Translational Neuroscience最新文献

{"title":"Association of eNOS T786C genetic polymorphism with the risk of aneurysmal subarachnoid haemorrhage.","authors":"Josip Ljevak, Kristina Gotovac Jerčić, Antonela Blažeković, David Ozretić, Ivan Perić, Nikola Blažević, Fran Borovečki, Zdravka Poljaković Skurić","doi":"10.1515/tnsci-2025-0368","DOIUrl":"https://doi.org/10.1515/tnsci-2025-0368","url":null,"abstract":"<p><strong>Background: </strong>Unruptured intracranial aneurysms (IAs) are increasingly detected due to advancements in neuroimaging. Despite improvements in treatment, aneurysmal subarachnoid haemorrhage (aSAH) is associated with high mortality and morbidity. Treatment decisions for IA are complex and individualized, considering aneurysm and patient-related risk factors. Genetic factors, particularly endothelial nitric oxide synthase (eNOS) polymorphisms, have been implicated in IA formation and rupture risk.</p><p><strong>Methods: </strong>This study investigated the association between three eNOS polymorphisms (27-bp-VNTR, T786C, and G894T) and aSAH in a cohort of 275 patients with unruptured IA or aSAH. Patients were followed for at least 8 years with clinical and imaging assessments. Genotyping of selected polymorphisms was performed, and statistical analyses were conducted to identify interactions between genetic polymorphisms and established risk factors.</p><p><strong>Results: </strong>A significant difference in the frequencies of genotypes and allele carriers of the T786C polymorphism was observed between patients with unruptured IA and those with aSAH, with an increased proportion of CC homozygotes in the aSAH group. The risk of rupture was higher in patients with the CC genotype. Multilobular aneurysms and those located in the posterior circulation had a higher incidence of rupture. Associations between arterial hypertension and certain genotypes were also found. However, no significant interaction was observed between the polymorphisms and established risk factors in relation to aneurysm rupture.</p><p><strong>Conclusion: </strong>Our data showed a significant and independent correlation between eNOS genetic polymorphism T786C and aSAH.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250368"},"PeriodicalIF":1.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of seizure prevention by cannabidiol (CBD).","authors":"Bidhan Bhandari, Sahar Emami Naeini, Sholeh Rezaee, Hannah M Rogers, Hesam Khodadadi, Asamoah Bosomtwi, Mohammad Seyyedi, Neil J MacKinnon, Krishnan M Dhandapani, Évila Lopes Salles, David C Hess, Jack C Yu, Debra Moore-Hill, Fernando L Vale, Lei P Wang, Babak Baban","doi":"10.1515/tnsci-2022-0362","DOIUrl":"10.1515/tnsci-2022-0362","url":null,"abstract":"<p><strong>Objective: </strong>Cannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study.</p><p><strong>Methods: </strong>We evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral, and injection (intraperitoneal) routes. We used CBD broad spectrum (inhaled and intraperitoneal) vs CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups.</p><p><strong>Results: </strong>Our findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested, CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (<i>p</i> < 0.05) compared to other forms of CBD treatments.</p><p><strong>Conclusion: </strong>Our data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, which warrants further research.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20220362"},"PeriodicalIF":1.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lentivirus-mediated overexpression of netrin-1/DCC co-expression promotes axonal regeneration and functional recovery in spinal cord injury via the inhibition of the NgR1-RhoA-ROCK signaling pathway.","authors":"Meng-Ling Zheng, Zheng Ma, Yuan-Xia, Li-Juan Wang, Yan Fan, Cheng-An Feng, Jian-Ping Zhou, Zhong-Ming Li, Cheng-Xing Liu, Yan-Bin XiYang, Ying-Chun Ba","doi":"10.1515/tnsci-2025-0365","DOIUrl":"https://doi.org/10.1515/tnsci-2025-0365","url":null,"abstract":"<p><p>Spinal cord injury (SCI) seriously affects the health of humans and quality of life, causing disabilities. Due to the ever-increasing traffic and cases of natural disasters, such as earthquakes, the incidence of SCI increases every year, thus causing a huge economic burden to society and patients. The lack of neurotrophic factors in the area affected by SCI and the presence of inhibitory factors for axonal regeneration are important reasons that make spinal cord regeneration and repair extremely difficult. Additionally, the correct projection of axons also plays an important role. As Netrin-1 is a signaling factor that guides axon growth, in this study, to determine whether Netrin-1 can promote axonal regeneration after binding to the receptor DCC following SCI, a Netrin-1/DCC co-expression recombinant lentiviral vector was constructed. This vector was used to assess the effect of Netrin-1 on the NgR1-RhoA-ROCK signaling pathway in an SCI model constructed in this study. Our results suggested that Netrin-1 exerts neuroprotective effects by inhibiting the NgR1-RhoA-ROCK signaling pathway after binding to its receptor DCC.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250365"},"PeriodicalIF":1.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin gallate mitigates the motor deficits in a rotenone-induced Parkinson's disease rat model via promoting protein kinase D1 and inhibiting neuronal Parthanatos.","authors":"Jianjun Wang, Yaqi Tang, Chenwu Guo, Zekun Du, Fen Chen, Shujuan Fang, Yinjuan Tang","doi":"10.1515/tnsci-2025-0366","DOIUrl":"https://doi.org/10.1515/tnsci-2025-0366","url":null,"abstract":"<p><p>Parkinson's disease (PD), a neurodegenerative disorder characterized by degeneration of the dopaminergic (DA) neurons, is still lack of available treatments to completely block neurodegeneration. (-)-Epigallocatechin-3-gallate (EGCG), a predominant active polyphenol generated from green tea, exerts multiple neuroprotective roles in the nervous system. However, the function role of EGCG in PD and the underlying mechanism remains to be investigated. In the current study, we used the rotenone injection to build the PD rat model, followed by the EGCG treatment and determined by the behavior tests, measurements of malondialdehyde, glutathione, and superoxide dismutase levels, and enzyme-linked immunosorbent assay. We revealed that, in PD rats, EGCG upregulates protein kinase D1 (PKD1) and inhibits Parthanatos to ameliorate the impaired motor function, reduce the expression of tyrosine hydroxylase, suppress the oxidative stress, and suppress the inflammation in substantia nigra. These combined results suggest that EGCG can suppress oxidative stress and inflammation to prevent DA neuron degeneration to prevent rotenone-induced motor impairments, laying the foundation for EGCG to be a novel candidate for the treatment of PD.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250366"},"PeriodicalIF":1.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related behavioural abnormalities in C57BL/6.KOR-<i>Apoe</i> ^shl mice.","authors":"Hiroshi Ueno, Yu Takahashi, Sachiko Mori, Eriko Kitano, Shinji Murakami, Kenta Wani, Tetsuji Miyazaki, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara","doi":"10.1515/tnsci-2022-0363","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0363","url":null,"abstract":"<p><p>Spontaneously hyperlipidaemic (Apoe^shl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the <i>Apoe</i> gene. However, age-related behavioural changes in commercially available Apoe^shl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer's disease (AD). To understand whether Apoe^shl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoe^shl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoe^shl mice to investigate the behavioural abnormalities associated with ageing in Apoe^shl mice. In this study, 7-month-old Apoe^shl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoe^shl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoe^shl mice showed decreased anxiety-like behaviour. Moreover, Apoe^shl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoe^shl mice changes with age. However, 11-month-old Apoe^shl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoe^shl mice can be used to investigate the function of ApoE in the central nervous system.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20220363"},"PeriodicalIF":1.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rearing in an envy-like environment increases anxiety-like behaviour in mice.","authors":"Hiroshi Ueno, Eriko Kitano, Yu Takahashi, Sachiko Mori, Shinji Murakami, Kenta Wani, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara","doi":"10.1515/tnsci-2022-0364","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0364","url":null,"abstract":"<p><p>Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy's effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20220364"},"PeriodicalIF":1.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of gradual diameter thrombectomy stent <i>in vitro</i>.","authors":"Caifeng Shen, Zhenjian Ma, Hong Li, Ming Wei","doi":"10.1515/tnsci-2022-0351","DOIUrl":"10.1515/tnsci-2022-0351","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the effect of gradient thrombectomy stent <i>in vitro</i>.</p><p><strong>Methods: </strong>The cerebrovascular fluid circulation model was made and fixed on the test table. About 0.9% sodium chloride injection was injected to the vascular model through a miniature water pump to circulate it. Four kinds of thrombus products containing different red blood cell (RBC) volumes of 0, 5, 40, and 80% were placed at the target location as thrombus. Each type of thrombus was removed five times using SOLITAIRE stent and gradient thrombectomy stent. The thrombectomy effects were observed by comparison of the two types of stents.</p><p><strong>Results: </strong>Thrombus containing 80% volume of RBC escaped thrombus fragments during thrombectomy with both stents. Thrombus containing 0% volume of RBC (rich in fibrin) had poor chimerism with stents. In the thrombus containing 0% RBC volume, there was no statistically significant difference between the two stents (<i>p</i> = 1). Thrombus removal was successful in all cases.</p><p><strong>Conclusion: </strong>The gradient thrombectomy stent is as effective as the currently used thrombectomy stent <i>in vitro</i> studies, and there is much room for improvement.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20220351"},"PeriodicalIF":1.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal mitophagy and mitochondrial health in preventing perioperative neurocognitive disorders in juvenile mice","authors":"Yan Hou, Chang Sik Yu, Feng Lv, Zhen Feng, Li Ren, Ting Li, Haoyang Fu, P.P. Li","doi":"10.1515/tnsci-2025-0385","DOIUrl":"https://doi.org/10.1515/tnsci-2025-0385","url":null,"abstract":"Abstract Objectives Rapamycin is well-known for its protection in neurodegenerative disorders, and mitochondrial dysfunction-related diseases. However, the mechanisms Rapamycin influences mitophagy in juvenile perioperative neurocognitive disorders (PND), remain poorly understood. Methods Female C57BL/6J mice (4–6 weeks) were randomly allocated to four groups: Control (C), Surgery (S), Surgery+Rapamycin (RAPA, Rapamycin 8 mg kg −1 intraperitoneally (i.p.) every other day for 7 days, 24 h before laparotomy), and Surgery+Rapamycin+3-methyladenine (3-MA+RAPA, 3-MA, 2 mg kg −1 i.p. once daily for 7 days, 1 h before Rapamycin injection). Cognitive performance was assessed on post-operative days 1, 3 and 7; hippocampal ROS, ATP, mitochondrial membrane potential, ultrastructure and mitophagy proteins were subsequently evaluated. Results PND occurred in juvenile mice following laparotomy, as evidenced by a decline in Y-maze alternation rate and novel object recognition, increased ROS levels in the hippocampus, and mitochondrial disruptions. Rapamycin protected PND by enhancing mitophagy in hippocampal neurons, reducing ROS accumulation, and preventing mitochondrial damage. Nevertheless, Rapamycin’s neuroprotective effects were abolished by 3-MA administered. Conclusions Rapamycin protects against juvenile PND by stimulating neuronal mitophagy. It offers new insights for pediatrics, but more clinical trials are needed.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.degruyterbrill.com/document/doi/10.1515/tnsci-2025-0385/pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147916233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-376a-5p ameliorates apoptosis and inflammation in lipopolysaccharide-induced intervertebral disc nucleus pulposus cells via TRAF6/NF-κB pathway","authors":"Kejie Zhang, Cong Zhang, Yuanbin Zhang","doi":"10.1515/tnsci-2025-0380","DOIUrl":"https://doi.org/10.1515/tnsci-2025-0380","url":null,"abstract":"Abstract Intervertebral disc degeneration (IDD) is a frequent chronic orthopaedic disorder. We investigated the mechanism of miR-376a-5p alleviating IDD through targeting tumor necrosis factor receptor-related factor 6 (TRAF6) to regulate the nuclear factor kappa B (NF-κB) pathway. An in vitro IDD model was established and treated with miR-376a-5p mimic, oe-TRAF6, and the NF-κB inhibitor (BAY 11–7,082). Levels of miR-376a-5p and TRAF6 mRNA, TRAF6, nucleus-p65, cytoplasm-p65 and p-p65, and inflammatory factors TNF-α, IL-1β and IL-6 were determined by RT-qPCR, Western blot, and ELISA. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry assays. The potential binding sites between miR-376a-5p and TRAF6 were predicted and verified by TargetScan database and dual-luciferase assay. LPS-induced NP cells exhibited reduced miR-376a-5p expression, up-regulated TRAF6 expression, weakened cell viability, increased apoptosis, and elevated TNF-α, IL-1β, and IL-6 levels. Overexpression of miR-376a-5p suppressed LPS-induced apoptosis and inflammatory responses and reduced nuclear translocation of p65 protein levels. There were target binding sites between miR-376a-5p and TRAF6. Overexpression of TRAF6 partially reversed the inhibitory roles of miR-376a-5p. Taken together, our study found that miR-376a-5p suppressed LPS-induced apoptosis and inflammatory response in NP cells by targeting the TRAF6/NF-κB pathway, potentially providing a new therapeutic target for IDD treatment.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.degruyterbrill.com/document/doi/10.1515/tnsci-2025-0380/pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147896104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down Syndrome: Progress in Defining Pathogenesis and Treatments for Neurodevelopmental Deficits and Alzheimer’s Disease","authors":"Renata Bartesaghi, Xu‐Qiao Chen, Aaron Johnstone, Utpal Das, William C. Mobley","doi":"10.1007/978-3-031-89307-0_19","DOIUrl":"https://doi.org/10.1007/978-3-031-89307-0_19","url":null,"abstract":"Down syndrome (DS) is a high-incidence (1:750–1000) genetic condition [93] caused by an extra copy of chromosome 21 (Chr21; HSA21) [211]. Among the various DS-linked traits, such as cardiac abnormalities and gastrointestinal disorders [49], intellectual disability (ID), which is defined by an intelligence quotient <70, is a fully penetrant phenotype [23, 223, 409] and a source of major concern to parents and relatives. In children with DS, IQ score is usually in the moderately to severely retarded range (IQ = 25–55) and decreases progressively with age [371]. Children and adults with DS exhibit deficits in a constellation of brain functions, such as memory, executive functions, language, and verbal and motor skills [62, 86, 133, 370, 371]. Understanding the nature of cognitive deficits in DS is important for understanding their biological bases, timing, and approaches to treatment. While using standardized tests, there is evidence of progressive decline, and a different pattern emerges when raw scores are examined longitudinally [133]. For example, Couzens et al. (2011), assessing raw scores for different cognitive functions, show clear increases with increasing age. Though the measures in all tests in 4-year-old children with DS were lower than in cognitively normal subjects, tests of vocabulary, comprehension, and quantitative function (so-called crystallized abilities) showed increases in performance from ages 4 through ~20 years, with apparent stabilization, or relatively modest decrements, through age 25. Interestingly, raw scores of vocabulary were stable through age ~30. In contrast, raw scores for pattern analysis (a measure of fluid ability) showed progressive improvements that continued beyond age 20. The findings show that cognitive deficits in DS are not fixed but pursue a different developmental trajectory with lesser gains relative to cognitive normals. Marked decrements linked to dementia ensue only later. Indeed, after age 40, adults with DS are at a high risk of developing Alzheimer’s disease (AD) [410]. During the past 20 years, research has made great strides in defining how trisomy of HSA21 affects cognition in early and later life. Yet, despite increasing knowledge, there are no treatments for ID or AD in DS. Herein, we discuss the efforts made to address this topic and neurobiological discoveries and insights that may lead to effective treatments.","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"1 1","pages":"331-388"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147904628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}