What are the main oral manifestations in heart transplant patients? A scoping review.

OBJECTIVE: The purpose of this scoping review is to evaluate the oral manifestations (OM) of heart transplant (HT) patients undergoing immunosuppressive therapy (IT). MATERIAL AND METHODS: A literature search was performed using keywords and MeSH terms related to OM and HT in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until June 2023. Studies that evaluated HT individuals who used any IT and who reported the occurrence of OM were considered eligible. The results from the search were imported to EndNote Web, and duplicates were removed followed by title/abstract and full-text analysis. RESULTS: A total of 402 nonduplicated studies were found and 13 fulfilled the criteria and were included in the present review: 10 cross-sectional, 2 cohorts, and 1 clinical trial. The most reported OM were periodontal diseases, including drug-induced gingival enlargement (DIGE), gingival bleeding, gingivitis, and periodontitis. Reported in a minority of studies are oral cancer, opportunistic infections (oral hairy leukoplakia and erythematous candidiasis), enamel defects, and burning mouth. CONCLUSION: Considering the methodological heterogeneity of the studies analyzed, DIGE is the most commonly observed oral manifestation in HT individuals.

Mapping the lipidome in mitochondria-associated membranes (MAMs) in an in vitro model of Alzheimer's disease.

The disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the different subcellular fractions and analyzed by HILIC-LC-MS/MS and GC-MS, respectively. In this in vitro AD model, we observed a down-regulation in relative abundance of some phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) species with PUFA and few PC with saturated and long-chain FA. We also found an up-regulation of CL, and antioxidant alkyl acyl PL. Moreover, multivariate analysis indicated that each organelle has a specific lipid profile adaptation in N2A APPswe cells. In the FAs profile, we found an up-regulation of C16:0 in all subcellular fractions, a decrease of C18:0 levels in total fraction (TF) and microsomes fraction, and a down-regulation of 9-C18:1 was also found in mitochondria fraction in the AD model. Together, these results suggest that the over-expression of the familial APP Swedish mutation affects lipid homeostasis in MAMs and other subcellular fractions and supports the important role of lipids in AD physiopathology.

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site.

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.

Effect of Ferulago lutea (Poir.) Grande Essential Oil on Molecular Hallmarks of Skin Aging.

With the increase in global life expectancy, maintaining health into old age becomes a challenge, and research has thus concentrated on various strategies which aimed to mitigate the effects of skin aging. Aromatic plants stand out as promising sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EOs). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1ß protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence-associated ß-galactosidase, p21/p53 protein levels and the nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.

The journey of cardosin A in young Arabidopsis seedlings leads to evidence of a Golgi-independent pathway to the protein storage vacuole.

The aspartic proteinase cardosin A is a vacuolar enzyme found to accumulate in protein storage and lytic vacuoles in the flowers and protein bodies in the seeds of the native plant cardoon. Cardosin A was first isolated several decades ago and has since been extensively characterized, both in terms of tissue distribution and enzyme biochemistry. In the native system, several roles have been attributed to cardosin A, such as reproduction, reserve mobilization, and membrane remodeling. To participate in such diverse events, cardosin A must accumulate and travel to different compartments within the cell: protein storage vacuoles, lytic vacuoles, and the cytoplasmic membrane (and eventually outside the cell). Several studies have approached the expression of cardosin A in Arabidopsis thaliana and Nicotiana tabacum with promising results for the use of these systems to study of cardosin A trafficking. A poly-sorting mechanism has been uncovered for this protein, as two different vacuolar sorting determinants, mediating different vacuolar routes, have been described. The first is a conventional C-terminal domain, which delivers the protein to the vacuole via the Golgi, and the second is a more unconventional signal-the plant-specific insert (PSI)-that mediates a Golgi-independent route. The hypothesis that these two signals are activated according to cell needs and in organs with high metabolic activity is investigated here. An Arabidopsis line expressing cardosin A under an inducible promoter was used to understand the dynamics of cardosin A regarding vacuolar accumulation during seed germination events. Using antibodies against different regions of the protein and combining them with immunofluorescence and immunocytochemistry assays in different young seedling tissues, cardosin A was detected along the secretory pathway to the protein storage vacuole, often associated with the endoplasmic reticulum. More interestingly, upon treatment with the drug Brefeldin A, cardosin A was still detected in protein storage vacuoles, indicating that the intact protein can bypass the Golgi in this system, contrary to what was observed in N. tabacum. This study is a good starting point for further research involving the use of fluorescent fusions and exploring in more detail the relationship between cardosin A trafficking and plant development.

CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma.

Glioblastoma (GBM) is the most common and fatal primary tumor of the central nervous system (CNS) and current treatments have limited success. Chemokine signaling regulates both malignant cells and stromal cells of the tumor microenvironment (TME), constituting a potential therapeutic target against brain cancers. Here, we investigated the C-C chemokine receptor type 7 (CCR7) and the chemokine (C-C-motif) ligand 21 (CCL21) for their expression and function in human GBM and then assessed their therapeutic potential in preclinical mouse GBM models. In GBM patients, CCR7 expression positively associated with a poor survival. CCL21-CCR7 signaling was shown to regulate tumor cell migration and proliferation while also controlling tumor associated microglia/macrophage recruitment and VEGF-A production, thereby controlling vascular dysmorphia. Inhibition of CCL21-CCR7 signaling led to an increased sensitivity to temozolomide-induced tumor cell death. Collectively, our data indicate that drug targeting of CCL21-CCR7 signaling in tumor and TME cells is a therapeutic option against GBM.

Metabolic Disruption of Gold Nanospheres, Nanostars and Nanorods in Human Metastatic Prostate Cancer Cells.

Nanomaterials offer a broad spectrum of applications in biomedicine. The shapes of gold nanoparticles could modulate tumor cell behavior. Spherical (AuNPsp), stars (AuNPst) and rods (AuNPr) shapes of polyethylene glycol coated-gold nanoparticles (AuNPs-PEG) were synthesized. Metabolic activity, cellular proliferation, and reactive oxygen species (ROS) were measured and the impact of AuNPs-PEG in metabolic enzymes function was evaluated by RT-qPCR in PC3, DU145, and LNCaP prostate cancer cells. All AuNPs were internalized, and the different morphologies of AuNPs showed to be an essential modulator of metabolic activity. For PC3 and DU145, the metabolic activity of AuNPs was found to rank in the following order from lowest to highest: AuNPsp-PEG, AuNPst-PEG, and AuNPr-PEG. Regarding LNCaP cells, the AuNPst-PEG were less toxic, followed by AuNPsp-PEG and AuNPr-PEG, but it seems not to be dose-dependent. The proliferation was lower in AuNPr-PEG in PC3 and DU145 cells but was stimulated around 10% in most conditions (0.001-0.1 mM) in LNCaP cells (not statistically significant). For 1 mM, LNCaP cells showed a significant decrease in proliferation only for AuNPr-PEG. The outcomes of the current study demonstrated that different AuNPs conformations influence cell behavior, and the correct size and shape must be chosen considering its final application in the field of nanomedicine.

Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-ß (Aß) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.

Out-of-pocket expenditures associated with congenital zika syndrome in Brazil: an analysis of household health spending / Gastos out-of-pocket associados à síndrome congênita do vírus Zika no Brasil: uma análise dos gastos domiciliares em saúde

Objective: The study aims to estimate catastrophic health expenditures associated with the diagnosis and follow-up treatment of Congenital Zika Syndrome (CZS) in children affected during the 2015-2016 epidemic in Brazil. Catastrophic health expenditures are defined as health spending that exceeds a predefined proportion of the household's total expenditures, exposing family members to financial vulnerability. Methods: Ninety-six interviews were held in the cities of Fortaleza and Rio de Janeiro in a convenience sample, using a questionnaire on sociodemographic characteristics and private household expenditures associated with the syndrome, which also allowed estimating catastrophic expenditures resulting from care for CZS. Results: Most of the mothers interviewed in the study were brown, under 34 years of age, unemployed, and reported a monthly family income of two minimum wages or less. Spending on medicines accounted for 77.6% of the medical expenditures, while transportation and food were the main components of nonmedical expenditures, accounting for 79% of this total. The affected households were largely low-income and suffered catastrophic expenditures due to the disease. Considering the family income metric, in 41.7% of the households, expenses with the child's disease exceeded 10% of the household income. Conclusion: Public policies should consider the financial and healthcare needs of these families to ensure adequate support for individuals affected by CZS.

Objetivo: O estudo tem como objetivo estimar os gastos catastróficos em saúde associados ao diagnóstico e acompanhamento do tratamento da síndrome congênita do Zika (SCZ) em crianças afetadas durante a epidemia de 2015-2016 no Brasil. Gastos catastróficos em saúde são definidos como gastos com saúde que excedem uma proporção predefinida dos gastos totais do domicílio, expondo os membros da família à vulnerabilidade financeira. Métodos: Foram realizadas 96 entrevistas nas cidades de Fortaleza e Rio de Janeiro numa amostra de conveniência, por meio de questionário sobre características sociodemográficas e gastos privados domiciliares associados à síndrome, o que também permitiu estimar gastos catastróficos decorrentes do cuidado à SCZ. Resultados: A maioria das mães entrevistadas no estudo era parda, com menos de 34 anos, desempregada e com renda familiar mensal igual ou inferior a dois salários mínimos. Os gastos com medicamentos representaram 77,6% dos gastos médicos, enquanto transporte e alimentação foram os principais componentes dos gastos não médicos, respondendo por 79% desse total. Os domicílios afetados eram, em grande parte, de baixa renda e sofreram gastos catastróficos devido à doença. Considerando a métrica de renda familiar, em 41,7% dos domicílios, os gastos com a doença da criança ultrapassaram 10% da renda familiar. Conclusão: As políticas públicas devem considerar as necessidades financeiras e de saúde dessas famílias para garantir o suporte adequado aos indivíduos acometidos pela SCZ.

Action of Hyaluronic Acid as a Damage-Associated Molecular Pattern Molecule and Its Function on the Treatment of Temporomandibular Disorders.

The temporomandibular joint is responsible for fundamental functions. However, mechanical overload or microtraumas can cause temporomandibular disorders (TMD). In addition to external factors, it is known that these conditions are involved in complex biological mechanisms, such as activation of the immune system, activation of the inflammatory process, and degradation of extracellular matrix (ECM) components. The ECM is a non-cellular three-dimensional macromolecular network; its most studied components is hyaluronic acid (HA). HA is naturally found in many tissues, and most of it has a high molecular weight. HA has attributed an essential role in the viscoelastic properties of the synovial fluid and other tissues. Additionally, it has been shown that HA molecules can contribute to other mechanisms in the processes of injury and healing. It has been speculated that the degradation product of high molecular weight HA in healthy tissues during injury, a low molecular weight HA, may act as damage-associated molecular patterns (DAMPs). DAMPs are multifunctional and structurally diverse molecules that play critical intracellular roles in the absence of injury or infection. However, after cellular damage or stress, these molecules promote the activation of the immune response. Fragments from the degradation of HA can also act as immune response activators. Low molecular weight HA would have the ability to act as a pro-inflammatory marker, promoting the activation and maturation of dendritic cells, the release of pro-inflammatory cytokines such as interleukin 1 beta (IL-1ß), and tumor necrosis factor α (TNF-α). It also increases the expression of chemokines and cell proliferation. Many of the pro-inflammatory effects of low molecular weight HA are attributed to its interactions with the activation of toll-like receptors (TLRs 2 and 4). In contrast, the high molecular weight HA found in healthy tissues would act as an anti-inflammatory, inhibiting cell growth and differentiation, decreasing the production of inflammatory cytokines, and reducing phagocytosis by macrophages. These anti-inflammatory effects are mainly attributed to the interaction of high-weight HA with the CD44 receptor. In this study, we review the action of the HA as a DAMP and its functions on pain control, more specifically in orofacial origin (e.g., TMD).

O financiamento da infraestrutura urbana de esporte no Brasil: fontes, magnitude e direcionamento do orçamento federal de 2004 a 2019 / Financing urban sports infrastructure in Brazil: sources, magnitude and direction of the federal budget from 2004 to 2019

O objetivo desta investigação científica foi analisar o financiamento e gasto do orçamento público federal com a infraestrutura urbana de esporte de 2004 a 2019. O estudo se caracteriza como uma pesquisa descritivo-exploratória, de cunho quantiqualitativo, desenvolvida a partir de levantamento documental no Siga Brasil, tendo sido os dados analisados a partir dos indicadores "fontes de financiamento", "magnitude" e "direção do gasto". A maioria dos recursos para infraestrutura de esporte foi proveniente do Ministério do Esporte/Secretaria Especial do Esporte e de recursos ordinários advindos de emendas parlamentares. Ao longo do tempo oscilaram bastante os referidos gastos, tendo eles sofrido contingenciamentos. O direcionamento dos recursos se deu, principalmente, com grandes eventos esportivos e esteve concentrado na região Sudeste.

The objective of this scientific investigation was to analyze the financing and expenditure of the federal public budget on urban sports infrastructure from 2004 to 2019. The study is characterized as descriptive-exploratory research, with a quantitative and qualitative nature, developed from a survey document in Siga Brasil, the data having been analyzed based on indicators of funding sources, magnitude and direction of expenditure. Most of the resources for sports infrastructure came from the Ministério do Esporte/Secretaria Especial do Esporte and from ordinary resources arising from parliamentary amendments. Over time, these expenses fluctuated a lot, having suffered restrictions. The allocation of resources took place, mainly, with major sporting events and were concentrated in the Southeast region.

Outbreak of KPC-producing Klebsiella pneumoniae at a Portuguese university hospital: Epidemiological characterization and containment measures.

Background: KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal. Methods: A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records. Results: Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection. Conclusions: Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak.

Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis in children and adolescents

ABSTRACT This prospective study describes the use of Gene-Xpert Ultra for the diagnosis of extrapulmonary tuberculosis (EPTB) in children and adolescents, in Rio de Janeiro, Brazil. Eighteen patients were studied; the final diagnosis of EPTB was established in 13 (72%). Gene-Xpert Ultra results showed detection in 10/13 (77%) of EPTB cases (7 of these 10 with trace-positive results). Gene-Xpert Ultra proved to be a promising method for the diagnosis of childhood EPTB.

Efeito colateral da pandemia de Covid-19 no Brasil sobre o número de procedimentos diagnósticos e de tratamento da sífilis / Side effect of the COVID-19 pandemic in Brazil on the number of diagnostic and treatment procedures for syphilis / Efecto secundario de la pandemia de Covid-19 en Brasil sobre el número de procedimientos de diagnóstico y tratamiento de la sífilis

A sífilis, uma infecção vertical e sexualmente transmissível, curável e prevenível, é um problema de saúde pública no Brasil. Métodos diagnósticos e tratamentos são importantes no controle da doença. A pandemia de Covid-19 causou atrasos em diagnósticos e no tratamento na atenção primária em várias doenças e em diversos países, pois interrompeu padrões usuais de atendimento à saúde. O objetivo do estudo é identificar se houve menor número de procedimentos diagnósticos e de tratamento realizados para sífilis nos primeiros sete meses de 2020, comparativamente à média dos mesmos meses entre 2016 e 2019, no Brasil e nas unidades federativas. A redução no número de procedimentos seria um indicativo de atraso no diagnóstico, na detecção e no tratamento da sífilis em 2020. Foram utilizadas informações disponibilizadas no Sistema de Informações Ambulatoriais (SIA/SUS). Os achados para o Brasil indicaram queda de 1/3 nos procedimentos de diagnóstico e de tratamento referentes à sífilis nos sete primeiros meses do ano da pandemia, comparados com a média dos sete primeiros meses nos quatro anos anteriores (2016-2019). Indicadores mostram diferenças importantes por unidades da federação, apontando para maiores quedas proporcionais nos volumes de procedimentos no Norte e Nordeste, com ênfase nos estados do Maranhão, Roraima, Pará, Bahia, Rio Grande do Norte, Amazonas, Pernambuco e Amapá.

Syphilis, a vertical and sexually transmitted infection, curable and preventable, is a public health problem in Brazil. Diagnostic methods and treatments are important in controlling the disease. The COVID-19 pandemic caused delays in diagnosis and lack of treatment in primary care in several diseases and in several countries, as the pandemic disrupted usual health care standards. The aim of the study was to identify whether there were fewer diagnostic and treatment procedures performed for syphilis in the first seven months of 2020, compared to the average for the same months between 2016 and 2019, in Brazil and Federative Units. The reduction in the number of procedures would be indicative of a delay in the diagnosis, detection and treatment of syphilis in 2020. Information used came from the Outpatient Information System (SIA / SUS). The findings for Brazil indicated a 1/3 drop in diagnosis and treatment procedures for syphilis in the first seven months of the year of the COVID-19 pandemic, compared with the first seven months of the previous four years (2016-2019). Indicators showed important differences by Federation Units, pointing to greater proportional decrease in the volume of procedures in the North and Northeast, with an emphasis on Maranhão, Roraima, Pará, Bahia, Rio Grande do Norte, Amazonas, Pernambuco and Amapá.

La sífilis, una infección vertical y de transmisión sexual, curable y prevenible, es un problema de salud pública en Brasil. Los métodos de diagnóstico y los tratamientos son importantes para controlar la enfermedad. La pandemia de Covid-19 provocó retrasos en el diagnóstico y tratamiento en la atención primaria de variadas enfermedades en varios países, ya que interrumpió los estándares habituales de atención de la salud. El objetivo del estudio fue identificar si se realizaron menos procedimientos de diagnóstico y tratamiento de la sífilis en los primeros siete meses de 2020 en comparación con la media de los mismos meses entre 2016 y 2019, en Brasil y en sus unidades federativas. La reducción del número de procedimientos indicaría indicativo de un retraso en el diagnóstico, la detección temprana y el tratamiento de la sífilis en 2020. Para ello se utilizó la información disponible en el Sistema de Información Ambulatoria (SIA/SUS). Los hallazgos indicaron una caída de un tercio en los procedimientos de diagnóstico y tratamiento de la sífilis en los primeros siete meses del año de la pandemia de Covid-19 para Brasil, en comparación con los primeros siete meses de los cuatro años anteriores (2016-2019). Los indicadores mostraron diferencias importantes por unidades de la Federación, apuntando a mayores caídas proporcionales en el volumen de trámites en el Norte y Nordeste, con énfasis en Maranhão, Roraima, Pará, Bahia, Rio Grande do Norte, Amazonas, Pernambuco y Amapá.

Structural and Functional Alterations in Mitochondria-Associated Membranes (MAMs) and in Mitochondria Activate Stress Response Mechanisms in an In Vitro Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of extracellular plaques composed by amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. AD-related neurodegenerative mechanisms involve early changes of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and impairment of cellular events modulated by these subcellular domains. In this study, we characterized the structural and functional alterations at MAM, mitochondria, and ER/microsomes in a mouse neuroblastoma cell line (N2A) overexpressing the human amyloid precursor protein (APP) with the familial Swedish mutation (APPswe). Proteins levels were determined by Western blot, ER-mitochondria contacts were quantified by transmission electron microscopy, and Ca2+ homeostasis and mitochondria function were analyzed using fluorescent probes and Seahorse assays. In this in vitro AD model, we found APP accumulated in MAM and mitochondria, and altered levels of proteins implicated in ER-mitochondria tethering, Ca2+ signaling, mitochondrial dynamics, biogenesis and protein import, as well as in the stress response. Moreover, we observed a decreased number of close ER-mitochondria contacts, activation of the ER unfolded protein response, reduced Ca2+ transfer from ER to mitochondria, and impaired mitochondrial function. Together, these results demonstrate that several subcellular alterations occur in AD-like neuronal cells, which supports that the defective ER-mitochondria crosstalk is an important player in AD physiopathology.