Background: Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce 'research waste', improve the effectiveness of pain research and therapy and promote the uptake of research evidence.
View Article and Find Full Text PDFRepeated administration of ketamine (KET) has been used to model schizophrenia-like symptomatology in rodents, but the psychotomimetic neurobiological and neuroanatomical underpinnings remain elusive. In parallel, the unmet need for a better treatment of schizophrenia requires the development of novel therapeutic strategies. Cannabidiol (CBD), a major non-addictive phytocannabinoid has been linked to antipsychotic effects with unclear mechanistic basis.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
April 2024
Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations.
View Article and Find Full Text PDFChronic stress and elevated levels of glucocorticoids (GCs), the main stress hormones, accelerate Alzheimer's disease (AD) onset and progression. A major driver of AD progression is the spreading of pathogenic Tau protein between brain regions, precipitated by neuronal Tau secretion. While stress and high GC levels are known to induce intraneuronal Tau pathology (i.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2024
Neuropsychiatric disorders, which are associated with stress hormone dysregulation, occur at different rates in men and women. Moreover, nowadays, preclinical and clinical evidence demonstrates that sex and gender can lead to differences in stress responses that predispose males and females to different expressions of similar pathologies. In this curated review, we focus on what is known about sex differences in classic mechanisms of stress response, such as glucocorticoid hormones and corticotrophin-releasing factor (CRF), which are components of the hypothalamicpituitary- adrenal (HPA) axis.
View Article and Find Full Text PDFChronic stress and high levels of the main stress hormones, and glucocorticoids (GC), are implicated in susceptibility to brain pathologies such as depression and Alzheimer's disease (AD), as they promote neural plasticity damage and glial reactivity, which can lead to dendritic/synaptic loss, reduced neurogenesis, mood deficits, and impaired cognition. Moreover, depression is implicated in the development of AD with chronic stress being a potential link between both disorders via common neurobiological underpinnings. Hereby, we summarize and discuss the clinical and preclinical evidence related to the detrimental effect of chronic stress as a precipitator of AD through the activation of pathological mechanisms leading to the accumulation of amyloid β (Aβ) and Tau protein.
View Article and Find Full Text PDFChronic stress and elevated levels of glucocorticoids (GCs), the main stress hormones, accelerate Alzheimer's disease (AD) onset and progression. A major driver of AD progression is the spreading of pathogenic Tau protein between brain regions, precipitated by neuronal Tau secretion. While stress and high GC levels are known to induce intraneuronal Tau pathology (.
View Article and Find Full Text PDFChronic stress and elevated levels of glucocorticoids (GCs), the main stress hormones, accelerate Alzheimer's disease (AD) onset and progression. A major driver of AD progression is the spreading of pathogenic Tau protein between brain regions, precipitated by neuronal Tau secretion. While stress and high GC levels are known to induce intraneuronal Tau pathology ( hyperphosphorylation, oligomerization) in animal models, their role in trans-neuronal Tau spreading is unexplored.
View Article and Find Full Text PDFBackground: Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, as well as diverse individual clinical profile, often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance.
View Article and Find Full Text PDFIntroduction: Given the ineffectiveness of the available drug treatment against Alzheimer disease (AD), light-based therapeutic modalities have been increasingly receiving attention with photobiomodulation (PBM) and, more recently, visual stimulation (VS) being among the most promising approaches. However, the PBM and VS light parameters tested so far, as well as their outcomes, vary a lot with conflicting results being reported.
Methods: Based on Scopus, PubMed, and Web of Science databases search, this systematic review summarizes, compares, and discusses 43 cell, animal, and human studies of PBM and VS related to cognitive decline and AD pathology.
Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain.
View Article and Find Full Text PDFExtracellular vesicles (EVs), secreted membranous nano-sized particles, are critical intercellular messengers participating in nervous system homeostasis, while recent evidence implicates EVs in Alzheimer's disease (AD) pathogenesis. Specifically, small EVs have been shown to spread toxic proteins, induce neuronal loss, and contribute to neuroinflammation and AD progression. On the other hand, EVs can reduce amyloid-beta deposition and transfer neuroprotective substances between cells, mitigating disease mechanisms.
View Article and Find Full Text PDFThe existence of a clear association between stress and cancer is still a matter of debate. Recent studies suggest that chronic stress is associated with some cancer types and may influence tumor initiation and patient prognosis, but its role in brain tumors is not known. Glioblastoma (GBM) is a highly malignant primary brain cancer, for which effective treatments do not exist.
View Article and Find Full Text PDFObjectives: The action of stress hormones, mainly glucocorticoids, starts and coordinates the systemic response to stressful events. The HPA axis activity is predicated on information processing and modulation by upstream centres, such as the hippocampus where adult-born neurons (hABN) have been reported to be an important component in the processing and integration of new information. Still, it remains unclear whether and how hABN regulates HPA axis activity and CORT production, particularly when considering sex differences.
View Article and Find Full Text PDFChronic stress and elevated glucocorticoids (GCs), the major stress hormones, are risk factors for Alzheimer's disease (AD) and promote AD pathomechanisms, including overproduction of toxic amyloid-β (Aβ) peptides and intraneuronal accumulation of hyperphosphorylated Tau protein. The latter is linked to downregulation of the small GTPase Rab35, which mediates Tau degradation via the endolysosomal pathway. Whether Rab35 is also involved in Aβ overproduction remains an open question.
View Article and Find Full Text PDFLike other members of the superfamily of nuclear receptors, the peroxisome proliferator-activated receptor γ (PPARγ), is a ligand-activated transcription factor known for its insulin-sensitizing actions in the periphery. Despite only sparse evidence for PPARγ in the CNS, many reports suggest direct PPARγ-mediated actions in the brain. This study aimed to (i) map PPARγ expression in rodent brain areas, involved in the regulation of cognitive, motivational, and emotional functions, (ii) examine the regulation of central PPARγ by physiological variables (age, sex, obesity); (iii) chemotypically identify PPARγ-expressing cells in the frontal cortex (FC) and hippocampus (HP); (iv) study whether activation of PPARγ by pioglitazone (Pio) in FC and HP cells can induce target gene expression; and (v) demonstrate the impact of activated PPARγ on learning behavior and motivation.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most common cause of dementia, affecting approximately 40 million people worldwide. The ineffectiveness of the available pharmacological treatments against AD has fostered researchers to focus on alternative strategies to overcome this challenge. Mechanical vibrations delivered in different stimulation modes have been associated with marked improvements in cognitive and physical performance in both demented and non-demented elderly.
View Article and Find Full Text PDFHistorically, many investigations into neurodegenerative diseases have focused on alterations in specific neuronal populations such as, for example, the loss of midbrain dopaminergic neurons in Parkinson's disease (PD) and loss of cholinergic transmission in Alzheimer's disease (AD). However, it has become increasingly clear that mammalian brain activities, from executive and motor functioning to memory and emotional responses, are strictly regulated by the integrity of multiple interdependent neuronal circuits. Among subcortical structures, the dopaminergic nigrostriatal and mesolimbic pathways as well as cholinergic innervation from basal forebrain and brainstem, play pivotal roles in orchestrating cognitive and non-cognitive symptoms in PD and AD.
View Article and Find Full Text PDFObjectives: The area of the subventricular zone (SVZ) in the adult brain exhibits the highest number of proliferative cells, which, together with the olfactory bulb (OB), maintains constant brain plasticity through the generation, migration and integration of newly born neurons. Despite Tau and its malfunction is increasingly related to deficits of adult hippocampal neurogenesis and brain plasticity under pathological conditions [e.g.
View Article and Find Full Text PDFThe hippocampus-prefrontal cortex circuit plays a major role in stress and in the neurobiology of depression and its treatment. Disruption of this circuit by lesioning the thalamic nucleus reuniens (RE) has been shown to prevent the detrimental effects of chronic mild stress on prefrontal cortex neuroplasticity indices in male rats. However, it remains unknown whether hippocampal neurostructural response to stress is modified by RE lesion.
View Article and Find Full Text PDFChronic pain manifests in multiple disorders and is highly debilitating. While its pathophysiology is not fully understood, the involvement of the mesocorticolimbic monoaminergic systems have been shown to play a critical role in chronic pain emergence and/or maintenance. In this study, we analyzed the levels of monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in mesocorticolimbic areas - medial prefrontal cortex, orbitofrontal cortex, striatum, nucleus accumbens and amygdala - 1 month after a neuropathic lesion, Spared Nerve Injury (SNI).
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