Prevalence of Attempted Suicide by Exogenous Poisoning with Medication in the City of Salvador, Bahia, in the Period of 2015-2019 / Prevalência de Tentativa de Suicídio por Intoxicação Exógena com Medicamentos na Cidade de Salvador, Bahia, no Período de 2015-2019

Exogenous intoxication is one of the main mechanisms used in suicide attempts in Brazil, making it a condition of weekly, compulsory notification. The aim of this study is to analyze the prevalence of suicide attempts induced by medication in the city of Salvador, Bahia from 2015 to 2019. This is an ecological study following a time-trend analysis. People who used pharmacological drugs that led to exogenous intoxication for the purpose of committing suicide were included and cases in which the attempt was successful were excluded. The data search was made on DATASUS and SUVISA, and the following data were collected: race, sex, suicide attempt, detailed age, occupation, medication and city. 1418 victims of suicide attempts due to exogenous drug intoxication were reported in the years 2015 to 2019. Of this total, the prevalent demographic characteristics for victims of suicide attempt due to exogenous pharmacological intoxication were the female sex, brown race, age group from 20 to 34 years old, complete high school education, and students. With these findings, the present study aims to emphasize this condition of compulsory notification, since the reversal of these growing data requires the implementation of public policies and health programs that provide a greater awareness of the topic and access to trained professionals, in addition to the dissemination of information.(AU)

A intoxicação exógena é um dos principais mecanismos utilizados nas tentativas de suicídio no Brasil, tornando-se condição de notificação compulsória semanal. O objetivo deste estudo é analisar a prevalência de tentativas de suicídio induzidas por medicamentos na cidade de Salvador, Bahia, no período de 2015 a 2019. Trata-se de um estudo ecológico seguindo uma análise de tendência temporal. Foram incluídas pessoas que utilizaram medicamentos farmacológicos que levaram à intoxicação exógena com o objetivo de cometer suicídio e excluídos os casos em que a tentativa foi bem-sucedida. A busca de dados foi feita no DATASUS e SUVISA, e foram coletados os seguintes dados: raça, sexo, tentativa de suicídio, idade detalhada, ocupação, medicamento e cidade. Foram notificadas 1.418 vítimas de tentativas de suicídio por intoxicação medicamentosa exógena nos anos de 2015 a 2019. Desse total, as características demográficas prevalentes para vítimas de tentativa de suicídio por intoxicação farmacológica exógena foram o sexo feminino, a raça parda, a faixa etária de 20 a 34 anos, ensino médio completo, e estudantes. Com esses achados, o presente estudo visa enfatizar essa condição de notificação compulsória, uma vez que a reversão desses dados crescentes exige a implantação de políticas públicas e programas de saúde que proporcionem maior conscientização sobre o tema e acesso a profissionais capacitados, além do disseminação de informação. (AU)

Heads Up! Interlinked Amyloidogenic and Axonal Transport Pathways in Concussion-Induced Neurodegeneration.

Mild traumatic brain injury (mTBI), a condition in which brain function is transiently disrupted by a mechanical force, is a major risk factor for developing Alzheimer's disease (AD) and other neurodegenerative conditions. In this commentary, we summarize recent findings in human neurons derived from induced pluripotent stem cells, detailing early neuronal events following mild injury that may seed future neurodegeneration. In particular, we discuss interlinked relationships between mTBI and several biological pathways hypothesized to underlie AD progression, including amyloidogenic cleavage of amyloid precursor protein (APP), impairment of axonal transport, and the development of APP-associated axonal swellings. We also describe the implications of these findings for future mechanistic and translational studies.

Alkaline activation of endogenous latent TGFß1 by an injectable hydrogel directs cell homing for in situ complex tissue regeneration.

Utilization of the body's regenerative potential for tissue repair is known as in situ tissue regeneration. However, the use of exogenous growth factors requires delicate control of the dose and delivery strategies and may be accompanied by safety, efficacy and cost concerns. In this study, we developed, for the first time, a biomaterial-based strategy to activate endogenous transforming growth factor beta 1 (TGFß1) under alkaline conditions for effective in situ tissue regeneration. We demonstrated that alkaline-activated TGFß1 from blood serum, bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable of increasing cell recruitment and early differentiation, implying its broad practicability. Furthermore, we engineered an injectable hydrogel (MS-Gel) consisting of gelatin microspheres for loading strong alkaline substances and a modified gelatin matrix for hydrogel click crosslinking. In vitro models showed that alkaline MS-Gel controllably and sustainably activated endogenous TGFß1 from tooth dentin for robust bone marrow stem cell migration. More importantly, infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted significant pulp-dentin regeneration with neurovascular stroma and mineralized tissue by endogenous proliferative cells. Therefore, this work offers a new bench-to-beside translation strategy using biomaterial-activated endogenous biomolecules to achieve in situ tissue regeneration without the need for cell or protein delivery.

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons.

Traumatic brain injury (TBI) results in disrupted brain function following impact from an external force and is a risk factor for sporadic Alzheimer's disease (AD). Although neurologic symptoms triggered by mild traumatic brain injuries (mTBI), the most common form of TBI, typically resolve rapidly, even an isolated mTBI event can increase the risk to develop AD. Aberrant accumulation of amyloid ß peptide (Aß), a cleaved fragment of amyloid precursor protein (APP), is a key pathologic outcome designating the progression of AD following mTBI and has also been linked to impaired axonal transport. However, relationships among mTBI, amyloidogenesis, and axonal transport remain unclear, in part because of the dearth of human models to study the neuronal response following mTBI. Here, we implemented a custom-microfabricated device to deform neurons derived from human-induced pluripotent stem cells, derived from a cognitively unimpaired male individual, to mimic the mild stretch experienced by neurons during mTBI. Although no cell lethality or cytoskeletal disruptions were observed, mild stretch was sufficient to stimulate rapid amyloidogenic processing of APP. This processing led to abrupt cessation of APP axonal transport and progressive formation of aberrant axonal accumulations that contained APP, its processing machinery, and amyloidogenic fragments. Consistent with this sequence of events, stretch-induced defects were abrogated by reducing amyloidogenesis either pharmacologically or genetically. In sum, we have uncovered a novel and manipulable stretch-induced amyloidogenic pathway directly responsible for APP axonal transport dysregulation. Our findings may help to understand and ultimately mitigate the risk of developing AD following mTBI.SIGNIFICANCE STATEMENT Mild traumatic brain injury is a risk factor for sporadic Alzheimer's disease (AD). Increased amyloid ß peptide generation after injury may drive this risk. Here, by using a custom-built device to impose mild stretch to human neurons, we found that stretch triggers amyloid precursor protein (APP) cleavage, and thus amyloid ß peptide generation, consequently disrupting APP axonal transport. Compellingly, protecting APP from cleavage was sufficient to spare axonal transport dysregulation and the consequent aberrant axonal accumulation of APP. Supporting such protective mechanism, the expression of the AD-protective APPA673T genetic variant conferred protection against stretch-induced APP axonal transport phenotypes. Our data reveal potential subcellular pathways contributing to the development of AD-associated phenotypes following mild traumatic brain injury, and putative strategies for intervening in these pathways.

Paper-thin multilayer microfluidic devices with integrated valves.

Integrated valve microfluidics has an unparalleled capability to automate rapid delivery of fluids at the nanoliter scale for high-throughput biological experimentation. However, multilayer soft lithography, which is used to fabricate valve-microfluidics, produces devices with a minimum thickness of around five millimeters. This form-factor limitation prevents the use of such devices in experiments with limited sample thickness tolerance such as 4-pi microscopy, stimulated Raman scattering microscopy, and many forms of optical or magnetic tweezer applications. We present a new generation of integrated valve microfluidic devices that are less than 300 µm thick, including the cover-glass substrate, that resolves the thickness limitation. This "thin-chip" was fabricated through a novel soft-lithography technique that produces on-chip micro-valves with the same functionality and reliability of traditional thick valve-microfluidic devices despite the orders of magnitude reduction in thickness. We demonstrated the advantage of using our thin-chip over traditional thick devices to automate fluid control while imaging on a high-resolution inverted microscope. First, we demonstrate that the thin-chip provides an improved signal to noise when imaging single cells with two-color stimulated Raman scattering (SRS). We then demonstrated how the thin-chip can be used to simultaneously perform on-chip magnetic manipulation of beads and fluorescent imaging. This study reveals the potential of our thin-chip in high-resolution imaging, sorting, and bead capture-based single-cell multi-omics applications.

Cholesterol-lowering drugs reduce APP processing to Aß by inducing APP dimerization.

Amyloid beta (Aß) is a major component of amyloid plaques, which are a key pathological hallmark found in the brains of Alzheimer's disease (AD) patients. We show that statins are effective at reducing Aß in human neurons from nondemented control subjects, as well as subjects with familial AD and sporadic AD. Aß is derived from amyloid precursor protein (APP) through sequential proteolytic cleavage by BACE1 and γ-secretase. While previous studies have shown that cholesterol metabolism regulates APP processing to Aß, the mechanism is not well understood. We used iPSC-derived neurons and bimolecular fluorescence complementation assays in transfected cells to elucidate how altering cholesterol metabolism influences APP processing. Altering cholesterol metabolism using statins decreased the generation of sAPPß and increased levels of full-length APP (flAPP), indicative of reduced processing of APP by BACE1. We further show that statins decrease flAPP interaction with BACE1 and enhance APP dimerization. Additionally, statin-induced changes in APP dimerization and APP-BACE1 are dependent on cholesterol binding to APP. Our data indicate that statins reduce Aß production by decreasing BACE1 interaction with flAPP and suggest that this process may be regulated through competition between APP dimerization and APP cholesterol binding.

Hypotension and Bradycardia Produced by Transthoracic Application of Low-Intensity Ultrasound Therapy in Hearts of Healthy Rats - A Preclinical Study.

OBJECTIVE: To investigate the cardiovascular effects produced by transthoracic application of low-intensity pulsed ultrasound therapy (LIPUST). METHODS: Three-month-old male Wistar rats (± 300 g, N=16) were randomly allocated in two groups, namely SHAM (control group, faked procedures) and UST (animals treated with LIPUST). These animals, under anesthesia, were instrumented (femoral artery and vein catheterization) for hemodynamic recordings (mean blood pressure [MBP], heart rate [HR]) and blood biochemical profile (lipids, creatine kinase-myocardial band [CK-MB]). Then, LIPUST (spatial average-temporal average [ISATA] 1-MHz, power 0.1 to 1.2 W/cm2, pulsed 2:8 ms, cycle at 30%, for three minutes) was applied to animals from the UST group, externally to their thorax. SHAM animals were equally manipulated, but without application of ultrasound energy. After the hemodynamic and biochemical measurements, animals were sacrificed, and their hearts were mounted in a Langendorff apparatus for coronary reactivity evaluation. Standard histology techniques were employed to analyze the hearts. RESULTS: LIPUST application caused statistically significant reductions in MBP (92±4 vs. 106±1 mmHg) and HR (345±14 vs. 380±17 rpm) when compared with SHAM procedures. UST rats exhibited higher CK-MB levels (318±55 vs. 198±26 U/dL) and lower plasma triglycerides levels (38±7 vs. 70±10 mg/dL) than SHAM animals. Coronary reactivity was not significantly changed by LIPUST. Cardiac histopathology showed an increase in capillary permeability in treated animals when compared with SHAM animals. CONCLUSION: Noninvasive LIPUST induces significant metabolic and hemodynamic changes, including intensity-dependent bradycardia and hypotension, indicating a possible therapeutic effect for cardiac events.

Hypotension and bradycardia produced by transthoracic application of low-intensity ultrasound therapy in hearts of healthy rats - a preclinical study

Abstract Objective: To investigate the cardiovascular effects produced by transthoracic application of low-intensity pulsed ultrasound therapy (LIPUST). Methods: Three-month-old male Wistar rats (± 300 g, N=16) were randomly allocated in two groups, namely SHAM (control group, faked procedures) and UST (animals treated with LIPUST). These animals, under anesthesia, were instrumented (femoral artery and vein catheterization) for hemodynamic recordings (mean blood pressure [MBP], heart rate [HR]) and blood biochemical profile (lipids, creatine kinase-myocardial band [CK-MB]). Then, LIPUST (spatial average-temporal average [ISATA] 1-MHz, power 0.1 to 1.2 W/cm2, pulsed 2:8 ms, cycle at 30%, for three minutes) was applied to animals from the UST group, externally to their thorax. SHAM animals were equally manipulated, but without application of ultrasound energy. After the hemodynamic and biochemical measurements, animals were sacrificed, and their hearts were mounted in a Langendorff apparatus for coronary reactivity evaluation. Standard histology techniques were employed to analyze the hearts. Results: LIPUST application caused statistically significant reductions in MBP (92±4 vs. 106±1 mmHg) and HR (345±14 vs. 380±17 rpm) when compared with SHAM procedures. UST rats exhibited higher CK-MB levels (318±55 vs. 198±26 U/dL) and lower plasma triglycerides levels (38±7 vs. 70±10 mg/dL) than SHAM animals. Coronary reactivity was not significantly changed by LIPUST. Cardiac histopathology showed an increase in capillary permeability in treated animals when compared with SHAM animals. Conclusion: Noninvasive LIPUST induces significant metabolic and hemodynamic changes, including intensity-dependent bradycardia and hypotension, indicating a possible therapeutic effect for cardiac events.

Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells.

In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation.

A Multiplexed Serologic Test for Diagnosis of Lyme Disease for Point-of-Care Use.

Single multiplexed assays could replace the standard 2-tiered (STT) algorithm recommended for the laboratory diagnosis of Lyme disease if they perform with a specificity and a sensitivity superior or equal to those of the STT algorithm. We used human serum rigorously characterized to be sera from patients with acute- and convalescent-phase early Lyme disease, Lyme arthritis, and posttreatment Lyme disease syndrome, as well as the necessary controls (n = 241 samples), to select the best of 12 Borrelia burgdorferi proteins to improve our microfluidic assay (mChip-Ld). We then evaluated its serodiagnostic performance in comparison to that of a first-tier enzyme immunoassay and the STT algorithm. We observed that more antigens became positive as Lyme disease progressed from early to late stages. We selected three antigens (3Ag) to include in the mChip-Ld: VlsE and a proprietary synthetic 33-mer peptide (PepVF) to capture sensitivity in all disease stages and OspC for early Lyme disease. With the specificity set at 95%, the sensitivity of the mChip-Ld with 3Ag ranged from 80% (95% confidence interval [CI], 56% to 94%) and 85% (95% CI, 74% to 96%) for two panels of serum from patients with early Lyme disease and was 100% (95% CI, 83% to 100%) for serum from patients with Lyme arthritis; the STT algorithm detected early Lyme disease in the same two panels of serum from patients with early Lyme disease with a sensitivity of 48.5% and 75% and Lyme arthritis in serum from patients with Lyme arthritis with a sensitivity of 100%, and the specificity was 97.5% to 100%. The mChip-Ld platform outperformed the STT algorithm according to sensitivity. These results open the door for the development of a single, rapid, multiplexed diagnostic test for point-of-care use that can be designed to identify the Lyme disease stage.

Mild Exercise Differently Affects Proteostasis and Oxidative Stress on Motor Areas During Neurodegeneration: A Comparative Study of Three Treadmill Running Protocols.

Proteostasis and oxidative stress were evaluated in motor cortex and spinal cord of aged Lewis rats exposed to 1 mg/kg/day of rotenone during 4 or 8 weeks, prior or after practicing three protocols of mild treadmill running. Results demonstrated that exercise done after the beginning of neurodegeneration reverted the increased oxidative stress (measured by H2O2 levels and SOD activity), increased neuron strength, and improved proteostasis in motor cortex. Spinal cord was not affected. Treadmill running practiced before neurodegeneration protected cortical motor neurons of the rotenone-exposed rats; but in this case, oxidative stress was not altered, whereas proteasome activity was increased and autophagy decreased. Spinal cord was not protected when exercise was practiced before neurodegeneration. Prolonged treadmill running (10 weeks) increased oxidative stress, autophagy, and proteasome activity, whereas neuron viability was decreased in motor cortex. In spinal cord, this protocol decreased oxidative stress and increased proteasome activity. Major conclusions were that treadmill running practiced before or after the beginning of neurodegeneration may protect motor cortex neurons, whereas prolonged mild running seems to be beneficial for spinal cord.

Mild exercise differently affects proteostasis and oxidative stress on motor areas during neurodegeneration: a comparative study of three treadmill running protocols

Proteostasis and oxidative stress were evaluated in motor cortex and spinal cord of aged Lewis rats exposed to 1mg/kg/day of rotenone during 4 or 8weeks, prior or after practicing three protocols of mild treadmill running. Results demonstrated that exercise done after the beginning of neurodegeneration reverted the increased oxidative stress (measured by H2O2 levels and SOD activity), increased neuron strength, and improved proteostasis in motor cortex. Spinal cord was not affected. Treadmill running practiced before neurodegeneration protected cortical motor neurons of the rotenone-exposed rats; but in this case, oxidative stress was not altered, whereas proteasome activity was increased and autophagy decreased. Spinal cord was not protected when exercise was practiced before neurodegeneration. Prolonged treadmill running (10weeks) increased oxidative stress, autophagy, and proteasome activity, whereas neuron viability was decreased in motor cortex. In spinal cord, this protocol decreased oxidative stress and increased proteasome activity. Major conclusions were that treadmill running practiced before or after the beginning of neurodegeneration may protect motor cortex neurons, whereas prolonged mild running seems to be beneficial for spinal cord.

Mild exercise differently affects proteostasis and oxidative stress on motor areas during neurodegeneration: a comparative study of three treadmill running protocols

Proteostasis and oxidative stress were evaluated in motor cortex and spinal cord of aged Lewis rats exposed to 1mg/kg/day of rotenone during 4 or 8weeks, prior or after practicing three protocols of mild treadmill running. Results demonstrated that exercise done after the beginning of neurodegeneration reverted the increased oxidative stress (measured by H2O2 levels and SOD activity), increased neuron strength, and improved proteostasis in motor cortex. Spinal cord was not affected. Treadmill running practiced before neurodegeneration protected cortical motor neurons of the rotenone-exposed rats; but in this case, oxidative stress was not altered, whereas proteasome activity was increased and autophagy decreased. Spinal cord was not protected when exercise was practiced before neurodegeneration. Prolonged treadmill running (10weeks) increased oxidative stress, autophagy, and proteasome activity, whereas neuron viability was decreased in motor cortex. In spinal cord, this protocol decreased oxidative stress and increased proteasome activity. Major conclusions were that treadmill running practiced before or after the beginning of neurodegeneration may protect motor cortex neurons, whereas prolonged mild running seems to be beneficial for spinal cord.

Incontinencia urinaria de esfuerzo por deficiencia esfinteriana / Urinary incontinence of esfinterial deficiency effort

Resumen El objetivo de la presente revisión es esclarecer los conocimientos generales de la incontinencia urinaria por deficiencia esfinteriana, su diagnóstico y opciones terapéuticas. La metodología usada para la realización de este trabajo fue revisión de literatura exploratoria y descriptiva. La incontinencia urinaria tiene impacto en la calidad de vida de las mujeres en la menopausia, y actualmente se realizan diversas opciones terapéuticas deforma mínimamente invasiva por los nuevos avances tecnológicos. El diagnóstico de la IUE se basa en la realización de manera eficaz y ordenada de un examen ginecológico completo, incluyendo procedimientos técnicos. En el tratamiento, la cirugía de slings es la más usada actualmente, concomitante con las medidas-higiénico dietéticas y las técnicas psicológicas de modificación de conductas; los parámetros de calidad de vida más afectados son la actividad sexual, la urgencia miccional y las infecciones urinarias frecuentes.

Abstract The objective of this study is to clarify the general knowledge of urinary incontinence due to sphincter deficiency, its diagnosis and therapeutic options. the methodology used to carry out this work was a review of exploratory and descriptive literature. Urinary incontinence exerts an impact on the quality of life of women during menopause, and various therapeutic options are currently performed in a minimally invasive manner due to new technological advances. The diagnosis of SUI is based on the effective and orderly performance of a complete gynecological examination, including technical procedures. In the treatment, slings surgery is the most used currently, concomitant with the hygienic dietary measures and the psychological techniques of behavior modification; The most affected quality of life parameters are sexual activity, urgency and frequent urinary tract infections.

Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-ß clearance in human astrocytes.

Mounting evidence suggests that alterations in cholesterol homeostasis are involved in Alzheimer's disease (AD) pathogenesis. Amyloid precursor protein (APP) or multiple fragments generated by proteolytic processing of APP have previously been implicated in the regulation of cholesterol metabolism. However, the physiological function of APP in regulating lipoprotein homeostasis in astrocytes, which are responsible for de novo cholesterol biosynthesis and regulation in the brain, remains unclear. To address this, here we used CRISPR/Cas9 genome editing to generate isogenic APP-knockout (KO) human induced pluripotent stem cells (hiPSCs) and differentiated them into human astrocytes. We found that APP-KO astrocytes have reduced cholesterol and elevated levels of sterol regulatory element-binding protein (SREBP) target gene transcripts and proteins, which were both downstream consequences of reduced lipoprotein endocytosis. To elucidate which APP fragments regulate cholesterol homeostasis and to examine whether familial AD mutations in APP affect lipoprotein metabolism, we analyzed an isogenic allelic series harboring the APP Swedish and APP V717F variants. Only astrocytes homozygous for the APP Swedish (APPSwe/Swe) mutation, which had reduced full-length APP (FL APP) due to increased ß-secretase cleavage, recapitulated the APP-KO phenotypes. Astrocytic internalization of ß-amyloid (Aß), another ligand for low-density lipoprotein (LDL) receptors, was also impaired in APP-KO and APPSwe/Swe astrocytes. Finally, impairing cleavage of FL APP through ß-secretase inhibition in APPSwe/Swe astrocytes reversed the LDL and Aß endocytosis defects. In conclusion, FL APP is involved in the endocytosis of LDL receptor ligands and is required for proper cholesterol homeostasis and Aß clearance in human astrocytes.

Effects of mild running on substantia nigra during early neurodegeneration.

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H2O2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.

Effects of mild running on substantia nigra during early neurodegeneration

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8weeks) and 6weeks of moderate treadmill running, beginning 4weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H2O2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.

Effects of mild running on substantia nigra during early neurodegeneration

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8weeks) and 6weeks of moderate treadmill running, beginning 4weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H2O2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.