Is Chronic Systemic Inflammation a Determinant Factor in Developing Parkinson’s Disease?

The etiology of Parkinson’s disease (PD) is complex and involves numerous risk factors as environmental and hereditary. Nevertheless, recent studies have established that systemic inflammation and neuroinflammation are both present in the prodromal phase and sustained during the progression of the disease. Evidence suggests that the activation of the peripheral immune system exacerbates the brain inflammatory response, which may initiate or enhance neurodegenerative processes. Understanding the impact of chronic systemic inflammation in the neuroinflammation and the progression of the disease will provide a broader view of the etiology and pathology of PD. In this chapter, we review the role of the chronic systemic inflammation in neuroinflammation and its effect on PD, considering cell types, molecular, and inflammatory mediators that predispose to the development of the disease

La alteración hipotalámica en la obesidad

The hypothalamus is the primary neuroendocrine regulator center in the context of energetic balance homeostasis and hunger. Misfunction or direct damage in the hypothalamic nucleus generates energy expenditure and intake impairments, which drive accelerated weight gain. Diverse neuronal populations, particularly in the hypothalamic arcuate nucleus, detect nutritional needs and integrate peripheral hormone signaling, including pancreatic-derived insulin and adipocyte-derived leptin, to modulate calorie intake, glucose metabolism, and energy homeostasis. In Mexico, obesity levels have increased alarmingly in recent decades, and worldwide it is considered a public health problem, so it is required a better comprehension of the major weight gain causes and its related comorbidities, such as type 2 diabetes mellitus, among others, to give a solution to this problem. This review focuses on the general description of the central nervous system-dependent energetic homeostasis regulation and illustrates how the neuronal circuits are dysregulated in obesity, driving overnutrition and energy imbalance.El hipotálamo es el centro de regulación neuroendocrina de la homeostasis energética y del apetito. El mal desarrollo o el daño a los núcleos hipotalámicos involucrados alteran el equilibrio entre ingesta y gasto de energía, lo que conduce a un rápido aumento de peso. Distintas poblaciones neuronales, particularmente del núcleo arqueado del hipotálamo, detectan el estado nutricional del organismo e integran señales de hormonas periféricas, incluidas la insulina producida en el páncreas y la leptina, derivada de los adipocitos para regular la ingesta de calorías, el metabolismo de la glucosa y el gasto de energía. En México los niveles de obesidad se han incrementado de forma alarmante en las últimas décadas y mundialmente se considera un problema de salud pública, por lo que, para dar solución a este problema se requiere de una mejor comprensión de las causas subyacentes del aumento de peso y sus comorbilidades metabólicas asociadas como la diabetes mellitus tipo 2, entre otras. Esta revisión se enfoca en la descripción general de la regulación dependiente de la homeostasis energética del sistema nervioso central ilustra cómo la desregulación de los circuitos neuronales involucrados puede conducir a la sobre nutrición y la obesidad

The hypotalamic disturbances during obesity: neuroinflammation and metabolic dysfunction/La alteración hipotalámica en la obesidad: neuroinflamación y disfunción metabólica

     La obesidad es considerada actualmente como un problema de salud pública global y se caracteriza por la hipertrofia e hiperplasia del tejido adiposo debido a la ingesta hipercalórica y la falta de actividad física, desarrollando disfunción metabólica, inflamación sistémica crónica de bajo grado y gradualmente neuroinflamación hipotalámica. El tejido adiposo actúa como un órgano endocrino secretando adipocinas y citocinas alrededor de los órganos periféricos, actuando como regulador del metabolismo, sin embargo, la presencia de niveles elevados de ácidos grasos libres y de moléculas inflamatorias derivadas de los adipocitos, pueden alterar la respuesta inmunitaria sistémica, generando inflamación crónica, comprometiendo la integridad de la barrera hemato-encefálica y estimulando la respuesta de la glía, especialmente en regiones específicas del hipotálamo, centro de regulación de la homeostasis energética. Las células gliales hipotalámicas son importantes en la transmisión de señales inflamatorias relacionadas con la dieta y pueden modular la actividad neuronal, así como responder a las señales inmunológicas periféricas e iniciar la inflamación local y gliosis. Esta revisión se enfoca en la descripción general de la disfunción metabólica asociada a la obesidad y su participación en la alteración de la regulación hipotalámica, provocando neuroinflamación y modificaciones en la conducta alimentaria

Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats

Being overweight and obesity are world health problems, with a higher prevalence in women, defined as abnormal or excessive fat accumulation that increases the risk of chronic diseases. Excess energy leads to adipose expansion, generating hypertrophic adipocytes that produce various pro-inflammatory molecules. These molecules cause chronic low-intensity inflammation, affecting the organism’s functioning and the central nervous system (CNS), inducing neuroinflammation. The neuroinflammatory response during obesity occurs in different structures of the CNS involved in memory and learning, such as the cortex and the hippocampus. Here we analyzed how obesity-related peripheral inflammation can affect CNS physiology, generating neuroinflammation and promoting cellular senescence establishment. Since some studies have shown an increase in senescent cells during aging, obesity, and neurodegenerative diseases, we proposed that cellular senescence participation may contribute to the cognitive decline in an obesity model of middle-aged female Wistar rats. The inflammatory state of 6 and 13 months-old female Wistar rats fed with a hypercaloric diet was measured in serum and CNS (cortex and hippocampus). Memory was evaluated using the novel object recognition (NOR) test; the presence of senescent markers was also determined. Our data suggest that the systemic inflammation generated by obesity induces a neuroinflammatory state in regions involved in learning and memory, with an increase in senescent markers, thus proposing senescence as a potential participant in the negative consequences of obesity in cognition

Chronic Systemic Inflammation Exacerbates Neurotoxicity in a Parkinson’s Disease Model

Systemic inflammation is a crucial factor for microglial activation and neuroinflammation in neurodegeneration. This work is aimed at assessing whether previous exposure to systemic inflammation potentiates neurotoxic damage by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and how chronic systemic inflammation participates in the physiopathological mechanisms of Parkinson’s disease. Two different models of systemic inflammation were employed to explore this hypothesis: a single administration of lipopolysaccharide (sLPS; 5 mg/kg) and chronic exposure to low doses (mLPS; 100 μg/kg twice a week for three months). After three months, both groups were challenged with MPTP. With the sLPS administration, Iba1 staining increased in the striatum and substantia nigra, and the cell viability lowered in the striatum of these mice. mLPS alone had more impact on the proinflammatory profile of the brain, steadily increasing TNFα levels, activating microglia, reducing BDNF, cell viability, and dopamine levels, leading to a damage profile similar to the MPTP model per se. Interestingly, mLPS increased MAO-B activity possibly conferring susceptibility to MPTP damage. mLPS, along with MPTP administration, exacerbated the neurotoxic effect. This effect seemed to be coordinated by microglia since minocycline administration prevented brain TNFα increase. Coadministration of sLPS with MPTP only facilitated damage induced by MPTP without significant change in the inflammatory profile. These results indicate that chronic systemic inflammation increased susceptibility to MPTP toxic effect and is an adequate model for studying the impact of systemic inflammation in Parkinson’s disease

A Potential Alternative against Neurodegenerative Diseases: Phytodrugs

Neurodegenerative diseases (ND) primarily affect the neurons in the human brain secondary to oxidative stress and neuroinflammation. ND are more common and have a disproportionate impact on countries with longer life expectancies and represent the fourth highest source of overall disease burden in the high-income countries. A large majority of the medicinal plant compounds, such as polyphenols, alkaloids, and terpenes, have therapeutic properties. Polyphenols are the most common active compounds in herbs and vegetables consumed by man. The biological bioactivity of polyphenols against neurodegeneration is mainly due to its antioxidant, anti-inflammatory, and antiamyloidogenic effects. Multiple scientific studies support the use of herbal medicine in the treatment of ND; however, relevant aspects are still pending to explore such as metabolic analysis, pharmacokinetics, and brain bioavailability

Neurocysticercosis: local and systemic immune-inflammatory features related to severity.

International audienceNeurocysticercosis (NC) is caused by the establishment of Taenia solium cysticerci in the central nervous system. Previous studies have established that neuroinflammation plays a key role in the severity of the disease. However, the relationship between peripheral and local immune response remains inconclusive. This work studies the peripheral and local immune-inflammatory features and their relationships, toward the identification of potential peripheral immunologic features related to severity. A panel of cytokines was measured in paired cerebrospinal fluid (CSF) and in the supernatant of antigen-specific stimulated peripheral blood mononuclear cells samples (SN) in a total of 31 untreated inflammatory and non-inflammatory NC patients. Increased clinical and radiologic severity was associated with an increased cerebrospinal fluid cell count. A peripheral proliferative depression that negatively correlates with CSF cellularity and TNFα and that positively correlates with SN IL5 was observed in severe NC patients. These results provide evidences to support the systemic proliferative response as a biomarker to monitor the level of neuroinflammation, of possible value in the patients' follow-up during treatment

Image_1_Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats.TIFF

Being overweight and obesity are world health problems, with a higher prevalence in women, defined as abnormal or excessive fat accumulation that increases the risk of chronic diseases. Excess energy leads to adipose expansion, generating hypertrophic adipocytes that produce various pro-inflammatory molecules. These molecules cause chronic low-intensity inflammation, affecting the organism’s functioning and the central nervous system (CNS), inducing neuroinflammation. The neuroinflammatory response during obesity occurs in different structures of the CNS involved in memory and learning, such as the cortex and the hippocampus. Here we analyzed how obesity-related peripheral inflammation can affect CNS physiology, generating neuroinflammation and promoting cellular senescence establishment. Since some studies have shown an increase in senescent cells during aging, obesity, and neurodegenerative diseases, we proposed that cellular senescence participation may contribute to the cognitive decline in an obesity model of middle-aged female Wistar rats. The inflammatory state of 6 and 13 months-old female Wistar rats fed with a hypercaloric diet was measured in serum and CNS (cortex and hippocampus). Memory was evaluated using the novel object recognition (NOR) test; the presence of senescent markers was also determined. Our data suggest that the systemic inflammation generated by obesity induces a neuroinflammatory state in regions involved in learning and memory, with an increase in senescent markers, thus proposing senescence as a potential participant in the negative consequences of obesity in cognition.</p