved in neurodegeneration-multiple-diseases (Gene count 11, p-adjusted < 0.01) and AD (Gene count 8, p-adjusted < 0.04). Understanding the complex interplay between TBI, the cerebral vasculature, and neurodegeneration risk is critical for prognosis and interventions that mitigate the long-term effects of brain injury and improve outcomes for patients.
AIMS:This study evaluates the impacts of p-coumaric acid in the challenging condition of diabetic neuropathy, within a focus on Kv7 channel-mediated mechanisms. METHODS:Rats were rendered diabetic by intravenous STZ (50 mg/kg, n = 8). p-Coumaric acid (25, 50, or 100 mg/kg) was given per oral for 28 days. Behavioral testing included von Frey and Hargreaves assays. Blood glucose levels were measured at multiple time points. Primary dorsal root ganglion neurons were collected and utilized for whole-cell patch-clamp recordings to assess M-type (Kv7) K+ currents. RT-PCR was utilized to quantify KCNQ2 and KCNQ5 mRNA expressions. KEY FINDINGS:p-Coumaric acid dose-dependently lowered blood glucose, with the 50 mg/kg group providing optimal effect. All doses significantly altered mechanical and thermal hypersensitivity. At 50 mg/kg, it increased M-type K+ current density and amplitude and enhanced Kv7 activation. RT-PCR revealed increased channel mRNA expressions. CONCLUSIONS:p-Coumaric acid dose-dependently reduces hyperglycemia, alters allodynia and hyperalgesia, and enhances M-type Kv7 function in dorsal root ganglion neurons. By enhancing Kv7 current density, activation, and mRNA expressions, it was associated with changes in Kv7 channel activity that may influence neuronal excitability. These findings suggest that the metabolic and electrophysiological effects of PCA, including its potential modulation of Kv7-related mechanisms, warrant further investigation in diabetic neuropathy. SIGNIFICANCE STATEMENT:This study shows that p-coumaric acid alters diabetic neuropathic pain by enhancing Kv7 channel function in sensory neurons, highlighting Kv7 modulation as a key mechanism in peripheral nerve excitability and a potential therapeutic target.
BACKGROUND:Major depressive disorder (MDD) is highly prevalent and often complicated by anxiety symptoms, yet the neurobiological features associated with anxious depression remain incompletely characterized. The amygdala-prefrontal cortex (PFC) circuit, central to affect regulation, has been implicated in anxious depressive symptoms. METHODS:We recruited 40 MDD patients and 69 healthy controls (HCs) from Tianjin Anding Hospital. All participants underwent resting-state functional magnetic resonance imaging(fMRI) and clinical assessments. Seed-based functional connectivity (FC) analyses were performed using the bilateral amygdala based on the Automated Anatomical Labeling (AAL) atlas. Group comparisons, partial correlations, and regression analyses tested associations between amygdala-based FC and HDRS-17 symptom dimensions, with subgroup analyses distinguishing MDD patients with and without anxiety. RESULTS:Compared with HCs, MDD patients exhibited reduced FC between the right amygdala and prefrontal cortex, including the right middle frontal gyrus (MFG) and the left inferior frontal gyrus, triangular part (IFGtri) (GRF: voxel-level p < 0.001, cluster-level p < 0.05). Within the MDD group, higher right amygdala-MFG FC values were associated with HDRS-17 symptoms, including total scores and depressive and somatic symptom dimensions (r = 0.393, p = 0.020; r = 0.360, p = 0.033; r = 0.351, p = 0.039, uncorrected p). In exploratory subgroup analyses, right amygdala-MFG FC showed a positive association with HDRS-17 scores in MDD patients with anxiety (R2 = 0.280, F = 8.957, p = 0.006, Beta = 0.529, t = 2.993, p = 0.006); however, the FC × anxiety subgroup interaction did not reach statistical significance. CONCLUSION:Our findings identify disrupted right amygdala-MFG connectivity as a potential neural correlate of symptom heterogeneity in MDD, particularly in patients with anxiety symptoms.
Germline deletion of the core circadian transcription factor Bmal1 has been shown to reduce blood-spinal cord barrier (BSCB) disruption and tissue loss following moderate T9 contusive spinal cord injury (SCI) in mice. Therefore, effects of conditional Bmal1 deletions were tested using the same model. A strong reduction of Bmal1 expression in the brain or spinal cord followed tamoxifen treatment of Bmal1loxp/loxp young adult mice who carried the broadly expressed Cag-CreERT2 recombinase transgene. Supporting functional consequences of such a deficit, canonical BMAL1 target genes Nr1d1 and Dbp were also downregulated. However, only few tissue damage markers were moderately reduced at 3 days post SCI. Furthermore, neither locomotor recovery nor long-term white matter sparing was improved. Similar SCI phenotype was observed in endothelia-selective Bmal1-/- mice (Cdh5-Cre:Bmal1loxp/loxp) including modest attenuation of few acute injury markers, but no significant effects on functional recovery or long-term tissue sparing. These data suggest that germline deletion of Bmal1 is protective against SCI due to compensatory changes in gene expression that originate during development and involve cells beyond endothelia. Therefore, a direct role for BMAL1 in secondary injury cascades that are activated after SCI is unlikely.
T-2 toxin is a widely distributed environmental mycotoxin that poses severe neurotoxic risks to humans and animals. Neuroinflammatory responses constitute a key mechanism underlying the neurotoxicity of T-2 toxin. However, its molecular mechanisms for inducing inflammatory responses in the nervous system remain incompletely understood. This study investigated the role of B-cell translocation gene 2 (BTG2) in T-2 toxin-induced microglial activation and evaluated the neuroprotective potential of resveratrol (Res). In vivo experiments demonstrated that exposure to T-2 toxin resulted in spatial learning, memory impairments and locomotor deficits in mice. These behavioral phenotypes were accompanied by neuroinflammation in the hippocampus and cerebral cortex, characterized by microglial activation and the upregulation of BTG2. Res pre-treatment effectively reversed these neurobehavioral deficits and suppressed the neuroinflammatory response. Mechanistic analyses revealed that Res considerably alleviated T-2 toxin-induced TLR4/MyD88/NF-κB pathway activation. In vitro studies using BV-2 microglial cells confirmed these findings. Notably, siRNA-mediated knockdown of BTG2 also abolished TLR4 pathway activation and subsequent cytokine expression induced by T-2 toxin, establishing BTG2 as a critical upstream regulator. Furthermore, RNA sequencing systematically verified that BTG2 regulates the immune response network, specifically targeting the TLR4 cascades. Collectively, these findings provide novel evidence that Res may target the BTG2-regulated TLR4/MyD88/NF-κB signal pathway to exert neuroprotection, providing a promising intervention option for reducing the environmental and health hazards associated with exposure to T-2 toxin.
Central sensitization in the spinal dorsal horn, characterized by enhanced neuronal excitability and sustained neuroinflammatory responses, is a key mechanism underlying persistent inflammatory pain; however, the upstream molecular regulators coordinating these processes remain incompletely understood. In this study, a mouse model of inflammatory pain was established by intraplantar injection of complete Freund's adjuvant (CFA), and lentiviral short hairpin RNA was used to knock down phosphatase of regenerating liver-1 (PRL-1) in the spinal dorsal horn. CFA-induced inflammatory pain was associated with persistent mechanical hypersensitivity and increased PRL-1 expression in spinal neurons. PRL-1 knockdown attenuated pain hypersensitivity and was accompanied by reduced expression of the N-methyl-D-aspartate receptor subunit GluN2B. In addition, PRL-1 knockdown was associated with decreased microglial reactivity and lower levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Together, these findings suggest that PRL-1 is associated with inflammatory pain and spinal neuronal sensitization and neuroinflammatory responses.
The Na+,K + -ATPase (NKA) enzyme is crucial for maintaining neuronal excitability, yet its response to acute physical exertion in the central nervous system remains largely unexplored. Here, we report a volume-dependent modulation of NKA activity in the cerebral cortex of rats subjected to a strenuous swimming protocol. A single bout of exhaustive exercise (1 set) significantly decreased total NKA activity and increased blood-brain barrier (BBB) permeability (albumin extravasation) without altering lipid peroxidation. Conversely, repeated exposure (3 sets, 72-h intervals) triggered an acute compensatory response: it prevented BBB disruption and significantly upregulated total NKA, α1, and α2/3 isoform activities. This functional upregulation occurred independently of total NKA protein expression but was accompanied by increased p-PKC/PKC and p-CaMKII/CaMKII phosphorylation ratios. These findings indicate that while an initial bout of exhaustive exercise compromises cortical NKA activity and neurovascular integrity, recurrent acute exertion induces rapid neuroprotective and enzymatic adaptations driven by post-translational kinase signaling.
Neuritin 1 (NRN1) is a neurotrophic factor known to protect neurons from damage and cell death; however, its role and mechanism in cervical spinal cord injury (CSCI) remain unclear. In this study, we investigated the function of NRN1 using oxygen-glucose deprivation (OGD)-treated PC12 cells and a rat model of CSCI established by anterior cervical screw compression. In vitro, NRN1 overexpression promoted neurite outgrowth, attenuated oxidative stress, and inhibited apoptosis in OGD‑exposed PC12 cells, while NRN1 knockdown showed opposite results. Mechanistically, co-immunoprecipitation and immunofluorescence confirmed that NRN1 interacts with FZD2. In OGD-treated PC12 cells, overexpression of FZD2 reversed the neuronal damage induced by NRN1 silencing, reducing oxidative stress and the number of apoptotic cells. Furthermore, NRN1‑mediated neuroprotection was dependent on activation of the GSK‑3β/Nrf2 pathway, since pharmacological inhibition of Nrf2 with ML385 abrogated the protective effects of NRN1. In vivo, decreased expression of NRN1 was observed at the site of spinal cord injury in rats. Notably, intramedullary delivery of adeno‑associated virus (AAV) encoding NRN1 restored NRN1 levels, significantly improved motor function, reduced neuronal apoptosis, and alleviated oxidative stress in spinal cord tissue. Collectively, our findings demonstrate that NRN1 exerts neuroprotective effects against CSCI by binding to FZD2 and activating the GSK‑3β/Nrf2 signaling pathway, suggesting that targeting NRN1 may represent a novel therapeutic strategy for promoting motor recovery in CSCI patients.
BACKGROUND:The olfactory system plays a critical role in modulating social cognition, with the anterior piriform cortex (aPC) serving as a key hub. However, the specific contribution of aPC pyramidal neurons to social regulation remains poorly understood. METHODS:In this study, we selectively silenced these neurons in C57BL/6J mice using a genetic apoptosis approach. TUNEL staining confirmed the specific loss of targeted neurons in the experimental group. The buried food test and the Go/No-Go odor discrimination assay were used to verify the effects of aPC pyramidal neuron apoptosis on the olfactory ability of mice. The three-chamber social test was used to assess the sociability and social novelty recognition ability of mice. The open field test was used to assess the locomotor ability and anxiety level of mice. RESULTS:Buried food and Go/No-Go odor discrimination assays revealed deficits in both olfactory sensitivity and complex odor discrimination. Results from three-chamber tests indicated that while basic sociability remained intact, social novelty recognition was significantly impaired. Notably, no impairments in anxiety or motor function were observed. CONCLUSIONS:These findings demonstrate that aPC pyramidal neurons are essential for mediating olfactory discrimination and social novelty recognition, identifying them as a core node within the olfactory-social cognition circuit and a potential therapeutic target for interventions addressing social cognitive impairments.
Xylazine, a veterinary anesthetic, is an adulterant in fentanyl and heroin that worsens opioid-related adverse effects. Two recent evidences - one epidemiological and the other pharmacological - have emerged regarding xylazine. Epidemiologically, xylazine co-use with methamphetamine (METH) is increasing; for example, in a recent toxicology report, xylazine was detected in 30% of human METH samples. Pharmacologically, xylazine is not only an α2-adrenoceptor agonist but also a full κ-opioid receptor agonist. Here, we determined effects of xylazine (1, 2.5, 5 mg/kg) on METH (1 mg/kg)-induced hyperlocomotion and investigated α2-adrenoceptor and κ-opioid receptor mechanisms. Hyperlocomotion was selected because it is a well-characterized preclinical effect of METH. In METH-naïve rats, xylazine transiently reduced locomotor activity. For co-administration with METH, xylazine dose-dependently reduced hyperlocomotion evoked by METH. In rats pretreated with the α2-adrenoceptor antagonist yohimbine (1 mg/kg), xylazine did not reduce METH-induced hyperlocomotion. Pretreatment with the competitive κ-opioid receptor antagonist LY2456302 (30 mg/kg) also attenuated xylazine's suppression of METH-induced hyperlocomotion. In xylazine-naïve rats, neither LY2456302 (30 mg/kg) or yohimbine (1 mg/kg) affected METH-evoked hyperlocomotion or spontaneous locomotor activity. Our results show that METH-evoked hyperlocomotion is sensitive to κ-opioid and α2-adrenergic receptor activity and suggest both receptor systems contribute to xylazine's in vivo pharmacological profile.
Parkinson’s disease (PD) is characterized by progressive dopaminergic neuron loss and motor and non-motor impairments. Mitochondrial dysfunction and altered post-translational modifications, including SUMOylation, have emerged as key mechanisms in PD pathogenesis. Here, we investigated global SUMOylation changes in in vivo and in vitro PD models induced by MPTP and MPP+, respectively. Intranasal MPTP administration in rats induced region- and time-dependent changes in Ubc9 and SENP3 across the olfactory bulb, prefrontal cortex, striatum, and hippocampus. In primary cortical neurons, MPP+ reduced SUMO-2/3 conjugation, Ubc9 and SENP3 levels, along with the mitochondrial fission proteins Drp1 and Mff. Notably, SENP3 showed opposite regulation in vivo and in vitro, highlighting model-specific SUMOylation responses to neurotoxic stress. These findings suggest that context-dependent alterations in SUMOylation and mitochondrial dynamics contribute to PD pathogenesis.
Experiences such as sensing a presence, feeling as if insects were crawling under the skin and related phenomena have been described in psychiatric, neurological, and toxicological contexts. However, they also occur frequently in the general population. Previous research suggests that stable physiological traits may predispose individuals to complex bodily hallucinations. The present exploratory study therefore examined whether resting-state electrocortical oscillatory activity is associated with proneness to such experiences. Participants from the general population completed the Complex Bodily Hallucinatory Experiences Scale (CBHES) prior to undergoing a brief eyes-closed resting-state EEG recording. Correlation clusters between CBHES scores and oscillatory activity were analyzed across the entire scalp, without any a priori hypotheses regarding frequency bands or localization. Significant correlations were found only within three left-lateralized clusters in the delta frequency range: the middle insula, which is involved in interoceptive bodily awareness; the superior anterior temporal lobe, which is associated with representations of animate intentional agents; and the orbitofrontal cortex, which is involved in affective touch processing, self-referential cognition, and reality monitoring. Together, these findings suggest that complex bodily hallucinations involve at least these functional properties and engage multiple cognitive mechanisms. They further suggest that intrinsic oscillatory activity in resting-state EEG constitutes a candidate neurophysiological correlate of proneness to such experiences.
Neurodegeneration is a hallmark of Niemann-Pick disease type C1 (NPC1). One component in the pathology of neurodegeneration is increased lysosomal membrane permeability, especially in microglia. Leakage of lysosomal proteases, such as cathepsin B, into the cytoplasm and ultimately into the interstitial space can lead to activation of apoptosis and neuroinflammation. In line with previous reports showing the involvement of cathepsin B in neurodegeneration and the benefit of inhibiting cathepsin B to prevent neurodegeneration, we tested whether disease severity would be reduced in NPC1 mutant mice devoid of cathepsin B. Contrary to our expectation, the double mutant mice exhibited a more severe disease phenotype as measured by disease severity phenotypic scoring, beam walk latency test and a reduction in life expectancy. This highlights the importance of cathepsin B during postnatal development in the context of NPC1.
