Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
Add more filters











Publication year range
1.
Parkinsons Dis ; 2024: 5519396, 2024.
Article in English | MEDLINE | ID: mdl-39104613

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder characterized by alterations in motor capacity resulting from a decrease in the neurotransmitter dopamine due to the selective death of dopaminergic neurons of the nigrostriatal pathway. Unfortunately, conventional pharmacological treatments fail to halt disease progression; therefore, new therapeutic strategies are needed, and currently, some are being investigated. The endocannabinoid system (ECS), highly expressed in the basal ganglia (BG) circuit, undergoes alterations in response to dopaminergic depletion, potentially contributing to motor symptoms and the etiopathogenesis of PD. Substantial evidence supports the neuroprotective role of the ECS through various mechanisms, including anti-inflammatory, antioxidative, and antiapoptotic effects. Therefore, the ECS emerges as a promising target for PD treatment. This review provides a comprehensive summary of current clinical and preclinical evidence concerning ECS alterations in PD, along with potential pharmacological targets that may exert the protection of dopaminergic neurons.

2.
Heliyon ; 10(6): e27468, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38509984

ABSTRACT

Background: Cardiorenal syndrome (CRS) type 4 is prevalent among the chronic kidney disease (CKD) population, with many patients dying from cardiovascular complications. However, limited data regarding cardiac transcriptional changes induced early by CKD is available. Methods: We used a murine unilateral ureteral obstruction (UUO) model to evaluate renal damage, cardiac remodeling, and transcriptional regulation at 21 days post-surgery through histological analysis, RT-qPCR, RNA-seq, and bioinformatics. Results: UUO leads to significant kidney injury, low uremia, and pathological cardiac remodeling, evidenced by increased collagen deposition and smooth muscle alpha-actin 2 expression. RNA-seq analysis identified 76 differentially expressed genes (DEGs) in UUO hearts. Upregulated DEGs were significantly enriched in cell cycle and cell division pathways, immune responses, cardiac repair, inflammation, proliferation, oxidative stress, and apoptosis. Gene Set Enrichment Analysis further revealed mitochondrial oxidative bioenergetic pathways, autophagy, and peroxisomal pathways are downregulated in UUO hearts. Vimentin was also identified as an UUO-upregulated transcript. Conclusions: Our results emphasize the relevance of extensive transcriptional changes, mitochondrial dysfunction, homeostasis deregulation, fatty-acid metabolism alterations, and vimentin upregulation in CRS type 4 development.

3.
Brain Res ; 1793: 148055, 2022 10 15.
Article in English | MEDLINE | ID: mdl-35985361

ABSTRACT

Early life stress induced by maternal separation (MS) causes neuroendocrine, behavioral, and metabolic alterations that are related to gut dysbiosis. MS also increases microglial activation and decreases neurogenesis. Whether these long-term alterations are maintained or worsened in the absence of gut microbiota remains unknown. Hence, this study evaluated the effect of MS symptomatology after antibiotic-induced microbiota depletion (AIMD) in adult rats. Control and maternally separated (3 h per day from postnatal day one to 14, MS180) rats were subjected to AIMD for one month, then assessed for behavioral, metabolic, and neuroendocrine responses. Effects of MS180 and AIMD on gut microbiota were confirmed by qPCR. The data indicate that MS180 caused a passive coping strategy in the forced swimming test and decreased hippocampal neurogenesis. In addition, fasting glucose, cholesterol, and corticosterone levels increased, which correlated with a decrease in Lactobacillus spp counts in the caecum. AIMD also increased immobility in the forced swimming test, decreased hippocampal neurogenesis, and augmented corticosterone levels. However, it had no effects on glucose homeostasis or plasma lipid levels. Furthermore, the MS180-induced long-term effects on behavior and neurogenesis were not affected by microbiota depletion. Meanwhile, the metabolic imbalance was partially reversed in MS180 + AIMD rats. These results show that AIMD mimics the behavioral consequences of MS180 but may prevent metabolic imbalance, suggesting that gut dysbiosis could be part of the mechanisms involved in the maintenance of the long-term consequences of early life stress.


Subject(s)
Microbiota , Stress, Psychological , Animals , Rats , Anti-Bacterial Agents/pharmacology , Behavior, Animal/physiology , Corticosterone , Dysbiosis , Glucose/metabolism , Hypothalamo-Hypophyseal System/metabolism , Maternal Deprivation , Pituitary-Adrenal System/metabolism
4.
Article in English | MEDLINE | ID: mdl-34769555

ABSTRACT

Landfill leachate is a complex mixture of organic and inorganic molecules, as well as environmental pollutants that can cause harm to ecosystems and living beings. The micronucleus test in peripheral blood erythrocytes was used to evaluate the genotoxic and cytotoxic effects of exposure to a landfill leachate from an outdoor solid waste storage system on Wistar strain rats at different developmental stages, pre-adolescents and young adults, and the heavy metal content of the leachate was determined by atomic absorption spectrometry. Contents of arsenic, cadmium, chromium, mercury, and lead in the landfill leachate were outside the allowable international standards, and the exposure to the landfill leachate caused genotoxic and cytotoxic effects on Wistar rats, where the pre-adolescent animals were more susceptible to the toxics contained in the landfill leachate than young adults. Heavy metals contained in landfill leachate, individually or synergically with other molecules can be responsible for clastogenic and cytotoxic effects that can be harmful to humans and ecosystems.


Subject(s)
Refuse Disposal , Water Pollutants, Chemical , Animals , DNA Damage , Ecosystem , Rats , Rats, Wistar , Solid Waste/analysis , Waste Disposal Facilities , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
5.
J Med Food ; 22(5): 460-468, 2019 May.
Article in English | MEDLINE | ID: mdl-30864870

ABSTRACT

Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required. ß-caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders. For this reason, we assessed whether BCP modulates nociception, anxiety, and depressive-like behavior in streptozotocin (STZ)-induced experimental diabetic BALB/c female mice. BCP was orally chronic administrated (10 mg/kg/60 µL). Pain developed with STZ was evaluated with von Frey filament test, SMALGO®, and hot plate test. Anxiety and depression-like behavior were assessed by marbles test, forced swim test, and tail suspension test. BCP significantly reduced glycemia in experimental diabetic mice. The pain was also mitigated by BCP administration. Depression-like behavior assessed with tail suspension test was attenuated with orally chronic BCP administration. Substance P and cytokines such as interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were also attenuated with BCP administration. NP was positively correlated with substance P and IL-6 and IL-1ß release. Our data using an orally chronic BCP administration in the STZ challenged mice to suggest that glycemia, diabetes-related NP, and depressive-like behavior could be prevented/reduced by dietary BCP.


Subject(s)
Diabetes Mellitus, Experimental/complications , Neuralgia/drug therapy , Neuralgia/psychology , Sesquiterpenes/administration & dosage , Animals , Anxiety , Behavior, Animal/drug effects , Depression , Female , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Mice , Mice, Inbred BALB C , Neuralgia/etiology , Neuralgia/metabolism , Polycyclic Sesquiterpenes , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
6.
J Agric Food Chem ; 65(43): 9435-9442, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28942644

ABSTRACT

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and Piper longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1% inhibition of inflammatory pain at 2.5 mg/kg ip and 50.0 ± 15.9% inhibition of edema formation at 5 mg/kg ip) and acute analgesia (66.1 ± 28.1% inhibition at 5.0 mg/kg ip) were observed. Moreover, guineensine inhibited proinflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy, but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant, but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels, and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A, and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.


Subject(s)
Alkenes/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Edema/drug therapy , Endocannabinoids/metabolism , Heterocyclic Compounds, 2-Ring/administration & dosage , Inflammation/drug therapy , Piper nigrum/chemistry , Plant Extracts/administration & dosage , Animals , Edema/metabolism , Endocannabinoids/antagonists & inhibitors , Humans , Inflammation/metabolism , Male , Mice , Mice, Inbred BALB C , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Seeds/chemistry
7.
Pediatr Neonatol ; 58(1): 70-76, 2017 02.
Article in English | MEDLINE | ID: mdl-27522459

ABSTRACT

BACKGROUND: Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1ß and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. METHODS: The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). RESULTS: The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. CONCLUSION: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.


Subject(s)
Asphyxia Neonatorum/blood , Cytokines/blood , Hypoxia-Ischemia, Brain/blood , Phosphopyruvate Hydratase/blood , S100 Proteins/blood , Asphyxia Neonatorum/complications , Biomarkers/blood , Case-Control Studies , Electroencephalography , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hypoxia-Ischemia, Brain/diagnosis , Hypoxia-Ischemia, Brain/etiology , Infant , Infant, Newborn , Male , Pregnancy , Prognosis , Sensitivity and Specificity
8.
J Mol Neurosci ; 56(2): 245-54, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25854776

ABSTRACT

Excitotoxicity and neuroinflammation are strongly linked to the progressions of neurodegenerative diseases and acute injuries in the brain. Systematic administration of kainic acid (KA) in rodents causes severe limbic seizures, selective neuronal loss, and neuroinflammation in the hippocampus that are attributed to the excitotoxic process. Our previous report demonstrated the antioxidant and neuroprotective effects of pirfenidone (PFD) after the seizure onset induced by KA intraperitoneal injection. However, the aim of the present study is to analyze whether PFD has anti-inflammatory properties. Thus, pubescent male Wistar rats (30 days old) were exposed to 12 mg/Kg of KA, and the experimental group received KA and a single dose of 325 mg/Kg PFD in an orogastric tube at 90 min after KA exposure. The PFD treatment dramatically reduces the microglial activation observed by isolectin B4 staining and major histocompatibility complex II immunohistochemistry. We also determined that the messenger RNA of inducible nitric oxide synthase was downregulated by PFD treatment as measured 6 h after the KA injection. Our results indicate that the mechanism of neuroprotection after PFD treatment may include a decreased expression of the inducible nitric oxide synthase and reduced microglial activation. These findings suggest that PFD is a potentially useful strategy of the treatment for acute or chronic neurodegenerative diseases.


Subject(s)
Hippocampus/drug effects , Microglia/drug effects , Neuroprotective Agents/pharmacology , Nitric Oxide Synthase Type II/metabolism , Pyridones/pharmacology , Animals , Hippocampus/cytology , Hippocampus/growth & development , Hippocampus/metabolism , Kainic Acid/toxicity , Male , Microglia/metabolism , Nitric Oxide Synthase Type II/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar
9.
J Mol Neurosci ; 52(2): 193-201, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24142572

ABSTRACT

Systemic administration of kainic acid (KA) in rodents triggers limbic seizures following selective neuronal loss in the hippocampus attributed to the excitotoxic process. Lipid peroxidation products, such as 4-hydroxynonenal, are produced by oxidative stress and are present on the hippocampus, which contribute to neuronal death in the KA excitotoxicity model. Several antioxidants are neuroprotective agents. The aim of the present study was to analyse whether pirfenidone (PFD, 5-methyl-1-phenyl-2-(1H)-pyridone), an antioxidant drug, protects the neurons in the hippocampus of pubescent rats administered with KA. We evaluated the neuroprotective effect of PFD by quantifying the surviving neurons under hematoxilin-eosin staining after using three different doses of 100, 250, and 325 mg/kg administered via an orogastric tube 90 min after KA intraperitoneal injection (12 mg/kg). Only 325 mg/kg of PFD-attenuated neuronal loss in the hippocampal areas cornu ammonis field 1 (CA1) and cornu ammonis field 3 (CA3c) was observed; therefore, this dose was used in our subsequent studies. Later, we established that PFD reduces neuronal degeneration using Fluoro-Jade B stain in the CA3c but not in the CA1, and PFD reduces the presence of 4-hydroxynonenal, a lipid peroxidation product, in the CA3 by tissue immunohistochemistry. We concluded that only a single 325 mg/kg PFD dose had a neuroprotective effect after KA brain injury. This treatment may be advantageous because adequate pharmacological therapy with PFD can be developed to protect the neuron even after an acute neuronal disorder such as seizures or hypoxic/ischemic damage.


Subject(s)
Antioxidants/pharmacology , Lipid Peroxidation , Neurons/drug effects , Neuroprotective Agents/pharmacology , Pyridones/pharmacology , Action Potentials , Animals , Cell Death , Cell Survival , Dose-Response Relationship, Drug , Hippocampus/cytology , Hippocampus/growth & development , Kainic Acid/toxicity , Male , Neurons/metabolism , Neurons/physiology , Rats , Rats, Wistar
10.
Curr Pharm Des ; 19(38): 6709-19, 2013.
Article in English | MEDLINE | ID: mdl-23530508

ABSTRACT

Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system, and interacts with two classes of receptor: metabotropic and ionotropic receptors. Ionotropic receptors are divided according to the affinity of their specific agonists: Nmethyl- D-aspartate (NMDA), amino acid-3-hydroxy-5-methyl-4-isoxazole acid (AMPA) and kainic acid (KA). NMDA receptors (NMDA-R) are macromolecular structures that are formed by different combinations of subunits: NMDAR1 (NR1), NMDAR2 (NR2) and NMDAR3 (NR3). The study of this receptor has aroused great interest, partly due to its role in synaptic plasticity but mainly because of its permeability to the Ca(2+) ion. This review examines the molecular composition of NMDA-R and the variants of NR1 subunit editing in association with NR2 subunit dimers, which form the main components of this receptor. Their composition, structure, function and distinct temporal and spatial expression patterns demonstrate the versatility and diversity of functionally different isoforms of NR1 subunits and the various pharmacological properties of the NR2 subunit. Finally, the involvement of NMDA-R in the excitotoxicity phenomenon, as well as, its expression changes under these conditions as neuronal response are also discussed.


Subject(s)
Receptors, N-Methyl-D-Aspartate/physiology , Alzheimer Disease/physiopathology , Animals , Humans , Huntington Disease/physiopathology , Protein Isoforms/metabolism , Receptors, N-Methyl-D-Aspartate/chemistry , Receptors, N-Methyl-D-Aspartate/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL