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Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.

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Psychoneuroendocrinoimmunology is the area of study of the intimate relationship between immune, physical, emotional, and psychological aspects. This new way of studying the human body and its diseases was initiated in the last century's first decades. However, the molecules that participate in the communication between the immune, endocrine, and neurological systems are still being discovered. This paper aims to describe the development of psychoneuroendocrinoimmunology, its scopes, limitations in actual medicine, and the extent of melatonin within it.

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Insulin, a key pleiotropic hormone, regulates metabolism through several signaling pathways in target tissues including skeletal muscle, liver, and brain. In the brain, insulin modulates learning and memory, and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases. At the receptor level, in aging and Alzheimer's disease (AD) models, the amount of insulin receptors and their functions are decreased. Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels. Furthermore, diabetes mellitus (DM) and insulin resistance are associated with age-related cognitive decline, increased levels of ß-amyloid peptide, phosphorylation of tau protein; oxidative stress, pro-inflammatory cytokine production, and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mild obesity and insulin resistance without influencing brain size and apoptosis development. Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size and development, and contributes to behavior changes. Insulin is synthesized locally in the brain and is released from the neurons. Here, we reviewed proposed pathophysiological hypotheses to explain increased risk of dementia in the presence of DM. Regardless of the exact sequence of events leading to neurodegeneration, there is strong evidence that mitochondrial dysfunction plays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrial dysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable to those induced in wild-type mice treated with sucrose, which is consistent with the proposal that mitochondrial alterations are associated with DM and contribute to AD development. Alterations in insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidant capacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing and systemic metabolism, and could be a specific target for therapeutic strategies to decrease alterations associated with age-related cognitive decline.

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BACKGROUND: The region of La Cienega in Jalisco Mexico, is an important agricultural reference for the production of corn, sorghum and wheat, among other grains, so the use of pesticides for pest control is high. However, in this rural area there are no toxicological studies that assess the occupational risk of pesticide use. Therefore, this study is the first to determine the oxidative stress levels markers (GSH, GSSG, carbonyl groups, nitric oxide metabolites and lipid peroxides) as well as alteration of the mitochondrial membrane fluidity caused by occupational exposure to organophosphorus and carbamates in farmers of this region. This occupational risk can increase cellular oxidation, which explains the high prevalence of neurodegenerative diseases and cancer in Cienega settlers to be analyzed in future studies. METHODS: Comparative cross-sectional study was performed using two groups: one not exposed group (n = 93) and another one with occupational exposure (n = 113). The latter group was sub-divided into 4 groups based on duration of use/exposure to pesticides. Oxidative stress levels and membrane fluidity were assessed using spectrophotometric methods. Statistical analyses were performed using SPSS software ver. 19.0 for windows. RESULTS: The most commonly used pesticides were organophosphorus, carbamates, herbicide-type glyphosate and paraquat, with an average occupational exposure time of 35.3 years. There were statistically significant differences in markers of oxidative stress between exposed farmers and not exposed group (p = 0.000). However, in most cases, no significant differences were found in markers of oxidative stress among the 4 exposure sub-groups (p > 0.05). CONCLUSION: In the Cienega region, despite the indiscriminate use of organophosphorus and carbamates, there are no previous studies of levels oxidative stress. The results show increased levels of oxidative stress in occupationally exposed farmers, particularly membrane fluidity levels increased three times in contrast to not exposed group.

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BACKGROUND: Karwinskia humboldtiana (Kh) is a poisonous plant of the rhamnacea family. To elucidate some of the subcellular effects of Kh toxicity, membrane fluidity and ATPase activities as hydrolytic and as proton-pumping activity were assessed in rat liver submitochondrial particles. Rats were randomly assigned into control non-treated group and groups that received 1, 1.5 and 2 g/Kg body weight of dry powder of Kh fruit, respectively. Rats were euthanized at day 1 and 7 after treatment. RESULTS: Rats under Kh treatment at all dose levels tested, does not developed any neurologic symptoms. However, we detected alterations in membrane fluidity and ATPase activity. Lower dose of Kh on day 1 after treatment induced higher mitochondrial membrane fluidity than control group. This change was strongly correlated with increased ATPase activity and pH gradient driven by ATP hydrolysis. On the other hand, membrane fluidity was hardly affected on day 7 after treatment with Kh. Surprisingly, the pH gradient driven by ATPase activity was significantly higher than controls despite an diminution of the hydrolytic activity of ATPase. CONCLUSIONS: The changes in ATPase activity and pH gradient driven by ATPase activity suggest an adaptive condition whereby the fluidity of the membrane is altered.

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BACKGROUND: Karwinskia humboldtiana (Kh) is a poisonous plant of the rhamnacea family. To elucidate some of the subcellular effects of Kh toxicity, membrane fluidity and ATPase activities as hydrolytic and as proton-pumping activity were assessed in rat liver submitochondrial particles. Rats were randomly assigned into control non-treated group and groups that received 1,1.5 and 2 g/Kg body weight of dry powder of Kh fruit, respectively. Rats were euthanized at day 1 and 7 after treatment. RESULTS: Rats under Kh treatment at all dose levels tested, does not developed any neurologic symptoms. However, we detected alterations in membrane fluidity and ATPase activity. Lower dose of Kh on day 1 after treatment induced higher mitochondrial membrane fluidity than control group. This change was strongly correlated with increased ATPase activity and pH gradient driven by ATP hydrolysis. On the other hand, membrane fluidity was hardly affected on day 7 after treatment with Kh. Surprisingly, the pH gradient driven by ATPase activity was significantly higher than controls despite an diminution of the hydrolytic activity of ATPase. CONCLUSIONS: The changes in ATPase activity and pH gradient driven by ATPase activity suggest an adaptive condition whereby the fluidity of the membrane is altered.

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Background. Dementia affects memory, thinking, language, judgment, and behavior. Depression, is common in older adults with dementia. The concomitance of dementia and depression increases disability with impaired activities of daily living (ADL), increasing the chances of institutionalization and mortality. Methods. Cross-sectional study of a population 60 years and older who live in the State of Jalisco, Mexico. A total of 1142 persons were assessed regarding their cognitive function, emotional state, and physical performance. Door-to-door interview technique was assigned in condition with multistage probability random sampling. Cognitive function, depression and functional disability were assessed by applying standardized Minimental State Examination (Folstein), Geriatric Depression Scale, and the Katz index, respectively. Diagnosis of dementia was performed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, the Fourth Edition. Data were analyzed using SPSS software. Results. Prevalence of demency was 9.5% (63.35% women, and 36.7% men). Demency was associated with being woman, being older than 70 years, low level of education, not having the economic benefit of retirement, being single or living without a partner, low level of education, suffering from depression and have functional disability in ADL. Conclusion. Dementia is more common in women and is related to depression and disability.

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INTRODUCTION: The feeding behavior establishes a relation of humans with food, includes food habits that could be involved with oxidative stress. OBJECTIVE: To evaluate the relation of indicators of oxidative stress (lipid peroxides) and antioxidant (ascorbic acid, catalase, superoxide dismutase) with feeding behavior in adults of Teocuhitatlan Corona, Jalisco, Mexico. METHOD: Study observational, descriptive, cross-sectional of 44 adults with 43 to 88 years, was used a instrument of feeding behavior. The questionnaire were related to indicators of oxidative stress. Were used descriptive statistics, frequency distribution and analysis of covariance with adjustment variables, was considered significant p <0.05. RESULTS: The values of serum lipid peroxides were related to behaviors: consider the nutritional content as most important when choosing food (p = 0.042), dislike milk (p = 0.027), intake of sweets between meals (p = 0.001), habitual inclusion of vegetables and salads in main meal (p = 0.018). We do not found association in to values of ascorbic acid, cholesterol in low density lipoproteins and enzymatic activities of catalase and superoxide dismutase with food behaviors. DISCUSSION: The feeding behaviors analyzed in this study may be involved with development of oxidative stress and could be have protective or harmful effect in development to complications of chronic non-communicable diseases and aging in this population. This suggests to analyze demographic and socio-cultural aspects of region and besides analyzing the consumption and metabolic markers related to food.

Introducción: El comportamiento alimentario establece la relación del ser humano con la alimentación, comprende hábitos alimentarios que podrían intervenir en el desarrollo del estrés oxidativo. Objetivos: Evaluar la relación de indicadores de estrés oxidativo (lipoperóxidos) y capacidad antioxidante (ácido ascórbico, catalasa, superóxido dismutasa) con el comportamiento alimentario en adultos que residen en Teocuitatlán de Corona, Jalisco, México. Método: Estudio observacional, descriptivo, transversal, comparativo de 44 adultos de 43 a 88 años de edad. Se aplicó un instrumento de comportamiento alimentario. Los resultados del cuestionario se relacionaron con los indicadores de estrés oxidativo. Se utilizó estadística descriptiva, distribución de frecuencias y análisis de co-varianza con ajuste de variables, se consideró una significancia de p.

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Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

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Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer's Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels.