RIPK2 Is Crucial for the Microglial Inflammatory Response to Bacterial Muramyl Dipeptide but Not to Lipopolysaccharide.

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is a kinase that is essential in modulating innate and adaptive immune responses. As a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs), it is implicated in the signaling triggered by recognition of microbe-associated molecular patterns by NOD1/2 and TLRs. Upon activation of these innate immune receptors, RIPK2 mediates the release of pro-inflammatory factors by activating mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB).

Bacterial Lipopolysaccharide Post-Conditioning in The kainic acid animal model of Temporal Lobe epilepsy.

This study used intra-hippocampal injections of Kainic Acid (KA) in Wistar rats to induce spontaneous recurrent seizures (SRS) after a 9-day latent period. A post-conditioning protocol with LPS, injected at the same site 72 h after the initial KA insult, was employed to trigger secondary competing processes. To evaluate the post-conditioning effect of LPS, 25 animals were divided into four groups: SAL-SAL (n = 6), KA-SAL (n = 6), SAL-LPS (n = 7), and KA-LPS (n = 6).

RIPK2 is crucial for the microglial inflammatory response to bacterial muramyl dipeptide but not to lipopolysaccharide.

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is a kinase that plays an essential role in the modulation of innate and adaptive immune responses. As a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs), it is implicated in the signaling triggered by recognition of microbe-associated molecular patterns by NOD1/2 and TLRs. Upon activation of these innate immune receptors, RIPK2 mediates the release of pro-inflammatory factors by activating mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB).

Cannabidiol and epilepsy.

Cannabidiol (CBD) has been investigated as a pharmacological approach for treating a myriad of neurological and psychiatric disorders, the most successful of them being its use as an antiseizure drug (ASD). Indeed, CBD has reached the clinics for the treatment of certain epileptic syndromes. This chapter aims to overview the pharmacology of CBD and its potential mechanisms of action as an ASD.

Genetic ablation of the isoform γ of PI3K decreases antidepressant efficacy of ketamine in male mice.

About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants.

GlyT1 Inhibition by NFPS Promotes Neuroprotection in Amyloid-β-Induced Alzheimer's Disease Animal Model.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β, leading to N-methyl-D-aspartate (NMDA) receptor-dependent synaptic depression, spine elimination, and memory deficits. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission via NMDA receptors (NMDAR), presenting a potential alternative therapeutic approach for AD. This study investigates the neuroprotective potential of GlyT1 inhibition in an amyloid-β-induced AD mouse model.

Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson's Disease.

Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage.

Pharmacological inhibition of receptor-interacting protein kinase 2 (RIPK2) elicits neuroprotective effects following experimental ischemic stroke.

Ischemic stroke induces a debilitating neurological insult, where inflammatory processes contribute greatly to the expansion and growth of the injury. Receptor-interacting protein kinase 2 (RIPK2) is most well-known for its role as the obligate kinase for NOD1/2 pattern recognition receptor signaling and is implicated in the pathology of various inflammatory conditions. Compared to a sham-operated control, ischemic stroke resulted in a dramatic increase in the active, phosphorylated form of RIPK2, indicating that RIPK2 may be implicated in the response to stroke injury.

Anti-Neuroinflammatory Effects of a Macrocyclic Peptide-Peptoid Hybrid in Lipopolysaccharide-Stimulated BV2 Microglial Cells.

Inflammation processes of the central nervous system (CNS) play a vital role in the pathogenesis of several neurological and psychiatric disorders like depression. These processes are characterized by the activation of glia cells, such as microglia. Clinical studies showed a decrease in symptoms associated with the mentioned diseases after the treatment with anti-inflammatory drugs.

Molecular Mechanisms Linking Osteoarthritis and Alzheimer's Disease: Shared Pathways, Mechanisms and Breakthrough Prospects.

Alzheimer's disease (AD) is a progressive neurodegenerative disease mostly affecting the elderly population. It is characterized by cognitive decline that occurs due to impaired neurotransmission and neuronal death. Even though deposition of amyloid beta (Aβ) peptides and aggregation of hyperphosphorylated TAU have been established as major pathological hallmarks of the disease, other factors such as the interaction of genetic and environmental factors are believed to contribute to the development and progression of AD.

Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice.

The factor RasGEF1b is a Ras guanine exchange factor involved in immune responses. Studies have also implicated RasGEF1b in the CNS development. It is still limited the understanding of the role of RasGEF1b in CNS functioning.

Chronic hyperpalatable diet induces impairment of hippocampal-dependent memories and alters glutamatergic and fractalkine axis signaling.

Chronic consumption of hyperpalatable and hypercaloric foods has been pointed out as a factor associated with cognitive decline and memory impairment in obesity. In this context, the integration between peripheral and central inflammation may play a significant role in the negative effects of an obesogenic environment on memory. However, little is known about how obesity-related peripheral inflammation affects specific neurotransmission systems involved with memory regulation.

Chronic infection by atypical strain induces disturbance in microglia population and altered behaviour in mice.

chronic infection is characterized by the establishment of tissue cysts in the brain and increased levels of IFN-γ, which can lead to brain circuitry interference and consequently abnormal behaviour in mice. In this sense, the study presented here sought to investigate the impact of chronic infection by two strains in the brain of infection-resistant mice, as a model for studying the involvement of chronic neuroinflammation with the development of behavioural alterations. For that, male BALB/c mice were divided into three groups: non-infected (Ni), infected with ME49 clonal strain (ME49), and infected with TgCkBrRN2 atypical strain (CK2).

Neuroprotection by the cannabidiol aminoquinone VCE-004.8 in experimental ischemic stroke in mice.

Synthetic cannabidiol (CBD) derivative VCE-004.8 is a peroxisome proliferator-activated receptor gamma (PPARγ) and cannabinoid receptor type 2 (CB) dual agonist with hypoxia mimetic activity. The oral formulation of VCE-004.

Role of Microglia in Psychostimulant Addiction.

The use of psychostimulant drugs can modify brain function by inducing changes in the reward system, mainly due to alterations in dopaminergic and glutamatergic transmissions in the mesocorticolimbic pathway. However, the etiopathogenesis of addiction is a much more complex process. Previous data have suggested that microglia and other immune cells are involved in events associated with neuroplasticity and memory, which are phenomena that also occur in addiction.

Receptors for Advanced Glycation End Products (RAGE): Promising Targets Aiming at the Treatment of Neurodegenerative Conditions.

Advanced glycation end products (AGEs) are compounds formed after the non-enzymatic addition of reducing sugars to lipids, proteins, and nucleic acids. They are associated with the development of various clinical complications observed in diabetes and cardiovascular diseases, such as retinopathy, nephropathy, diabetic neuropathy, and others. In addition, compelling evidence indicates that these molecules participate in the progression of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.

Background: The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear.

Zones for Fat Grafting in Hybrid Breast Augmentation: Standardization for Planning of Fat Grafting Based on Breast Cleavage Units.

Background: Autologous fat grafting is a procedure indicated for breast augmentation to improve coverage of silicone implants and redesign breast shape. Different techniques are based on parameters that have not been systematically standardized. The authors present a method using breast zone standardization based on breast anatomy to achieve an anatomical composite breast.

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease.

Obesity represents a global health problem and is characterized by metabolic dysfunctions and a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as atherosclerosis, diabetes and insulin resistance. Here we tested the hypothesis that the genetic deletion of metabotropic glutamate receptor 5 (mGluR5) may rescue metabolic and inflammatory features present in BACHD mice, a mouse model of Huntington's disease (HD) with an obese phenotype. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5) in order to obtain the following groups: Wild type (WT), mGluR5, BACHD and BACHD/mGluR5 (double mutant mice).

CB and toll-like receptors crosstalk in microglia.

Microglia play a major role in certain neuropathological conditions. In a recent paper, Reusch et al. demonstrated how signaling pathways downstream of cannabinoid type 2 (CB) and toll-like receptors (TLRs) converge in these cells.

Inhibition of CSF1R, a receptor involved in microglia viability, alters behavioral and molecular changes induced by cocaine.

Different data suggest that microglia may participate in the drug addiction process as these cells respond to neurochemical changes induced by the administration of these substances. In order to study the role of microglia in drug abuse, Swiss mice aged 8-9 weeks were treated with the CSF1R inhibitor PLX3397 (40 mg/kg, p.o.

Neurochemical abnormalities in the hippocampus of male rats displaying audiogenic seizures, a genetic model of epilepsy.

Background: Epilepsy is a disorder characterized by recurrent seizures that affects 1% of the population. However, the neurochemical alterations observed in epilepsy are not fully understood. There are different animal models of epilepsy, such as genetic or drug induced.

Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain.

Background: Major depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects.

PI3K, mTOR and GSK3 modulate cytokines' production in peripheral leukocyte in temporal lobe epilepsy.

Introduction: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures.

Serotonin and dopamine receptors profile on peripheral immune cells from patients with temporal lobe epilepsy.

The role of inflammation and immune cells has been demonstrated in neurological diseases, including epilepsy. Leukocytes, as well as inflammatory mediators, contribute to abnormal processes that lead to a reduction in seizure threshold and synaptic reorganization. In this sense, identifying different phenotypes of circulating immune cells is essential to understanding the role of these cells in epilepsy.