Comparative analysis of uninduced and neuronally-induced human dental pulp stromal cells in a 6-OHDA model of Parkinson's disease.

Background: In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA).

Macro and micro-sleep dysfunctions as translational biomarkers for Parkinson's disease.

Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the links between sleep dysfunctions in PD, focusing most closely on those data from animal and mathematical/computational models, as well as in human-based studies that explore the electrophysiological and molecular mechanisms by which PD and sleep may be intertwined, whether as predictors or consequences of the disease. It is possible to clearly state that leucine-rich repeat kinase 2 gene (LRRK2) is significantly related to alterations in sleep architecture, particularly affecting rapid eye movement (REM) sleep and non-REM sleep, thus impacting sleep quality.

Electrophysiological damage to neuronal membrane alters ephaptic entrainment.

The brain is commonly understood as a complex network system with a particular organization and topology that can result in specific electrophysiological patterns. Among all the dynamic elements resulting from the circuits of the brain's network, ephapticity is a cellular communication mechanism that has received little attention. To understand the network's properties of ephaptic entrainment, we start investigating the ephaptic effect on a single neuron.

Metabolic dysfunctions in the intranigral rotenone model of Parkinson's disease.

Parkinson disease (PD) is a chronic neurodegenerative disorder characterized by a progressive loss of dopamine neurons in the substantia nigra pars compacta (SNpc). In the last years, a growing interest to study the relationship between metabolic dysfunction and neurodegenerative disease like PD has emerged. This study aimed to evaluate the occurrence of possible changes in metabolic homeostasis due to intranigral rotenone administration, a neurotoxin that damages dopaminergic neurons leading to motor impairments mimicking those that happen in PD.

Folic Acid and Vitamin B12 Prevent Deleterious Effects of Rotenone on Object Novelty Recognition Memory and Expression in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra of rats using the neurotoxin rotenone.

STAT-3 signaling role in an experimental model of nephropathy induced by doxorubicin.

The focal segmental glomerulosclerosis (FSGS) is one of the most frequent glomerulopathy in the world, being considered a significative public health problem worldwide. The disease is characterized by glomerular loss mainly due to inflammation process and collagen fibers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation and in renal cells it has been related with fibrosis, acting on the progression of the lesion.

Olfaction and Melatonin: The Use of the Olfactory Discrimination Test.

In order to investigate the role of melatonin in olfactory function, we present the olfactory discrimination test as a simple and low-cost behavioral assessment. The test consists in evaluating the time that each rat spent in two compartments: one has a familiar odor (sawdust with the smell from the animal) and the other one with an unfamiliar odor (clean sawdust). Animals with the normal olfactory functions will discriminate between these two odors and will spend more time in the familiar compartment.

MT melatonin receptors expressed in the olfactory bulb modulate depressive-like behavior and olfaction in the 6-OHDA model of Parkinson's disease.

Melatonin MT and MT receptors are expressed in the glomerular layer of the olfactory bulb (OB); however, the role of these receptors has not been evaluated until now. Considering the association of the OB with olfactory and depressive disorders in Parkinson's disease (PD), we sought to investigate the involvement of melatonin receptors in these non-motor disturbances in an intranigral 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. We demonstrate the presence of functional melatonin receptors in dopaminergic neurons of the glomerular layer.

Disruption of neocortical synchronisation during slow-wave sleep in the rotenone model of Parkinson's disease.

Parkinson's disease motor dysfunctions are associated with improperly organised neural oscillatory activity. The presence of such disruption at the early stages of the disease in which altered sleep is one of the main features could be a relevant predictive feature. Based on this, we aimed to investigate the neocortical synchronisation dynamics during slow-wave sleep (SWS) in the rotenone model of Parkinson's disease.

Potential new therapies against a toxic relationship: neuroinflammation and Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder classically associated with motor symptoms, but several nonmotor disturbances appear decades before the clinical diagnosis of the disease. A variety of hypotheses exist to explain the onset of PD, and neuroinflammation is one of the most investigated processes. In fact, strong evidence suggests that PD begins with an inflammatory process; currently, however, no anti-inflammatory therapy is clinically employed to alleviate the typical motor and the prodromal disturbances such as olfactory loss, cognitive impairments, depression and anxiety, sleep disturbances, and autonomic disorders.

Electrocortical high frequency activity and respiratory entrainment in 6-hydroxydopamine model of Parkinson's disease.

Parkinson's disease is characterized by motor symptoms (akinesia, rigidity, etc.), which are associated with the degeneration of the dopaminergic neurons of the midbrain. In addition, olfactory impairment that usually develops before the detection of motor deficits, is detected in 90% of Parkinsonian patients.

Increased Mmp/Reck Expression Ratio Is Associated with Increased Recognition Memory Performance in a Parkinson's Disease Animal Model.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Among its non-motor symptoms, sleep disorders are extremely common, being linked to cognitive and memory disruption. The microenvironment, particularly the extracellular matrix (ECM), is deeply involved in memory consolidation as well as in neuropathological processes, such as inflammation, damage to the blood-brain barrier and neuronal death.

Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition.

Olfaction in female Wistar rats is influenced by dopaminergic periglomerular neurons after nigral and bulbar lesions.

Hyposmia is found in Parkinsonian patients decades before the onset of motor disorders. The same occurs with sleep disorders, especially infuencing rapid eye movement (REM) sleep, which affect a large percentage of people who have Parkinson's disease. These two disturbances presumably are closely related to a dopaminergic dysfunction.

Chronic sleep restriction increases pain sensitivity over time in a periaqueductal gray and nucleus accumbens dependent manner.

Painful conditions and sleep disturbances are major public health problems worldwide and one directly affects the other. Sleep loss increases pain prevalence and severity; while pain disturbs sleep. However, the underlying mechanisms are largely unknown.

Dopaminergic Lesion in the Olfactory Bulb Restores Olfaction and Induces Depressive-Like Behaviors in a 6-OHDA Model of Parkinson's Disease.

Olfactory impairments and depressive behavior are commonly reported by individuals with Parkinson's disease (PD) being observed before motor symptoms. The mechanisms underlying these clinical manifestations are not fully elucidated. However, the imbalance in dopaminergic neurotransmission seems to play an important role in this context.

REM sleep deprivation and dopaminergic D2 receptors modulation increase recognition memory in an animal model of Parkinson's disease.

Cognitive impairment is an important non-motor symptom of Parkinson's disease (PD). The neuronal death in nigrostriatal pathway is the main factor for motor symptoms and recent studies indicate a possible influence in non-motor symptoms as well. The pedunculopontine tegmental nucleus (PPT) and basal ganglia are closely related anatomically and functionally and, since they are affected by neurodegeneration in PD, they might be involved in recognition memory.

Dopaminergic mechanisms in periaqueductal gray-mediated antinociception.

As important as perceiving pain is the ability to modulate this perception in some contextual salient situations. The periaqueductal gray (PAG) is perhaps the most important site of endogenous pain modulation; however, little is known about dopaminergic mechanisms underlying PAG-mediated antinociception. In this study, we used a pharmacological approach to evaluate this subject.

Olfactory impairment is related to REM sleep deprivation in rotenone model of Parkinson's disease.

Introduction: Olfactory dysfunction affects about 85-90% of Parkinson's disease (PD) patients with severe deterioration in the ability of discriminate several types of odors. In addition, studies reported declines in olfactory performances during a short period of sleep deprivation. Besides, PD is also known to strongly affect the occurrence and maintenance of rapid eye movement (REM) sleep.

Cholinergic Oculomotor Nucleus Activity Is Induced by REM Sleep Deprivation Negatively Impacting on Cognition.

Several efforts have been made to understand the involvement of rapid eye movement (REM) sleep for cognitive processes. Consolidation or retention of recognition memories is severely disrupted by REM sleep deprivation (REMSD). In this regard, pedunculopontine tegmental nucleus (PPT) and other brainstem nuclei, such as pontine nucleus (Pn) and oculomotor nucleus (OCM), appear to be candidates to take part in this REM sleep circuitry with potential involvement in cognition.

REM sleep deprivation promotes a dopaminergic influence in the striatal MT2 anxiolytic-like effects.

The aim of this study was to investigate the possible anxiolytic-like effects of striatal MT2 activation, and its counteraction induced by the selective blockade of this receptor. Furthermore, we analyzed this condition under the paradigm of rapid eye movement (REM) sleep deprivation (REMSD) and the animal model of Parkinson's disease (PD) induced by rotenone. Male Wistar rats were infused with intranigral rotenone (12 μg/μL), and 7 days later were subjected to 24 h of REMSD.

Unraveling a new circuitry for sleep regulation in Parkinson's disease.

Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation.