Cytoprotective Effect of Gallic Acid against Injuries Promoted by Therapeutic Ionizing Radiation in Preosteoblast Cells.

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Neuropathological Lesions and Cognitive Abilities in Black and White Older Adults in Brazil.

Importance: Race differences in dementia prevalence and incidence have previously been reported, with higher dementia burden in Black decedents. However, previous neuropathological studies were conducted mostly in convenience samples with White participants; conducting clinicopathological studies across populations is crucial for understanding the underlying dementia causes in individuals from different racial backgrounds. Objective: To compare the frequencies of neuropathological lesions and cognitive abilities between Black and White Brazilian adults in an autopsy study. Design, Setting, and Participants: This cross-sectional study used samples from the Biobank for Aging Studies, a population-based autopsy study conducted in Sao Paulo, Brazil. Participants were older adults whose family members consented to the brain donations; Asian participants and those with missing data were excluded. Samples were collected from 2004 to 2023. Neuropathologists were masked to cognitive outcomes. Exposure: Race as reported by the deceased's family member. Main Outcomes and Measures: The frequencies of neurodegenerative and cerebrovascular lesions were evaluated in 13 selected cerebral areas. Cognitive and functional abilities were examined with the Clinical Dementia Rating Scale. Results: The mean (SD) age of the 1815 participants was 74.0 (12.5) years, 903 (50%) were women, 617 (34%) were Black, and 637 (35%) had cognitive impairment. Small vessel disease (SVD) and siderocalcinosis were more frequent in Black compared with White participants (SVD: odds ratio [OR], 1.74; 95% CI, 1.29-2.35; P < .001; siderocalcinosis: OR, 1.70; 95% CI, 1.23-2.34; P = .001), while neuritic plaques were more frequent in White compared with Black participants (OR, 0.61; 95% CI, 0.44-0.83; P = .002). Likewise, Alzheimer disease neuropathological diagnosis was more frequent in White participants than Black participants (198 [39%] vs 77 [33%]), while vascular dementia was more common among Black participants than White participants (76 [32%] vs 121 [24%]). Race was not associated with cognitive abilities, nor did it modify the association between neuropathology and cognition. Conclusions and Relevance: In this cross-sectional study of Brazilian older adults, Alzheimer disease pathology was more frequent in White participants while vascular pathology was more frequent in Black participants. Further neuropathological studies in diverse samples are needed to understand race disparities in dementia burden.

Mat Pilates para tratamento da síncope vasovagal por telemedicina / Mat Pilates for treating vasovagal syncope via telemedicine

INTRODUÇÃO: A diminuição do retorno venoso é o mecanismo pivotal para o desencadeamento do reflexo vasovagal em pacientes com síncope reflexa. Programas de condicionamento físico (PCF) têm se mostrado promissores para diminuição da recorrência de eventos, possivelmente, pela melhoria do retorno venoso. Entretanto, PCF são caros e pouco acessíveis. O uso do mat Pilates por telemedicina (MPT) pode facilitar a disponibilidade desse tratamento. OBJETIVOS: Avaliar a recorrência de síncope/pré-síncope em pacientes com síncope vasovagal (SVV) submetidos a MPT; avaliar a segurança do MPT no tratamento da SVV. METODOLOGIA: Foram incluídos pacientes de 18 a 65 anos, com diagnóstico de SVV e pelo menos 1 episódio de síncope ou 2 de pré-síncope nos últimos 3 meses, do ambulatório de síncope da Universidade Federal de São Paulo e da seção de eletrofisiologia e arritmias do Instituto Dante Pazzanese de Cardiologia, entre março de 2022 e julho de 2023. Foram excluídos pacientes com evidência de doença cardíaca estrutural, doenças crônicas e com impossibilidade de horário. O MPT possuiu 36 sessões síncronas. Foram realizadas 3 sessões semanais, em grupos de até 3 pessoas, com 1 hora de duração. As fichas clínicas com parâmetros hemodinâmicos, eventos adversos e bem-estar foram preenchidas a cada sessão. O diário de síncope foi preenchido durante 90 dias. A avaliação de qualidade de vida WHOQOL-bref foi aplicado no início e fim do estudo. Todos os pacientes assinaram o termo de consentimento livre e esclarecido (CEP: 5.731.062). Foi considerado nível de significância <5%. RESULTADOS: Foram selecionados 229 pacientes, sendo excluídos 27% por doença cardíaca estrutural ou doenças crônicas, 55% por idade, 13% por indisponibilidade, dos quais 11 foram elegíveis e 9 concluíram o estudo. A redução na recorrência de síncope/pré-síncope foi observada após 45 dias de MPT quando comparado com o primeiro período (5,78±2,54 versus 4,00±3,57, p=0,035), gráfico 1. O WHOQOL-bref não apresentou diferença significativa. A assiduidade foi de 86%. Nenhum evento adverso foi observado durante o protocolo. CONCLUSÃO: O MPT reduziu o número de recorrências de SVV. O uso do MPT foi seguro para o tratamento dos pacientes na amostra estudada

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Mat pilates para tratamento da síncope vasovagal por telemedicina / Pilates mat for treating vasovagal syncope via telemedicine

INTRODUÇÃO: A diminuição do retorno venoso é o mecanismo pivotal para o desencadeamento do reflexo vasovagal em pacientes com síncope reflexa. Programas de condicionamento físico (PCF) têm se mostrado promissores para diminuição da recorrência de eventos, possivelmente, pela melhoria do retorno venoso. Entretanto, PCF são caros e pouco acessíveis. O uso do mat Pilates por telemedicina (MPT) pode facilitar a disponibilidade desse tratamento. OBJETIVOS: Avaliar a recorrência de síncope/ pré-síncope em pacientes com síncope vasovagal (SVV) submetidos a MPT; avaliar a segurança do MPT no tratamento da SVV. METODOLOGIA: Foram inclusos pacientes de 18 a 65 anos, com diagnóstico de SVV e pelo menos 1 episódio de síncope ou 2 de pré-síncope nos últimos 3 meses, do ambulatório de síncope da UNIFESP e da seção de eletrofisiologia e arritmias do IDPC, entre março de 2022 e julho de 2023. Foram excluídos pacientes com evidência de doença cardíaca estrutural (DCE), doenças crônicas (DCR) e com impossibilidade de horário. O MPT possuiu 36 sessões síncronas. Foram realizadas 3 sessões semanais, em grupos de até 3 pessoas, com 1 hora de duração. As fichas clínicas com parâmetros hemodinâmicos, eventos adversos e bemestar foram preenchidas a cada sessão. O diário de síncope foi preenchido durante 90 dias. O questionário WHOQOL foi aplicado no início e fim do estudo. Todos os pacientes assinaram o TCLE (CEP: 5.731.062). Foi considerado nível de significância <5%. RESULTADOS: Foram selecionados 229 pacientes, sendo excluídos 27% por DCR ou DCE, 55% por idade, 13% por indisponibilidade, dos quais 11 foram elegíveis e 9 concluíram o estudo. A redução na recorrência de síncope/pré-síncope foi observada após 45 dias de MPT quando comparado com o primeiro período (5,78±2,54 versus 4,00±3,57, p=0,035), gráfico 1. A média do bem-estar foi maior ao término de cada sessão quando comparado ao inicial, entretanto não modificou ao longo do MPT. O WHOQOL não apresentou diferença significativa. A assiduidade foi de 86%. Nenhum evento adverso foi observado durante o protocolo. CONCLUSÃO: O MPT reduziu o número de recorrências de SVV. O uso do MPT foi seguro para o tratamento dos pacientes na amostra estudada.

Synaptic proteasome is inhibited in Alzheimer's disease models and associates with memory impairment in mice.

The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models. We found a marked increase in ubiquitinylated proteins in post-mortem AD hippocampi compared to controls. Using several experimental models, we show that amyloid-ß oligomers (AßOs) inhibit synaptic proteasome activity and trigger a reduction in synaptic proteasome content. We further show proteasome inhibition specifically in hippocampal synaptic fractions derived from APPswePS1ΔE9 mice. Reduced synaptic proteasome activity instigated by AßOs is corrected by treatment with rolipram, a phosphodiesterase-4 inhibitor, in mice. Results further show that dynein inhibition blocks AßO-induced reduction in dendritic proteasome content in hippocampal neurons. Finally, proteasome inhibition induces AD-like pathological features, including reactive oxygen species and dendritic spine loss in hippocampal neurons, inhibition of hippocampal mRNA translation, and memory impairment in mice. Results suggest that proteasome inhibition may contribute to synaptic and memory deficits in AD.

Ecotoxicology applied to conservation: Potential negative metal and metalloid contamination effects on the homeostatic balance of the critically endangered Brazilian guitarfish, Pseudobatos horkelii (Elasmobranchii: Rhinobatidae).

Metal contamination poses a significant threat to elasmobranchs, underscoring the need for targeted conservation approaches. The critically endangered Brazilian guitarfish, Pseudobatos horkelii, confronts an array of challenges, notably overexploitation, putting its survival at risk. Our study investigated the potential toxicity arising from arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) contamination across various adult guitarfish tissues from southeastern Brazil. Serological stress indicators, nutritional metabolites, and creatinine, an organ function marker, were also assessed, and Selenium (Se) levels were also investigated for possible protective effects. Our investigation unveiled significant correlations between metal concentrations and the determined physiological markers, shedding light on potential adverse effects. Remarkably, six correlations were indicative of how Hg and Pb negatively impact hepatic metabolite assimilation, while As was shown to influence renal phosphorus dynamics, Cd to affect rectal gland phosphorus regulation, and Pb to influence creatinine production in muscle tissue. Furthermore, Se demonstrated protective properties against Cd, Hg, and Pb, suggesting a role in alleviating the toxicity of these elements. Despite probable protective Se influences, the detected elemental interactions still suggest potential for organ impairment. These findings gain heightened significance within the context of the cumulative stressors faced by the Brazilian guitarfish, with metal contamination exhibiting the capacity to erode this species resilience against both anthropogenic and environmental pressures, thereby disrupting systemic equilibrium and jeopardizing wild populations. By investigating the intricate balance between metal accumulation and physiological consequences, our study contributes with crucial insights into potential conservation strategy formulations towards pollution for this critically endangered elasmobranch species.

Perceptions of academics and nursing staff about the extension project: "Walking through the hospital".

OBJECTIVE: To know the perception of academics and nursing staff about the extension project "Walking through the hospital". METHOD: Qualitative study conducted in a Brazilian university hospital from November/2019 to April/2022 with nursing students and professionals participating in a university extension project. Data were collected using instruments on the Google Forms® platform and submitted to Content Thematic Analysis. The project was approved by the Ethics Committee. RESULTS: Fifteen academics, four nurses and six nursing technicians participated in the study. Four categories emerged from the analysis: "Knowing the hospital environment/dynamics", "Articulation between theory and practice","Bond between academics and health care professionals" and "Work process in the unit". FINAL CONSIDERATIONS: The findings highlight the importance of university extension in providing knowledge and experienceof hospital clinical practice, which can contribute to strengthening teaching and academic training in nursing.

Smoking Intensity Increases Diaphragm Muscle Injury: A Clinicopathologic Study.

BACKGROUND: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. METHODS: Subjects were divided into three groups: never-smoker (n = 46); less than 30 pack-years of smoking (n = 12); and more than 30 pack-years of smoking (n = 30). Diaphragm samples were stained with Picrosirius red and hematoxylin and eosin stain for general structure. RESULTS: Participants with more than 30 pack-years of cigarette smoking had a significant increase in adipocytes, blood vessels and collagen deposit, as well as an increase in histopathological alterations. CONCLUSIONS: Pack-years of smoking was associated with DIAm injury. However, further clinicopathological studies are needed to confirm our findings.

Smoking intensity increases diaphragm muscle injury: a clinicopathologic study

BACKGROUND: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. METHODS: Subjects were divided into three groups: never-smoker (n = 46); less than 30 pack-years of smoking (n = 12); and more than 30 pack-years of smoking (n = 30). Diaphragm samples were stained with Picrosirius red and hematoxylin and eosin stain for general structure. RESULTS: Participants with more than 30 pack-years of cigarette smoking had a significant increase in adipocytes, blood vessels and collagen deposit, as well as an increase in histopathological alterations. CONCLUSIONS: Pack-years of smoking was associated with DIAm injury. However, further clinicopathological studies are needed to confirm our findings.

The Potential Role of Selection Bias in the Association Between Coronary Atherosclerosis and Cognitive Impairment.

BACKGROUND: Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. OBJECTIVE: Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias in an autopsy study. METHODS: Coronary arteries were collected, and the largest luminal stenosis was measured. Sociodemographic, clinical, and cognitive information were reported by a reliable next-of-kin. The association was tested using logistic and linear regressions adjusted for sociodemographic and clinical variables. We restricted the sample to individuals that were born in 1935 or earlier and stratified the analysis by cause of death to investigate the role of selection bias. RESULTS: In 253 participants (mean age = 78.0±8.5 years old, 48% male), stenosis was not associated with cognitive impairment (OR = 0.85, 95% CI = 0.69; 1.06, p = 0.15). In individuals who were born before 1936 in the absence of cardiovascular disease as the cause of death, greater stenosis was associated with cognitive impairment (OR = 4.02, 95% CI = 1.39; 11.6, p = 0.01). On the other hand, this association was not present among those born in 1935 or earlier who died of cardiovascular diseases (OR = 0.83, 95% CI = 0.60; 1.16, p = 0.28). CONCLUSION: We found that higher coronary stenosis was associated with cognitive impairment only in individuals born in 1935 or earlier and who had not died from cardiovascular diseases. Selection bias may be an important issue when investigating risk factors for chronic degenerative diseases in older individuals using autopsy samples.

Alzheimer's disease brain-derived extracellular vesicles reveal altered synapse-related proteome and induce cognitive impairment in mice.

INTRODUCTION: Extracellular vesicles (EVs) have been implicated in the spread of neuropathology in Alzheimer's disease (AD), but their involvement in behavioral outcomes linked to AD remains to be determined. METHODS: EVs isolated from post mortem brain tissue from control, AD, or frontotemporal dementia (FTD) donors, as well as from APP/PS1 mice, were injected into the hippocampi of wild-type (WT) or a humanized Tau mouse model (hTau/mTauKO). Memory tests were carried out. Differentially expressed proteins in EVs were assessed by proteomics. RESULTS: Both AD-EVs and APP/PS1-EVs trigger memory impairment in WT mice. We further demonstrate that AD-EVs and FTD-EVs carry Tau protein, present altered protein composition associated with synapse regulation and transmission, and trigger memory impairment in hTau/mTauKO mice. DISCUSSION: Results demonstrate that AD-EVs and FTD-EVs have negative impacts on memory in mice and suggest that, in addition to spreading pathology, EVs may contribute to memory impairment in AD and FTD. HIGHLIGHTS: Aß was detected in EVs from post mortem AD brain tissue and APP/PS1 mice. Tau was enriched in EVs from post mortem AD, PSP and FTD brain tissue. AD-derived EVs and APP/PS1-EVs induce cognitive impairment in wild-type (WT) mice. AD- and FTD-derived EVs induce cognitive impairment in humanized Tau mice. Proteomics findings associate EVs with synapse dysregulation in tauopathies.

Impacto da pandemia da COVID-19 no estado funcional dos idosos: revisão de escopo / Impact of the COVID-19 pandemic on functional status in the elderly: scoping review.

Introdução: O processo de envelhecimento vem acompanhado de mudanças fisiológicas e estruturais, o isolamento social apresenta impacto negativo na vida dos longevos. Objetivo: Mapear as evidências sobre o impacto da pandemia da COVID-19 no estado funcional dos idosos. Métodos: Trata-se de uma revisão de escopo, cuja pesquisa foi realizada até dia 27 de janeiro de 2022, em cinco bases de dados. Foram incluídos 22 estudos nesta revisão, majoritariamente, os artigos foram desenvolvidos na Espanha, Itália, Israel e Polônia. Quanto aos periódicos eram especializados em saúde do idoso, como também saúde pública, medicina geral e nutrição. Os estudos eram do tipo coorte, ensaio clínico randomizados, observações clínicas, exploratório, retrospectivos e prospectivos. Participaram desses estudos 8741 pessoas. Resultados: Esta revisão permitiu mapear os principais impactos da pandemia COVID-19 sobre o estado funcional dos idosos, ficou evidente nos estudos a vulnerabilidade dessa população à doença, foi identificado que a idade é um fator de risco para aumento da mortalidade e os idosos que apresentavam o estado funcional preservado pré-COVID-19 tiveram um melhor desfecho em relação à recuperação hospitalar como também pós-COVID.

The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex.

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.

Age-Associated Upregulation of Glutamate Transporters and Glutamine Synthetase in Senescent Astrocytes In Vitro and in the Mouse and Human Hippocampus.

Aging is marked by complex and progressive physiological changes, including in the glutamatergic system, that lead to a decline of brain function. Increased content of senescent cells in the brain, such as glial cells, has been reported to impact cognition both in animal models and human tissue during normal aging and in the context of neurodegenerative disease. Changes in the glutamatergic synaptic activity rely on the glutamate-glutamine cycle, in which astrocytes handle glutamate taken up from synapses and provide glutamine for neurons, thus maintaining excitatory neurotransmission. However, the mechanisms of glutamate homeostasis in brain aging are still poorly understood. Herein, we showed that mouse senescent astrocytes in vitro undergo upregulation of GLT-1, GLAST, and glutamine synthetase (GS), along with the increased enzymatic activity of GS and [3H]-D-aspartate uptake. Furthermore, we observed higher levels of GS and increased [3H]-D-aspartate uptake in the hippocampus of aged mice, although the activity of GS was similar between young and old mice. Analysis of a previously available RNAseq dataset of mice at different ages revealed upregulation of GLAST and GS mRNA levels in hippocampal astrocytes during aging. Corroborating these rodent data, we showed an increased number of GS + cells, and GS and GLT-1 levels/intensity in the hippocampus of elderly humans. Our data suggest that aged astrocytes undergo molecular and functional changes that control glutamate-glutamine homeostasis upon brain aging.

Resilience of Neural Cellularity to the Influence of Low Educational Level.

BACKGROUND: Education is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also known to undergo neurogenesis in adulthood. We aimed to investigate the influence of education on the absolute cell numbers of the MTL (comprised by the hippocampal formation, amygdala, and parahippocampal gyrus) of men without cognitive impairment. METHODS: The Isotropic Fractionator technique was used to allow the anisotropic brain tissue to be transformed into an isotropic suspension of nuclei, and therefore assess the absolute cell composition of the MTL. We dissected twenty-six brains from men aged 47 to 64 years, with either low or high education. RESULTS: A significant difference between groups was observed in brain mass, but not in MTL mass. No significant difference was found between groups in the number of total cells, number of neurons, and number of non-neuronal cells. Regression analysis showed that the total number of cells, number of neurons, and number of non-neuronal cells in MTL were not affected by education. CONCLUSIONS: The results indicate a resilience of the absolute cellular composition of the MTL of typical men to low schooling, suggesting that the cellularity of brain regions is not affected by formal education.

Hyperphosphorylated Tau in Mesial Temporal Lobe Epilepsy: a Neuropathological and Cognitive Study.

Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal formation extracted from patients with drug-resistant mesial TLE undergoing surgery and postmortem non-sclerotic hippocampal formation of clinically and neuropathologically controls underwent immunohistochemistry against amyloid ß (Aß), hyperphosphorylated tau (p-tau), and TAR DNA-binding protein-43 (TDP-43) proteins, followed by quantitative analysis. Patients underwent a comprehensive neuropsychological evaluation prior to surgery. TLE hippocampi showed a significantly higher burden of p-tau than controls, whereas Aß deposits and abnormal inclusions of TDP-43 were absent in both groups. Patients with hippocampal sclerosis (HS) type 2 had higher immunostaining for p-tau than patients with HS type 1. In addition, p-tau burden was associated with impairment in attention tasks and seizures frequency. In this series of adults younger than 60 years-old, the increase of p-tau burden associated with higher frequency of seizures and attention impairment suggests the involvement of tau pathology as a potential contributor to cognitive deficits in mesial TLE.