Behavioral Deficits Research Articles

Extracellular signal-regulated protein kinase-2 signaling in the nucleus accumbens facilitates stress-susceptibility and cocaine reinstatement.

BackgroundSecond messenger signaling within the mesolimbic reward circuit plays a key role in the negative effects of stress and the underlying mechanisms that promote drug abuse. Since the nucleus accumbens (NAc) integrates reward valence, we investigated how extracellular signal-regulated protein kinase-2 (ERK2) signaling affects the development of stress-related comorbidities, including negative affect and drug sensitivity. MethodsWe assessed how chronic unpredictable stress (CUS) influenced the phosphorylation of ERK2-signaling proteins within the NAc of male Sprague Dawley rats. Using a herpes-simplex virus, we either upregulated or downregulated NAc ERK2 activation and evaluated behavioral responses to stress-eliciting stimuli (elevated plus maze, open field, forced-swim test) and cocaine-seeking behavior (conditioned place preference, self-administration). We also examined ERK2-mediated modifications in spine morphology of medium spiny neurons (MSNs) within the NAc. ResultsCUS increased the phosphorylation of ERK2-signaling proteins within the NAc. Viral-mediated activation of NAc ERK2 enhanced susceptibility to both depression- and anxiety-related stimuli and increased cocaine-seeking behavior (conditioned place preference and reinstatement). These behavioral changes were associated with an increase in stubby and mushroom spines of NAc MSNs. Conversely, downregulation of ERK2 activation attenuated affect-related behavioral responses in the forced swim test and blunted cocaine’s rewarding effects, without influencing NAc spine morphology. ConclusionsNAc ERK2 contributes to stress-induced behavioral deficits, including anxiety- and depression-like phenotypes, while promoting cocaine-seeking behavior. These findings suggest that ERK2 signaling in the NAc plays a role in the comorbidity of these related syndromes.

Neurotranscriptomic and behavioral effects of ISRIB, and its therapeutic effects in the traumatic brain injury model in zebrafish

Traumatic brain injury (TBI) is a global medical concern with lasting impact on brain activity and high risks of mortality. Current treatments are inadequate for repairing damaged brain cells or correcting cognitive and behavioral disabilities in patients following TBI. Mounting evidence links TBI to the activation of the integrated stress response (ISR) signaling in the brain. A novel small molecule, ISRIB, is an effective inhibitor of the ISR pathway, offering potential advantages for brain health. Here, we investigated how ISRIB affects brain transcriptome and behavior in zebrafish in a TBI model evoked by telencephalic brain injury. Overall, while TBI diminished memory and social behavior in zebrafish, administering ISRIB post-injury markedly reduced these behavioral deficits, and modulated brain gene expression, rescuing TBI-activated pathways related to inflammation and brain cell development. Collectively, this supports the role of brain ISR in TBI, and suggests potential utility of ISRIB for the treatment of TBI-related states.

Prolonged STAT1 signaling in neurons causes hyperactive behavior

The interferon (IFN)-induced STAT1 signaling pathway is a canonical immune pathway that has also been implicated in regulating neuronal activity. The pathway is enriched in brains of individuals with autism spectrum disorder (ASD) and schizophrenia (SZ). Over-activation of the STAT1 pathway causes pathological transcriptional responses, however it is unclear how these responses might translate into behavioral phenotypes. We hypothesized that prolonged STAT1 signaling in neurons would be sufficient to cause behavioral deficits associated with neurodevelopmental disorders. In this study, we developed a novel mouse model with the clinical STAT1 gain-of-function mutation, T385M, in neurons. These mice were hyperactive and displayed neural hypoactivity with less neuron counts in the caudate putamen. Driving the STAT1 gain-of-function mutation exclusively in dopaminergic neurons, which project to the caudate putamen of the dorsal striatum, mimicked some hyperactive behaviors without a reduction of neurons. Moreover, we demonstrated that this phenotype is neuron specific, as mice with prolonged STAT1 signaling in all excitatory or inhibitory neurons or in microglia were not hyperactive. Overall, these findings suggest that STAT1 signaling in neurons is a crucial player in regulating striatal neuron activity and aspects of motor behavior.

The Basis of Cognitive and Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.

To summarize and evaluate evidence pertaining to the clinical, genetic, histopathological, and neuroimaging correlates of cognitive and behavioral dysfunction in amyotrophic lateral sclerosis (ALS). We comprehensively reviewed the literature on cognitive and behavioral manifestations of ALS, narrating findings from both cross-sectional and longitudinal studies. We discussed knowledge gaps in the evidence base and key limitations affecting studies to date, before formulating a framework for future research paradigms aimed at investigating clinicopathological correlates of neuropsychological dysfunction in ALS. Studies have demonstrated clinical associations with cognitive dysfunction in ALS e.g., bulbar-onset of symptoms, pathological associations (extramotor TDP-43 deposition), and imaging associations (frontotemporal involvement). The most common behavioral deficit, apathy, is highly associated with verbal fluency, but longitudinal studies assessing behavioral dysfunction in ALS are comparatively lacking. Longitudinal studies have been helpful in identifying several potential correlates of cognitive and behavioral dysfunction but have frequently been confounded by selection bias and inappropriate testing platforms. This review provides a framework for more robust assessment of clinicopathological associations of neuropsychological abnormalities in ALS in the future, advocating for greater utilization of pre-symptomatic C9orf72 repeat expansion-carrying cohorts.

Desafios diagnósticos e terapêuticos dos transtornos de ansiedade em comorbilidade com o transtorno do espectro Autista: uma revisão integrativa

Anxiety Disorders are common in children and youth with Autism Spectrum Disorder (ASD), affecting 16-40% of cases and exacerbating functional impairment by amplifying problematic behaviours such as deficits in social skills and repetitive behaviours. The article aims to explore the interaction between ASD and Anxiety Disorders, with a focus on prevalence, diagnosis, and treatment. A literature review was conducted using databases such as Medline/PubMed, highlighting the clinical implications for managing these comorbidities. Psychopathology assessment is complex, considering underlying challenges in ASD, including atypical non-verbal responses and limitations in emotional expression, as well as the frequent overlap between anxiety and ASD symptoms. Additionally, anxiety symptoms may deviate from conventional criteria in psychopathological diagnostic manuals. Differential diagnosis between ASD and Social Anxiety is challenging due to similar symptoms. There is a demand for specific therapeutic approaches, such as modified cognitive-behavioural therapy, incorporating emotional recognition and social skills training. Pharmacological interventions require caution due to limited studies on SSRIs and potential side effects in individuals with ASD.

Bacteriophages targeting Enterococcus faecalis enhance the therapeutic efficacy of levodopa in an MPTP-induced Parkinson’s disease mouse model with E. faecalis gut colonization

Despite the intensive research on gut microbiome-associated diseases over the past 20 years, pharmacological methods for effectively eliminating pathobionts remain unsatisfactory. This study investigated the therapeutic potential of bacteriophages against Enterococcus faecalis, in which bacterial tyrosine decarboxylase (TDC) converts orally administered levodopa (L-DOPA) to dopamine, in an MPTP mouse model of Parkinson’s disease (PD). E. faecalis bacteriophages PBEF62, PBEF66, and PBEF67 (4 × 1010 PFU total/200 µl/day), and E. faecalis cells (2 × 109 CFU/200 µl/day) were orally administered at 2-h intervals before every MPTP (i.p.) and/or L-DOPA (p.o.) treatments for 13 days. The relative abundances of E. faecalis cells and bacteriophages in the feces peaked at 4 and 12 h after administration and gradually decreased by 12 and 48 h, respectively. While the administration of E. faecalis cells eliminated the beneficial effect of L-DOPA on MPTP-induced behavioral deficits, as assessed by cylinder and rotarod tests, the co-administration of bacteriophages with bacterial cells restored this effect. The modulating effects of L-DOPA, E. faecalis, and bacteriophages on PD behavior were closely associated with choline acetyltransferase expression levels in the striatum but not with tyrosine hydroxylase in the substantia nigra of each group. Recurrence and extinction of PD behaviors following treatment with E. faecalis and/or bacteriophages were also coincident with the dopamine levels in the blood and brain tissues of PD mice. The effectiveness of L-DOPA was restored after the three types of E. faecalis bacteriophages selectively eliminated E. faecalis cells, along with the TDC gene copies and transcripts responsible for converting L-DOPA to dopamine in the gastrointestinal tract. In conclusion, a combination of bacteriophages PBEF62, PBEF66, and PBEF67 targeting E. faecalis demonstrates potential as a valuable supplement to L-DOPA therapy for PD.

Mitigating aluminum chloride-induced toxicity in Drosophila melanogaster with peptide fractions from Euphorbia species

This study assessed the antioxidative and protective effects of peptide extracts from selected Euphorbia species on Aluminum Chloride (AlCl3)-induced toxicity in Drosophila melanogaster. Euphorbia humifusa (EHU), Euphorbia hirta (EHI), and Euphorbia graminae (EHG) were screened for bioactive peptides. The crude peptide extract and partially purified peptide fractions of all the plants were subjected to preliminary antioxidants activities through 2, 2-diphenyl-1-picrylhyhdrazyl (DPPH), and nitric oxide (NO) scavenging activities. The most active peptide fraction was subjected to biochemical studies using Drosophila melanogaster. Flies were treated with AlCl3 (100 mg/kg diet), peptide fraction (5 and 10 mg/kg diet), and cotreatment of AlCl3 and the fraction, respectively. After treatment, flies were homogenized for the determination of total thiol and Glutathione (non-protein thiol) content, catalase and Glutathione-S-transferase activities, and nitric oxide (nitrite/nitrate) and hydroperoxide levels. The antioxidant screening revealed that the peptide fraction from Euphorbia humifusa (PEHU) was the most significant compared to the control (ascorbic acid). The PEHU (5 and 10 mg/kg diet) maintained the redox status of the flies in the biochemical study. The PEHU significantly counteracted AlCl3-induced reduction in antioxidants (catalase, GST, GSH and Total thiol), increased nitric oxide levels, and acetylcholinesterase activity and prevented behavioral deficits flies. Hence, the peptide fraction of Euphorbia humifusa may shield against the life-threatening effects of free radicals associated with aluminum chloride toxicity.

Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents. Our analysis revealed 37 single-nucleotide variants from 36 candidate genes and over 200 CGG repeats in the FMR1 gene in one subject. The identified variants were classified as uncertain, likely pathogenic, or pathogenic based on in-silico algorithms and ACMG criteria. Notably, 52% of the identified variants were homozygous, indicating a recessive genetic architecture to ASD in this population. This finding underscores the significant impact of high consanguinity within the Qatari population, which could be utilized in genetic counseling/screening program in Qatar. We also discovered single nucleotide variants in 13 novel genes not previously associated with ASD: ARSF, BAHD1, CHST7, CUL2, FRMPD3, KCNC4, LFNG, RGS4, RNF133, SCRN2, SLC12A8, USP24, and ZNF746. Our investigation categorized the candidate genes into seven groups, highlighting their roles in cognitive development, including the ubiquitin pathway, transcription factors, solute carriers, kinases, glutamate receptors, chromatin remodelers, and ion channels.

Protective Effect of Protocatechuic Aldehyde on Cerebral Ischemia/Reperfusion Injury in Rats through Blood-Brain Barrier Protection.

Cerebral ischemia can lead to destruction of the blood-brain barrier (BBB), the main cause of cerebral edema and cerebral infarction. BBB damage is also one of the key factors affecting the result of drug therapy. We studied the protective effect of 5-day pretreatment with protocatechuic aldehyde (PAL) at doses of 10 and 20 mg/kg on BBB function and structure after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats. The infarct volume, behavioral neurological deficit score, and Evans blue content in the brain were estimated. We also evaluated the content of nitric oxide (NO) and activities of inducible and neuronal NO synthases. Expression of aquaporin-4 (AQP-4), occludin, claudin-5, and MMP-3 in the brain tissues was estimated by Western blotting. The BBB ultrastructure was analyzed under an electron microscope. We revealed that PAL at both used doses significantly reduced the neurological deficit score, brain infarct volume, and Evans blue extravasation. Electron microscopy showed that PAL significantly improved the ultrastructure of BBB and alleviated its injury. Pretreatment with PAL increased expression of occludin and claudin-5 and reduced expression of AQP-4 and MMP-3. At the same time, the release of NO and activities of NO synthases were notably inhibited. Our results suggest that PAL can be a promising compound to attenuate cerebral ischemia resulting from occlusion/reperfusion injury via BBB protection.

The brain’s structural connectivity and pre-reading abilities in young children with prenatal alcohol exposure

Children with prenatal alcohol exposure (PAE) may develop a range of neurological and behavioral deficits, including reading and language disorders. Studying the brain’s structural connectivity and its relationship to pre-reading/reading skills in young children with PAE can help understand the roots of reading deficits associated with PAE. 363 diffusion MRI scans from 135 children (114 scans from 53 children with PAE) were collected between ages 3–7 years. Children completed NEPSY-II Phonological Processing and Speeded Naming to assess pre-reading skills at each scan. Structural brain network properties were assessed in 16 regions from both hemispheres using graph theory. Linear mixed models were used to account for repeated measures within participants. Children with PAE had significantly lower pre-reading scores than unexposed children, and significantly lower graph theory metrics across bilateral reading networks. Moreover, PAE significantly moderated the associations between Phonological Processing and global efficiency and nodal degree in the bilateral and left hemisphere reading networks, such that children with PAE had stronger associations than unexposed controls. No significant associations were found for Speeded Naming. Our results suggest that brain alterations may underlie early pre-reading difficulties in children with PAE.

Enhanced Age-Dependent Motor Impairment in Males of Drosophila melanogaster Modeling Spinocerebellar Ataxia Type 1 Is Linked to Dysregulation of a Matrix Metalloproteinase

Over the past two decades, Drosophila melanogaster has proven to be successful in modeling the polyglutamine (polyQ) (caused by CAG repeats) family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. In this study, pan-neuronal expression of human Ataxin-1 with long polyQ repeat of 82 amino acids was driven using an elav-GAL4 driver line. This would essentially model the polyQ disease spinocerebellar ataxia type 1 (SCA1). Longevity and behavioral analysis of male flies expressing human Ataxin-1 revealed compromised lifespan and accelerated locomotor activity deficits both in diurnal activity and negative geotaxis response compared to control flies. Interestingly, this decline in motor response was coupled to an enhancement of matrix metalloproteinase 1 (dMMP1) expression together with declining expression of extracellular matrix (ECM) fibroblast growth factor (FGF) signaling by hedgehog (Hh) and branchless (bnl) and a significant decrease in expression of survival motor neuron gene (dsmn) in old (30 d) flies. Taken together, our results indicate a role for dysregulation of matrix metalloproteinase in polyQ disease with consequent impact on ECM signaling factors, as well as SMN at the neuromuscular junction causing overt physiological and behavioral deficits.

Nasal obstruction during development leads to defective synapse elimination, hypersynchrony, and impaired cerebellar function

Nasal respiratory disorders are linked to craniofacial anomalies and systemic dysfunctions. However, the implications of nasal respiratory disorders on brain development and their subsequent impact on brain functionalization remain largely unknown. Here, we describe that nasal obstruction from postnatal developmental stages in mice precipitates deficits in cerebellum-associated behaviors and compromised refinement and maturation of neural circuits in the cerebellum. We show that mice with nasal obstruction during developmental phases exhibit marked impairments in motor function and exhibit increased immobility time in forced swimming test. Additionally, we identified critical periods during which nasal respiration is essential for optimizing motor function and preserving mental health. Our study also reveals that nasal obstruction in mice disrupts the typical developmental process of synapse elimination in the cerebellum and hinders the normal transition of activity patterns in cerebellar Purkinje cell populations during development. Through comparing activity patterns in mouse models subjected to nasal obstruction at various stages, we suggest that the maturation of specific activity pattern among Purkinje cell populations is fundamental to the functional integrity of the cerebellum. Our findings highlight the indispensable role of adequate nasal respiration during development for the establishment and functional integrity of neural circuits, thereby significantly affecting brain function.

Gray Matter Volume Correlates of Co-Occurring Depression in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) involves neurodevelopmental syndromes with significant deficits in communication, motor behaviors, emotional and social comprehension. Often, individuals with ASD exhibit co-occurring depression characterized by a change in mood and diminished interest in previously enjoyable activities. Due to communicative challenges and a lack of appropriate assessments in this cohort, co-occurring depression can often go undiagnosed during routine clinical examinations and, thus, its management neglected. The literature on co-occurring depression in adults with ASD is limited. Therefore, understanding the neural basis of the co-occurring psychopathology of depression in ASD is crucial for identifying brain-based markers for its timely and effective management.Using structural MRI and phenotypic data from the Autism Brain Imaging Data Exchange (ABIDE II) repository, we examined the pattern of relationship regional grey matter volume (rGMV) has with co-occurring depression and autism severity within regions of a priori interest in adults with ASD (n = 44; age = 17-28 years). Further, we performed an exploratory analysis of the rGMV differences between ASD and matched typically developed (TD, n = 39; age = 18-31 years) samples. The severity of co-occurring depression correlated negatively with the rGMV of the right thalamus. Additionally, a significant interaction was evident between the severity of co-occurring depression and core ASD symptoms towards explaining the rGMV in the left cerebellum crus II. The results further the understanding of the neurobiological underpinnings of co-occurring depression in adults with ASD towards exploring neuroimaging-based biomarkers in the same cohort.

The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Aβ clearance in Alzheimer’s disease mouse model

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that causes cognitive dysfunction in older adults. One of the AD pathological factors, β-Amyloid (Aβ), triggers inflammatory responses and phagocytosis of microglia. C-type lectin domain family 5 member A (CLEC5A) induces over-reactive inflammatory responses in several virus infections. Yet, the role of CLEC5A in AD progression remains unknown. This study aimed to elucidate the contribution of CLEC5A to Aβ-induced microglial activation and behavioral deficits.MethodsThe AD mouse model was crossed with Clec5a knockout mice for subsequent behavioral and pathological tests. The memory deficit was revealed by the Morris water maze, while the nociception abnormalities were examined by the von Frey filament and hotplate test. The Aβ deposition and microglia recruitment were identified by ELISA and immunohistochemistry. The inflammatory signals were identified by ELISA and western blotting. In the Clec5a knockdown microglial cell model and Clec5a knockout primary microglia, the microglial phagocytosis was revealed using the fluorescent-labeled Aβ.ResultsThe AD mice with Clec5a knockout improved Aβ-induced memory deficit and abnormal nociception. These mice have reduced Aβ deposition and increased microglia coverage surrounding the amyloid plaque, suggesting the involvement of CLEC5A in AD progression and Aβ clearance. Moreover, the phagocytosis was also increased in the Aβ-stressed Clec5a knockdown microglial cell lines and Clec5a knockout primary microglia.ConclusionThe Clec5a knockout ameliorates AD-like deficits by modulating microglial Aβ clearance. This study implies that targeting microglial Clec5a could offer a promising approach to mitigate AD progression.

Membrane Associated RNA-Containing Vesicles Regulate Cortical Astrocytic Microdomain Calcium Transients in Awake Ischemic Stroke Mice.

Astrocytic processes minutely regulate neuronal activity via tripartite synaptic structures. The precision-tuning of the function of astrocytic processes is garnering increasing attention because of its significance in promoting brain repair following ischemic stroke. Microdomain calcium (Ca2+) transients in astrocytic processes are pivotal for the functional regulation of these processes. However, the understanding of the alterations and regulatory mechanism of microdomain Ca2+ transients during stroke remains limited. In the present study, a fast high-resolution, miniaturized two-photon microscopy is used to show that the levels of astrocytic microdomain Ca2+ transients are significantly reduced in the peri-infarct area of awake ischemic stroke mice. This finding correlated with the behavioral deficits shown by these mice under freely-moving conditions. Mitochondrial Ca2+ activity is an important factor driving the microdomain Ca2+ transients. DEAD Box 1 (DDX1) bound to circSCMH1 (a circular RNA involved in vascular post-stroke repair) facilitates the formation of membrane-associated RNA-containing vesicles (MARVs) and enhances the activity of astrocytic microdomain Ca2+ transients, thereby promoting behavioral recovery. These results show that targeting astrocytic microdomain Ca2+ transients is a potential therapeutic approach in stroke intervention.

Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region.

Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (As2O3) in the mouse striatal region. Healthy adult male mice were chronically administered with varying concentrations of As2O3 (2, 4 and 8mg/kg bw) alone and along with CUR (100mg/kg bw) orally for 45days.Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations. Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 and 8mg/kg bw) and curcumin (100mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As2O3 (4 and 8mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment. Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As2O3-induced behavioral deficits, as well as biochemical and morphological alterations.

Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) may be associated with cerebral vasospasm, which can lead to delayed cerebral ischemia, infarction, and worsened functional outcomes. The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Secondary ischemic injury in SAH is associated with increased extracellular glutamate, which can overactivate NMDA receptors (NMDARs), thereby triggering NMDAR-mediated cellular damage. In this study, we have evaluated the effect of the pH-sensitive GluN2B-selective NMDAR inhibitor, NP10679, on neurologic impairment after SAH. This compound demonstrates a selective increase in potency at the acidic extracellular pH levels that occur in the setting of ischemia. We found that NP10679 produced durable improvement of behavioral deficits in a well-characterized murine model of SAH, and these effects were greater than those produced by nimodipine alone, the current standard of care. In addition, we observed an unexpected reduction in SAH-induced luminal narrowing of the middle cerebral artery. Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. Based on allometric scaling of both toxicological and efficacy data, the therapeutic margin in man should be at least 2. These results further demonstrate the utility of pH-dependent neuroprotective agents and GluN2B-selective NMDAR inhibitors as potential therapeutic strategies for the treatment of aSAH. Significance Statement This report describes the properties and utility of the GluN2B-selective pH-sensitive NMDA receptor inhibitor, NP10679, in a well-characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage, and that in rats there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication.

Bound phenolics extracts of jujube peel relieve cadmium-induced toxicity by reducing lipid accumulation of Caenorhabditis elegans.

To investigate the effect of bound phenolics extracts (BPEs) of jujube peel on relieving cadmium (Cd)-induced toxicity and its mechanism, the behavioral deficits, lipid accumulation, and fatty acid synthesis-related gene expression in Caenorhabditis elegans in Cd exposure group and BPEs improvement groups were determined and compared. The results showed that BPEs significantly improved Cd-induced behavioral deficits in C. elegans, and no significant differences could be found in low-dose (12.5µg/mL) and high-dose (100µg/mL) BPEs improvement groups. The treatment of BPEs effectively improved intestinal injury and lipofuscin and lipid accumulation. Especially, oil red O staining intensity in C. elegans treated with BPEs at 50µg/mL was reduced by 12.60%. BPEs significantly controlled the increase in content of C16:0, C16:1, C18:0, C18:1, and C18:2 induced by Cd by regulating the lipid accumulation in Escherichia coli OP50. Cd exposure induced lipid accumulation in C. elegans by upregulating oleic acid synthesis-related gene expression in E. coli OP50. Furthermore, BPEs treatment significantly downregulated the fatty acid synthesis-related gene expression in C. elegans and E. coli OP50. This research could reveal the mechanism of BPEs of jujube peel in relieving Cd-induced toxicity and provide a theoretical basis for the development of functional foods rich in polyphenols. PRACTICAL APPLICATION: Jujube peel, a by-product of jujube processing, is usually discarded due to its coarse texture. However, jujube peel has been proven to possess abundant polyphenols, polysaccharides, and cyclic adenosine phosphate. In addition, in our previous research, bound phenolics extracts (BPEs) of jujube peel were found to perform better in lowering lipid accumulation than that of free phenolics extracts. This study further investigate the effect of BPEs of jujube peel on relieving Cd-induced toxicity and its mechanism on the base of our previous research. It could realize the comprehensive utilization of by-products of jujube processing.

Transforming lives in autism spectrum disorder treatment through acupuncture: A case report

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, restricted and repetitive behaviors, and narrow interests. Given the high prevalence of ASD and the lack of specific pharmacological treatments, there is a pressing need for alternative therapeutic approaches. Acupuncture has shown promise in improving the clinical symptoms of ASD. This report presents the case of a 6-year-old girl diagnosed with ASD, intellectual developmental disorder, attention deficit hyperactivity disorder, and articulation disorder. She underwent Liu’s pediatric neurological rehabilitation acupuncture therapy (PNRAT) for over 2 years. The treatment involved specific scalp acupuncture techniques targeting cognitive and linguistic rehabilitation. After the treatment course, the patient showed significant improvements in cognitive, linguistic, social, and behavioral symptoms, transitioning from limited verbal communication and marked social difficulties to thriving in a mainstream school setting. This case highlights the potential of Liu’s PNRAT as an effective intervention for ASD. The observed improvements suggest that acupuncture may offer valuable therapeutic benefits for children with ASD, contributing to the growing interest in its potential as an adjunct therapy. Further research is needed to optimize treatment protocols and explore synergies with conventional therapies.

A new 2-hit model combining serine racemase deletion and maternal separation displays behavioral and cognitive deficits associated with schizophrenia

Schizophrenia (SCZ) is a multifactorial psychotic disorder characterized by positive and negative symptoms as well as cognitive impairments. To advance the current treatments, it is important to improve animal models by considering the multifactorial etiology, thus by combining different risk factors. The objective of our study was to explore in a new mouse model, the impact of genetic deletion of serine racemase (genetic vulnerability) combined with an early stress factor induced by maternal separation (early environmental exposure) in the context of SCZ development. The face validity of the model was assessed through a wide range of behavioral experiments. The 2-hit mice displayed an increased locomotor activity mimicking positive symptoms, working memory impairment, cognitive deficits and recognition memory alterations, which could reflect neophobia. This new multifactorial model therefore presents an interesting phenotype for modelling animal model with partial behavioral and cognitive deficits associated with SCZ.