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1.
Nanomaterials (Basel) ; 14(18)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39330640

RESUMO

Presently, ethylene oxide (EtO) is posing a significant threat to both human health and the environment due to occasional or deliberate emissions. However, few works so far have focused on this issue. It is urgent to explore novel and effective technology to protect against the threat of EtO. Herein, a series of AC/ZSM-5 composites were prepared to improve the adsorption performance for EtO, evaluated by dynamic breakthrough experiments. Particularly, the AC/ZSM-20% composite demonstrated a more excellent adsorption capacity of 81.9 mg/g at 25 °C and 50% RH than that of pristine AC and ZSM-5 with 32.5 and 52.3 mg/g, respectively. Moreover, the adsorption capacity of the AC/ZSM-20% composite remained constant even after five adsorption-desorption cycles. The adsorption mechanism of EtO on the composite is further revealed by density functional theory (DFT) calculations.

2.
J Clin Neurosci ; 129: 110853, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39348790

RESUMO

Spinal disorders pose a significant global health challenge, affecting nearly 5% of the population and incurring substantial socioeconomic costs. Over time, spinal neurosurgery has evolved from basic 19th-century techniques to today's minimally invasive procedures. The recent integration of technologies such as robotic assistance and advanced imaging has not only improved precision but also reshaped treatment paradigms. This review explores key innovations in imaging, biomaterials, and emerging fields such as AI, examining how they address long-standing challenges in spinal care, including enhancing surgical accuracy and promoting tissue regeneration. Are we at the threshold of a new era in healthcare technology, or are these innovations merely enhancements that may not fundamentally advance clinical care? We aim to answer this question by offering a concise introduction to each technology and discussing in depth its status and challenges, providing readers with a clearer understanding of its actual potential to revolutionize surgical practices.

3.
Int J Surg ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913424

RESUMO

Surgical resection is essential for treating solid tumors, with success largely dependent on the complete excision of neoplastic cells. However, neurosurgical procedures must delicately balance tumor removal with the preservation of surrounding tissue. Achieving clear margins is particularly challenging in cases like glioblastoma due to the limitations of traditional white light visualization. These limitations often result in incomplete resections, leading to frequent recurrences, or excessive resection that harms vital neural structures, causing iatrogenic nerve damage which can lead to sensory and functional deficits. Current statistics reveal a 90% recurrence rate for malignant gliomas. Similarly, an 8% incidence of iatrogenic nerve trauma contributes to an estimated 25 million cases of peripheral nerve injury globally each year. These figures underscore the urgent need for improved intraoperative techniques for lesion margin and nerve identification and visualization. Recent advances in neurosurgical imaging, such as fluorescence-guided surgery (FGS), have begun to address these challenges. Fluorescent agents used in FGS illuminate target tissues, although not all do so selectively. Despite the promising results of agents such as 5-aminolevulinic acid and indocyanine green, their applications are mainly limited by issues of sensitivity and specificity. Furthermore, these agents do not effectively address the need for precise nerve visualization. Nerve Peptide 41, a novel systemically administered fluorescent nerve-targeted probe, shows promise in filling this gap. This review assesses the major fluorescent imaging modalities in neurosurgery, highlighting each of their benefits, limitations, and potential.

4.
Neurosurg Rev ; 47(1): 152, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605210

RESUMO

Background- Postoperative delirium is a common complication associated with the elderly, causing increased morbidity and prolonged hospital stay. However, its risk factors in chronic subdural hematoma patients have not been well studied. Methods- A total of 202 consecutive patients with chronic subdural hematoma at Peking University Third Hospital between January 2018 and January 2023 were enrolled. Various clinical indicators were analyzed to identify independent risk factors for postoperative delirium using univariate and multivariate regression analyses. Delirium risk prediction models were developed as a nomogram and a Markov chain. Results- Out of the 202 patients (age, 71 (IQR, 18); female-to-male ratio, 1:2.7) studied, 63 (31.2%) experienced postoperative delirium. Univariate analysis identified age (p < 0.001), gender (p = 0.014), restraint belt use (p < 0.001), electrolyte imbalance (p < 0.001), visual analog scale score (p < 0.001), hematoma thickness (p < 0.001), midline shift (p < 0.001), hematoma side (p = 0.013), hematoma location (p = 0.018), and urinal catheterization (p = 0.028) as significant factors. Multivariate regression analysis confirmed the significance of restraint belt use (B = 7.657, p < 0.001), electrolyte imbalance (B = -3.993, p = 0.001), visual analog scale score (B = 2.331, p = 0.016), and midline shift (B = 0.335, p = 0.007). Hematoma thickness and age had no significant impact. Conclusion- Increased midline shift and visual analog scale scores, alongside restraint belt use and electrolyte imbalance elevate delirium risk in chronic subdural hematoma surgery. Our prediction models may offer reference value in this context.


Assuntos
Delírio do Despertar , Hematoma Subdural Crônico , Humanos , Masculino , Feminino , Idoso , Hematoma Subdural Crônico/complicações , Delírio do Despertar/complicações , Estudos Retrospectivos , Fatores de Risco , Medição de Risco , Eletrólitos
5.
Ann Clin Transl Neurol ; 11(5): 1325-1337, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38644648

RESUMO

OBJECTIVE: To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE. METHODS: Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed. RESULTS: In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%). INTERPRETATION: The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.


Assuntos
Encefalite , Doença de Hashimoto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Encefalite/imunologia , Encefalite/diagnóstico , Encefalite/terapia , Adulto , Idoso , Doença de Hashimoto/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Doenças Autoimunes do Sistema Nervoso/terapia , Adulto Jovem , Autoanticorpos/sangue , Adolescente , Encefalite Límbica/imunologia , Encefalite Límbica/diagnóstico , Encefalite Límbica/terapia , Imunoterapia/métodos
6.
Neurol Sci ; 45(9): 4481-4492, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38523205

RESUMO

INTRODUCTION: This study was designed to analyze clinical and radiographic features of adult patients coexisting with NMDAR-IgG and MOG-IgG. METHODS: Eleven adult patients coexisting with NMDAR-IgG and MOG-IgG were collected from Xiangya Hospital, Central South University, between June 2017 and December 2021. Fifty-five patients with anti-NMDAR encephalitis and 49 with MOG-AD were served as controls. RESULTS: Onset age was 27 (IQR 20-34) years old. Seizures and psychotic symptoms were prominent symptoms. Ten of eleven patients presented abnormal T2/FLAIR hyperintensity, mainly involving the cortex, brainstem, and optic nerve. Compared with the NMDAR IgG ( +)/MOG IgG ( -) group, the NMDAR IgG ( +)/MOG IgG ( +) group showed more ataxia symptoms (27.3% vs. 3.6%, P = 0.037), while more T2/FLAIR hyperintensity lesions were found in the brainstem (54.5% vs. 7.3%, P < 0.001) and optic nerve (27.3% vs. 1.8%, P = 0.011) with more abnormal MRI patterns (90.9% vs. 41.8%, P = 0.003). In comparison with the NMDAR IgG ( -)/MOG IgG ( +) group, the NMDAR IgG ( +)/MOG IgG ( +) group had more seizures (72.7% vs. 24.5%, P = 0.007) and mental symptoms (45.5% vs. 0, P < 0.001). The NMDAR IgG ( +)/MOG IgG ( +) group tended to be treated with corticosteroids alone (63.6% vs. 20.0%, P = 0.009), more prone to recur (36.5% vs. 7.3%, P = 0.028) and lower mRS score (P = 0.036) at the last follow-up than pure anti-NMDAR encephalitis. CONCLUSION: The symptoms of the NMDAR IgG ( +)/MOG IgG ( +) group were more similar to anti-NMDAR encephalitis, while MRI patterns overlapped more with MOG-AD. Detecting both NMDAR-IgG and MOG-IgG maybe warranted in patients with atypical encephalitis symptoms and demyelinating lesions in infratentorial regions.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Autoanticorpos , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Humanos , Adulto , Masculino , Feminino , Glicoproteína Mielina-Oligodendrócito/imunologia , Imunoglobulina G/sangue , Adulto Jovem , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Autoanticorpos/sangue , Imageamento por Ressonância Magnética , Receptores de N-Metil-D-Aspartato/imunologia , Pessoa de Meia-Idade
7.
J Exp Clin Cancer Res ; 43(1): 47, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342925

RESUMO

In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Células Supressoras Mieloides , Humanos , Glioma/patologia , Glioblastoma/patologia , Imunoterapia , Imunomodulação , Microambiente Tumoral , Neoplasias Encefálicas/tratamento farmacológico
8.
J Zhejiang Univ Sci B ; 24(9): 796-806, 2023.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37701956

RESUMO

Oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck, ranks sixth worldwide in terms of cancers with the most negative impact, owing to tumor relapse rates, cervical lymphnode metastasis, and the lack of an efficacious systemic therapy. Its prognosis is poor, and its mortality rate is high. Octamer-binding transcription factor 4 (OCT4) is a member of the Pit-Oct-Unc (POU) family and is a key reprogramming factor that produces a marked effect in preserving the pluripotency and self-renewal state of embryonic stem cells (ESCs). According to recent studies, OCT4 participates in retaining the survival of OSCC cancer stem cells (CSCs), which has far-reaching implications for the occurrence, recurrence, metastasis, and prognosis of oral carcinogenesis. Therefore, we summarize the structure, subtypes, and function of OCT4 as well as its role in the occurrence, progression, and prognosis of OSCC.

9.
J Cancer Res Clin Oncol ; 149(16): 15127-15141, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37633867

RESUMO

BACKGROUND: Parotid gland carcinoma (PGC) is a rare but aggressive head and neck cancer, and the prognostic model associated with survival after surgical resection has not yet been established. This study aimed to construct a novel postoperative nomogram and risk classification system for the individualized prediction of overall survival (OS) among patients with resected PGC. METHODS: Patients with PGC who underwent surgery between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were randomized into training and validation cohorts (7:3). A nomogram developed using independent prognostic factors based on the results of the multivariate Cox regression analysis. Harrell's concordance index (C-index), time-dependent area under the curve (AUC), and calibration plots were used to validate the performance of the nomogram. Moreover, decision curve analysis (DCA) was performed to compare the clinical use of the nomogram with that of traditional TNM staging. RESULTS: In this study, 5077 patients who underwent surgery for PGC were included. Age, sex, marital status, tumor grade, histology, TNM stage, surgery type, radiotherapy, and chemotherapy were independent prognostic factors. Based on these independent factors, a postoperative nomogram was developed. The C-index of the proposed nomogram was 0.807 (95% confidence interval 0.797-0.817). Meanwhile, the time-dependent AUC (> 0.8) indicated that the nomogram had a satisfactory discriminative ability. The calibration curves showed good concordance between the predicted and actual probabilities of OS, and DCA curves indicated that the nomogram had a better clinical application value than the traditional TNM staging. Moreover, a risk classification system was built that could perfectly classify patients with PGC into three risk groups. CONCLUSIONS: This study constructed a novel postoperative nomogram and corresponding risk classification system to predict the OS of patients with PGC after surgery. These tools can be used to stratify patients with high or low risk of mortality and provide high-risk patients with more directed therapies and closer follow-up.


Assuntos
Carcinoma , Nomogramas , Humanos , Glândula Parótida/cirurgia , Área Sob a Curva , Calibragem , Programa de SEER
10.
Nat Commun ; 14(1): 1880, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019936

RESUMO

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.


Assuntos
Transtorno Depressivo Maior , Habenula , Camundongos , Animais , Masculino , Habenula/fisiologia , Adenosina/farmacologia , Neurônios/metabolismo , Hipotálamo/metabolismo , Receptor A2A de Adenosina/metabolismo
11.
Brain Sci ; 13(2)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36831912

RESUMO

Glutamic acid decarboxylase (GAD) antibody-related encephalitis is an autoimmune disease associated with intracellular neuronal antigens. We report on a rare case of GAD antibody-associated encephalitis complicated with focal segmental stiffness-person syndrome (SPS) in a middle-aged woman. The disease course lasted for >10 years, initially presenting with drug-resistant epilepsy, followed by stiffness of the right lower limb, and right upper limb involvement. The patient experienced anxiety and depression symptoms due to long-term illness. During hospitalization, serum and cerebrospinal fluid GAD antibodies were positive and no tumor was found. The symptoms were significantly relieved after corticosteroid therapy and intravenous immunoglobulin immunomodulation therapy. To the best of our knowledge, this case is the first to discuss the early recognition and treatment of chronic epilepsy and focal segmental SPS caused by anti-GAD antibody-related encephalitis.

12.
Am J Hum Genet ; 109(10): 1932-1943, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36206744

RESUMO

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was available (six out of eight probands), and human genetic datasets suggest that FRMD5 is intolerant to loss of function (LoF). We found that the fly ortholog of FRMD5, CG5022 (dFrmd), is expressed in the larval and adult central nervous systems where it is present in neurons but not in glia. dFrmd LoF mutant flies are viable but are extremely sensitive to heat shock, which induces severe seizures. The mutants also exhibit defective responses to light. The human FRMD5 reference (Ref) cDNA rescues the fly dFrmd LoF phenotypes. In contrast, all the FRMD5 variants tested in this study (c.340T>C, c.1051A>G, c.1053C>G, c.1054T>C, c.1045A>C, and c.1637A>G) behave as partial LoF variants. In addition, our results indicate that two variants that were tested have dominant-negative effects. In summary, the evidence supports that the observed variants in FRMD5 cause neurological symptoms in humans.


Assuntos
Deficiência Intelectual , Animais , Ataxia/genética , DNA Complementar , Deficiências do Desenvolvimento/genética , Movimentos Oculares , Humanos , Deficiência Intelectual/genética , Proteínas de Membrana , Fosfatidilinositóis , Convulsões , Proteínas Supressoras de Tumor/genética
13.
Front Genet ; 12: 777630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970303

RESUMO

Hailey-Hailey disease (HHD) is a rare autosomal-dominant blistering disorder characterized by recurrent vesicular and erosive lesions at intertriginous sites. We described a 24-year-old male who presented with multiple bright red verrucous papules in his mons pubis, bilateral groins, scrotum, perineum, and crissum, clinically resembling condyloma acuminatum. The histopathology showed extensive acantholysis with the characteristic appearance of a dilapidated brick-wall. The mutation analysis revealed a novel splice-site mutation in the ATP2C1 gene. The patient was definitely diagnosed with HHD. The antibacterial treatments resulted in a dramatic improvement. Our findings help to broaden the understanding of clinical manifestations of HHD and improve the clinical diagnosis and treatment of this disease.

14.
ACS Appl Mater Interfaces ; 13(1): 233-244, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33373178

RESUMO

Photodynamic therapy (PDT) and photothermal therapies (PTTs) are both promising strategies for effective tumor therapy. However, the absence of O2 at tumor sites hinders the sustained response of photosensitizers. Here, we develop a recycled cerium oxide (CeO2) catalase nanozyme-loaded hyaluronic acid nanovesicle to address the hypoxic tumor microenvironments and targeted delivery of the photosensitizers [indocyanine green (ICG)] to tumors. A polysaccharide complex effectively modifies the surface of a polyethylenimine phenylboronic acid nanostructure to achieve the CeO2 nanozyme-loading nanovesicles that exhibit both tumor-targeted enhancement and an improved hypoxic microenvironment. Also, the hydrogen peroxide responsiveness and acid-sensitive cleavage of phenylboronic acid specifically disintegrate the ICG/nanozyme coloaded nanovesicles in the tumor microenvironment. The in vitro synergistic tests and tumor suppression rate tests indicated that the cerium oxide nanozyme significantly improves the outcomes of PDT via cerium-element valence state recycling and hypoxia improvement, thus enhancing the tumor suppression efficiency. This pH/H2O2-responsive nanozyme/ICG codelivery system provides a good carrier model for improving the tumor microenvironment and increasing the efficiency of tumor-targeted PTT and PDT therapies.


Assuntos
Antineoplásicos/uso terapêutico , Cério/uso terapêutico , Verde de Indocianina/uso terapêutico , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Catálise , Linhagem Celular Tumoral , Cério/química , Cério/toxicidade , Feminino , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Neoplasias/metabolismo , Fotoquimioterapia , Terapia Fototérmica , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
15.
Fitoterapia ; 143: 104549, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32173420

RESUMO

Eight new flavonoids daemoflavans A-H, including two dimeric proanthocyanidins (1 and 2), four flavans (3-6), two 2-arylbenzofurans (7 and 8), along with nine known compounds (9-17), were isolated from the fruit of Daemonorops draco. Their structures, including the absolute configurations, were elucidated by extensive spectroscopic data, ECD analysis, and X-ray crystal diffraction. Besides, the X-ray crystal data of a known compound dracoflavan B1 (9) was firstly reported. Daemoflavan G (7) represents a rare example of C-5 methylated 2-arylbenzofuran in natural products. Among the known compounds, 15, 16, 17 were reported from this species for the first time. All the compounds were evaluated for their cytotoxicity against HepG2 cell line. Among them, compounds 1, 9 and 10 exhibited modest cytotoxic activity with IC50 values of 12.4, 12.0 and 13.2 µM, respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Dracaena/química , Flavonoides/química , Frutas/química , Antineoplásicos Fitogênicos/isolamento & purificação , Células Hep G2 , Humanos , Indonésia , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
16.
Front Cell Neurosci ; 13: 130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031594

RESUMO

The deficits of cognitive flexibility (including attentional set-shifting and reversal learning) concomitant with dysfunction of the striatum are observed in several neuropsychiatric disorders. Rodent and human studies have identified the striatum [particularly the dorsomedial striatum (DMS) and nucleus accumbens (NAc)] as the critical locus for control of cognitive flexibility, but the effective neuromodulator and pharmacological control of cognitive flexibility remains to be determined. The adenosine A2A receptors (A2ARs) are highly enriched in the striatopallidal neurons where they integrate dopamine and glutamate signals to modulate several cognitive behaviors, but their contribution to cognitive flexibility control is unclear. In this study, by coupling an automated operant cognitive flexibility task with striatal subregional knockdown (KD) of the A2AR via the Cre-loxP strategy, we demonstrated that NAc A2AR KD improved cognitive flexibility with enhanced attentional set-shifting and reversal learning by decreasing regressive and perseverative errors, respectively. This facilitation was not attributed to mnemonic process or motor activity as NAc A2AR KD did not affect the visual discrimination, lever-pressing acquisition, and locomotor activity, but was associated with increased attention and motivation as evident by the progressive ratio test (PRT). In contrast to NAc A2ARs, DMS A2ARs KD neither affected visual discrimination nor improved set-shifting nor reversal learning, but promoted the effort-related motivation. Thus, NAc and DMS A2ARs exert dissociable controls of cognitive flexibility with NAc A2ARs KD selectively enhancing cognitive flexibility by facilitating strategy shifting with increased motivation/attention.

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