Mitochondrial Aging and Metabolism: The Importance of a Good Relationship in the Central Nervous System

The mitochondrial theory of aging suggests that mitochondria have a decrease in production capacity of adenosine triphosphate (ATP). The question may seem trivial, but it becomes more complex when considering that dysfunctional mitochondria can be eliminated by lysosomal digestion and that cell with dysfunctional mitochondria can undergo the process of apoptosis. In organs with regenerative capacity, like the liver, cell proliferation can almost completely hide mitochondrial dysfunction. However, evidence indicates selective damage in mitochondria during aging, and so the mitochondrial aging theory is gaining recognition and respect. There is solid evidence that accumulated DNA damage in mitochondria is a cause directly related to metabolic disorders such as diabetes and degenerative disorders such as Alzheimer’s disease. The central nervous system is particularly susceptible to oxidative damage due to several factors, among which are its high oxygen consumption, its dependence on aerobic carbohydrate metabolism, and its complex composition of membrane lipids. Free radicals are generated at many cell sites, and the mitochondrial respiratory chain is one of the main sources. While many studies have been conducted in experimental animal models, the results are relevant because at least some of their interventions suggest a directing aim at reducing the effects of aging

Gut-Brain Axis: Role of Microbiota in Parkinson’s Disease and Multiple Sclerosis

It has recently been discovered that the digestive tract is lined with about 100 million nerve cells; the digestive tract has been baptized, metaphorically speaking, as “the second brain,” which contains a multitude of neurotransmitters, viruses, and bacteria that help regulate our emotional state. This second brain, known as the enteric nervous system, is a unique anatomical unit that extends from the esophagus to the anus. Like the nervous system, it produces a whole series of psychoactive substances, such as serotonin, dopamine, and opioids for pain, and synthesizes benzodiazepines. In it, we find the microbiota: a set of microorganisms (viruses and bacteria). Together with the brain, the microbiota directly influences mood, character, or sleep. Knowledge about the possible relationship of the microbiota with frequent neurological diseases is still just beginning. Recently, possible changes in the microbiota have been linked to the onset of Parkinson’s disease (PD). Also, today, we know that there are differences between the microbiota of healthy people and people with multiple sclerosis and that these differences have also been related to the disease and its evolution

Oxidative Stress and Parkinson’s Disease: Effects on Environmental Toxicology

Epidemiological studies have found an increased risk of Parkinson’s disease (PD) with environmental factors such as exposure to substances derived from industrial processes, use of agrochemicals, or living in a rural environment. The hypothesis that certain environmental toxins could be the source of the EP is supported by the discovery that chemicals such as herbicides paraquat, diquat, and the fungicide maneb are selectively toxic in nigrostriatal dopaminergic neurons. Also, one of the insecticides produced by plants, such as rotenone, and by-product of the synthesis of synthetic heroin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can be reproduced in animal models where neurochemicals, histopathological, and clinical characteristic of PD can be found. Interestingly, there are similarities in the chemical structure of paraquat and MPTP. Recent evidence exhibited that inflammation and oxidative stress play an essential role in the development of PD. So, in our laboratory we found that in an animal model melatonin decreases the products of lipid oxidation, nitric oxide metabolites, and the activity of cyclooxygenase 2, which are induced by an intraperitoneal injection of MPTP. This suggests that the neuroprotective effects of melatonin are partially attributed to its antioxidant scavenging and anti-inflammatory action

Physiology and Pathology of Neuroimmunology: Role of Inflammation in Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease that affects 1% of the population aged 65 and over and is the second most common neurodegenerative disease next to Alzheimer’s disease. Interneuronal proteinaceous inclusions called Lewy bodies (LB) and a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNPC) are the main features of PD pathology. The most common clinical manifestations are rigidity, tremor, bradykinesia, postural instability, sleep disorders, alterations in gait, smell, memory, and dementia. Genetic and environmental factors are involved in PD, and, recently, oxidative stress, proteasome-mediated protein degradation, and inflammation have acquired relevance as major mechanisms of neuronal dysfunction. Increased levels of reactive oxygen and nitrogen species in the brain contribute to greater vulnerability of proteins to nitro-oxidative modification and to greater degrees of aggregation. These protein aggregates contain a variety of proteins of which α-synuclein appears to be the main structural component. Interestingly, α-synuclein can be secreted by neuronal cells and may lead the initiation and the maintenance of inflammatory events through the activation of microglia, which contributes to dopaminergic neuron depletion. New evidence also suggests that PD may be the result of an autoimmune response in which the immune cells recognize the neurons as foreign elements and would act against them, causing their death

Multiple Sclerosis and Its Relationship with Oxidative Stress, Glutathione Redox System, ATPase System, and Membrane Fluidity

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a focus on inflammation, demyelination, and damage to axons leading to neurological deficits. MS pathology is associated with excessive reactive oxygen species (ROS) and generation of reactive nitrogen species (RNS), causing oxidative/nitrosative stress. Deregulation of glutathione homeostasis and alterations in glutathione‐dependent enzymes are implicated in MS. Reactive oxygen species enhance both monocyte adhesion and migration across brain endothelial cells. In addition, ROS can activate the expression of the nuclear transcription factor‐kappa, which upregulates the expression of many genes involved in MS, such as tumor necrosis factor‐α and nitric oxide synthase, among others, leading to mitochondrial dysfunction and energy deficits that result in mitochondrial and cellular calcium overload. Loss of mitochondrial membrane potential can increase the release of cytochrome c, one pathway that leads to neuronal apoptosis. Clinical studies suggest that omega‐3 long‐chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti‐inflammatory, antioxidant, and neuroprotective effects in MS and animal models of MS. Here, we review the relationship of oxidative stress, the glutathione redox system, the ATPase system, and membrane fluidity with the development of MS. In addition, we describe the main findings of a clinical trial conducted with relapsing‐remitting MS patients who received a diet supplemented with 4 g/day of fish oil or olive oil. The effects of PUFAs supplementation on the parameters indicated above are analyzed in this work

Frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico.

BACKGROUND: Between 29% and 67% of neuromyelitis optica spectrum disorder patients have cognitive alterations. OBJECTIVE: To assess the frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico using the Brief International Cognitive Assessment for Multiple Sclerosis. METHODS: We evaluated 40 neuromyelitis optica spectrum disorder patients and 40 healthy controls from Mexico. RESULTS: 28 (70.0%) patients with neuromyelitis optica spectrum disorder had cognitive impairment in two or more cognitive domains. Student´s T test showed statistically poor performance by neuromyelitis optica spectrum disorder patients compared to healthy controls on all three neuropsychological test scores. This significant difference was observed on the Symbols Digit Modalities Test (t = 8.875; p ≤ 0.001); California Verbal Learning Test-II memory (t = 10.418; p ≤ 0.001); and Brief Visuospatial Memory Test Revised (t = 6.123; p ≤ 0.001). CONCLUSIONS: This study showed that 70% of neuromyelitis optica spectrum disorder patients exhibited cognitive impairment in two or more cognitive domains. Determining the frequency of cognitive impairment will guide the decision of Neuropsychologists in planning cognitive rehabilitation across various domains

Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma.El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática

Effect of Rituximab Compared with Natalizumab and Fingolimod in Patients with Relapsing–Remitting Multiple Sclerosis: A Cohort Study

The objective of this study was to evaluate the clinical files of patients with RRMS who started rituximab (RTX) compared with a second-line treatment (natalizumab (NTZ) or fingolimod (FTY)). This was a historical cohort study. We compared the effect according to the Expanded Disability Status Scale (EDSS) and the number of relapses in RRMS patients receiving these treatments after a mean period of 12 months. We found a statistically significant difference (p < 0.001) when comparing the EDSS scores and the annual relapse rates of patients receiving RTX with those receiving NTZ or FTY. This study is essential for our clinical practice, since patients with limited treatment options represent a challenge with regard to the management of their medical care. However, clinical trials and prospective studies with long follow-up periods are necessary to provide sufficient evidence on the efficacy of RTX and thus include this treatment in the therapeutic profile of patients with MS