Elaine Del-Bel

University of São Paulo-Ribeirão Preto School of Dentistry (FORP) · Basic and Oral Biology

Parkinson’s Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by u...

Background: Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson`s disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties. Objective: Evaluate the efficacy and safety of doxycycline in patients with PD and LID. Methods: This was an open-lab...

Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate mod...

Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clini...

Levo-dihydroxyphenylalanine (L-DOPA) therapy for Parkinson's disease (PD) patients improves motor symptoms, but long-term treatment induces side effects such as abnormal involuntary movements (levodopa-induced dyskinesia – LID). Increasing evidence has linked LID with neuroinflammatory reaction in the striatum involving microglia and astrocytes. Th...

L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia is a side effect of Parkinson's disease treatment and it is characterized by atypical involuntary movements. A link between neuroinflammation and L-DOPA-induced dyskinesia has been documented. Hydrogen gas (H2) has neuroprotective effects in Parkinson's disease models and has a major anti-inf...

Doxycycline (DOX) is a widely used antibiotic that is able to cross the blood-brain barrier. Several studies have shown its neuroprotective effect against neurodegeneration and have associated it with antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. We have recently demonstrated that DOX mimics nerve growth factor (NGF) signaling in P...

Several studies have reported that the tetracycline (TC) class antibiotic doxycycline (DOX) is effective against Parkinson’s disease (PD) pathomechanisms. The aim of the present work was three-fold: (i) Establish a model system to better characterize neuroprotection by DOX; (ii) Compare the rescue effect of DOX to that of other TC antibiotics; (iii...

Purpose: The majority of animal models of Parkinson’s disease (PD) focus on motor symptoms that are induced by unilateral injections of such neurotoxins as 6-hydroxydopamine (6-OHDA) in nigrostriatal dopaminergic pathways. However, motor changes that are induced by unilateral 6-OHDA injections may interfere with the identification of cognitive and...

The pharmacological manipulation of neuroinflammation appears to be a promising strategy to alleviate l-DOPA-induced dyskinesia (LID) in Parkinson’s disease (PD). Doxycycline (Doxy), a semisynthetic brain-penetrant tetracycline antibiotic having interesting anti-inflammatory properties, we addressed the possibility that this compound could resolve...

Schizophrenia is a complex and heterogeneous neurodevelopmental psychiatric disorder characterized by a variety of symptoms classically grouped into three main domains: positive (hallucinations, delusions, and thought disorder) and negative symptoms (social withdrawal, lack of affect) and cognitive dysfunction (attention, working and episodic memor...

Although issues surrounding diversity and inclusion in science are global, distinctive region-specific socioeconomic factors and operational biases interact to widen the opportunity gap and exacerbate the isolation of specific groups of disadvantaged scientists on the global stage. This commentary reviews the issues currently faced by the Latin Ame...

Rationale Autism spectrum disorder (ASD) is defined as a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction, restricted and repetitive patterns of behavior, and varying levels of intellectual disability. ASD is observed in early childhood and is one of the most severe chronic childhood disorde...

The majority of animal models of PD focus on the motor symptoms induced by unilateral injections of neurotoxins such as 6-hydroxidopamine (6-OHDA) in the nigrostriatal dopaminergic pathways. However, motor changes induced by unilateral 6-OHDA injections may interfere in the identification of cognitive and affective dysfunctions. To select an approp...

Background Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson’s disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties. Objective Evaluate the efficacy and safety of doxycycline in patients with PD and LID. Methods This was an open-labe...

Dysregulation of GABAergic neurotransmission has long been implicated in several psychiatric disorders, including schizophrenia, depression, and anxiety disorders. Alpha 5 subunit-containing GABAA receptors (α5-GABAAR), which are expressed mainly by pyramidal neurons in the hippocampus, have been proposed as a potential target to treat these psychi...

Despite attenuating the positive symptoms, drugs currently used to treat schizophrenia frequently do not improve the negative symptoms and cognitive impairments. In addition, they show low tolerability, which has been associated with high rates of treatment discontinuation. Recent evidence suggests that the endocannabinoid system may be a target fo...

Levodopa-induced dyskinesia (LID) is a common complication of Parkinson’s disease (PD) therapy. Nitric oxide in the central nervous system may have a role in its pathophysiology. The present work investigates plasma and CSF levels of nitric oxide metabolites nitrite and nitrate in patients with PD, LID, and healthy control. We measured plasma and C...

The existence of few biomarkers and the lack of a better understanding of the pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) require new approaches, as the metabolomic analysis, for discoveries. We aimed to identify a metabolic profile associated with LID in patients with PD in an original cohort, and to confirm th...

Psychological stress and occlusal alterations are contributing etiologic factors for temporomandibular and muscular disorders in the orofacial area. The neural modulation recruited for this relationship, however, is not elucidated. The aim of this study was to investigate potential central mechanisms involved in the exodontia-induced occlusal insta...

We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker pro...

Dyskinesia or abnormal involuntary movement is an unfortunate consequence of long-term therapy with L-DOPA, a gold standard for the treatment of Parkinson’s disease (PD). L-DOPA-induced dyskinesia (LID) is affected by age of onset, duration and severity of PD, L-DOPA dose, as well as gender. The main treatment modality is reduction of L-DOPA dose....

The musculoskeletal orofacial pain is a complex symptom of Parkinson's disease (PD) resulting in stomatognathic system dysfunctions aggravated by the disease rigidity and postural instability. We tested the effect of cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, in PD-related myofascial pain. Wistar adult female and male...

Although monoaminergic-based antidepressant drugs are largely used to treat major depressive disorder (MDD), their mechanisms are still incompletely understood. Intracellular Ca2+ (iCa2+) and Calmodulin 1(CaM-1) homeostasis have been proposed to participate in the therapeutic effects of these compounds. We investigated whether intra-hippocampal inh...

Interferon-γ (IFN-γ) is a proinflammatory cytokine that activates glial cells. IFN-γ is increased in the plasma and brain of Parkinson’s disease patients, suggesting its potential role in the disease. We investigated whether the IFN-γ deficiency could interfere with nigrostriatal degeneration induced by the neurotoxin 6-hydroxydopamine, L-DOPA-indu...

Cannabidiol (CBD), a major non-psychotomimetic component of the Cannabis sativa plant, shows therapeutic potential in several psychiatric disorders, including schizophrenia. The molecular mechanisms underlying the antipsychotic-like effects of CBD are not fully understood. Schizophrenia and antipsychotic treatment can modulate DNA methylation in th...

Background and purpose: L-DOPA-induced dyskinesia (LID) is a debilitating effect of treating Parkinson's disease with this drug. New therapeutic approaches that prevent or attenuate this side effect is needed. Experimental approach: Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesion were treat...

Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We foun...

Doxycycline has been used as antibiotic since the 1960s. Recently, studies have shown that doxycycline is neuroprotective in models of neurodegenerative diseases and brain injuries, mainly due to anti-inflammatory and anti-apoptotic effects. However, it is not known if doxycycline has neurotrophic potential, which is relevant, considering the role...

To evaluate the endocannabinoid system in an animal model of Parkinson's disease, in-tube solid-phase microextraction (in-tube SPME) was directly coupled to a tandem mass spectrometry (MS/MS) system for determination of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat brain samples. In-tube SPME—which consisted of a mi...

Our present objective was to better characterize the mechanisms that regulate striatal neuroinflammation in mice developing L-DOPA-induced dyskinesia (LID). For that, we used 6-hydroxydopamine (6-OHDA)-lesioned mice rendered dyskinetic by repeated intraperitoneal injections of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) and quantified ensuing neuroinfla...

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which...

The pyridobenzoxazepine compound, 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13), has been developed as a potential antipsychotic drug. We tested the hypothesis that JL13 is efficacious in both dopaminergic and glutamatergic animal models of schizophrenia. We investigated JL13 for its efficacy to prevent cocaine- and ket...

Schizophrenia patients show very complex symptoms in several psychopathological domains. Some of these symptoms remain poorly treated. Therefore, continued effort is needed to find novel pharmacological strategies for improving schizophrenia symptoms. Recently, minocycline, a second-generation tetracycline, has been suggested as an adjunctive treat...

Abstract Parkinson's disease (PD) is a neurodegenerative disorder for which only symptomatic treatments are available. Repurposing drugs that target α-synuclein aggregation, considered one of the main drivers of PD progression, could accelerate the development of disease-modifying therapies. In this work, we focused on chemically modified tetracycl...

Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We foun...

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which...

Although sex differences in memory tasks dependent on hippocampal function have been described in several species, including rodents and humans, the exact mechanisms involved remain debatable. The function of the small-conductance Ca2+-activated K+ channel type 3 has been associated with cognitive deficits, and its overexpression in male mice (T/T)...

Introduction Levodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and nitric oxide has a role on its pathophysiology. The present work aims to investigate CSF levels of nitric oxide metabolites nitrite and nitrate (NOx) in patients with PD and LID. Methods We measured CSF NOx levels in patients with PD with an...

Psychological stress and occlusal alteration are important etiologic factors for temporomandibular/masticatory muscular disorders. In particular, the exact physiologic mechanism underlying the relation by occlusal alteration and temporomandibular disorders remains unclear. Our purpose was to test the hypothesis that benzodiazepine therapy is able t...

Evidence suggests that physical exercise has effects on neuronal plasticity as well as overall brain health. This effect has been linked to exercise capacity in modulating the antioxidant status, when the oxidative stress is usually linked to the neuronal damage. Although high-intensity interval training (HIIT) is the training-trend worldwide, its...

Parkinson’s disease (PD) and l-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient’s quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating l-DOPA is no longer recommended as LID development is a funct...

Parkinson's disease (PD) has become a significant concern for public health due to its disabling nature and high prevalence in the aging population. No cure or disease-modifying drug exists besides the availability of symptomatic medical and surgical treatments, which has led to increased medical costs. To fill this gap, novel therapeutic approache...

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in diff...

We used mouse microglial cells in culture activated by lipopolysaccharide (LPS, 10 ng/ml) to study the anti-inflammatory potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis. Under LPS stimulation, CBD (1-10 μM) potently inhibited the release of prototypical proinflammatory cytokines (TNF-α and IL-1β) and that of glutamat...

Objective To evaluate the effects of photodynamic therapy (PDT) on the dura mater using the photosensitizers aluminum chloride phthalocyanine and methylene blue in in vivo assays. Methods Fifty-six male Wistar rats were divided into two groups; one submitted to PDT and the other submitted to the photosensitizers without their photoactivation (contr...

: Aggregated forms of the synaptic protein α-synuclein (αS) have been proposed to operate as a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´s disease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinant human αS to assess the anti-inflammatory and neuroprotective ac...

Objective: Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable...

Nitric oxide (NO) has chemical properties that make it uniquely suitable as an intracellular and intercellular messenger. NO is produced by the activity of the enzyme nitric oxide synthases (NOS). There is substantial and mounting evidence that slight abnormalities of NO may underlie a wide range of neurodegenerative disorders. NO participates of t...

Neurodegenerative diseases (NDs) are a group of chronic, progressive disorders characterized by the gradual loss of neurons that affect specific regions of the brain, which leads to deficits in specific functions (e.g., memory, movement, cognition). The mechanism that drives chronic progression of NDs remains elusive. Among the proposed underlying...

Depression is a mental illness with a complex and multifactorial etiology, which has been associated with stress and inflammation. Infections, autoimmune diseases, envenomation, and trauma induce an inflammatory response that is characterized by increasing levels of circulating cytokines (e.g., IL-1β) and lipid mediators [e.g., PGE2 and leukotriene...

Citrus fragrances have been used in aromatherapy for the treatment of anxiety, and the essential oil of Citrus sinensis (sweet orange) has shown promising results, although its mechanism of action was not known. The objective of this study was to evaluate the involvement of nitric oxide (NO) neurotransmission in the anxiolytic‐like effect of C. sin...

When activated, microglial cells have the potential not only to secrete typical proinflammatory mediators but also to release the neurotransmitter glutamate in amounts that may promote excitotoxicity. Here, we wished to determine the potential of the Parkinson's disease (PD) protein α‐Synuclein (αS) to stimulate glutamate release using cultures of...

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson’s disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, l-DOPA (l-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there...

The prevalence of Parkinson’s disease, which affects millions of people worldwide, is increasing due to the aging population. In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson’s disease encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkins...

Parkinson’s disease (PD) is a highly complex brain disorder regarding clinical presentation, pathogenesis, and therapeutics. The cardinal motor signs, i.e., rigidity, bradykinesia, and unilateral tremors, arise in consequence of a progressive neuron death during the prodromal phase. Although multiple transmission systems are involved in disease neu...

The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms. Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis...

Background and purpose: The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) bind to CB1 and CB2 receptors in the brain and modulate the mesolimbic dopaminergic pathway. This neurocircuitry is engaged by psychostimulant drugs, including cocaine. Although it is known that CB1 antagonism as well as CB2 activation inhibit certain effects...

The nitric oxide (NO) system has been proven to be a valuable modulator of L‐DOPA‐induced dyskinesia in parkinsonian rodents. NO activates the enzyme soluble guanylyl cyclase and elicits the synthesis of the second messenger cGMP. Although we have previously described the anti‐dyskinetic potential of NO synthase inhibitors on L‐DOPA‐induced dyskine...

The monoamine stabilizer (3S)-3-[3-(methenesulfonyl)phenyl]-1-propylpiperidine hidrochloride [(−)-OSU6162] is a promising compound for the treatment of neurological and psychiatric disorders, such as schizophrenia. Here, we tested the hypothesis that (−)-OSU6162 prevents hyperlocomotion and sensorimotor deficits in prepulse inhibition of the startl...