Brain-derived neurotrophic factor modulation in response to oxidative stress and corticosterone: role of scopolamine and mirtazapine.

Unlabelled: Major Depressive Disorder (MDD) is a very complex disease, challenging to study and manage. The complexities of MDD require extensive research of its mechanisms to develop more effective therapeutic approaches. Crucial in the context of this disease is the role of brain-derived neurotrophic factor (BDNF) signaling pathway.

Spatiotemporal Dysregulation of Neuron-Glia Related Genes and Pro-/Anti-Inflammatory miRNAs in the Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD), the leading cause of dementia, is a multifactorial disease influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators of gene expression and play significant roles in AD onset and progression. This exploratory study analyzed the expression levels of 28 genes and 5 miRNAs (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, and miR-155-5p) related to AD pathology and neuroimmune responses using RT-qPCR.

Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hallmarks of Niemann-Pick type C disease but is not sufficient to halt neurodegeneration.

Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 could be a potential therapeutic target in Niemann-Pick type C (NPC) disease, a rare and fatal neurodegenerative disorder, characterized by cholesterol accumulation in endolysosomal compartments.

S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5.

Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD.

Controversies about the cardiovascular effects of OM3FA. Did inappropriate placebos skew clinical trial results?

Several observational studies suggest that greasy fish may reduce cardiovascular risk, whose benefits have been attributed to the presence Omega-3 polyunsaturated fatty acids (OM3FA). However, there are some randomized controlled trials (RCTs) that have shown contradictory results concerning the cardiovascular benefits of OM3FA. Analyzing these RCTs we found that the use of olive oil in some RCTs could be responsible for contradictory results, since both.

In vivo Bio-Distribution and Toxicity Evaluation of Polymeric and Lipid-Based Nanoparticles: A Potential Approach for Chronic Diseases Treatment.

Introduction: Nanoparticles (NPs), as drug delivery systems, appear to be a promising tool for prolonged therapeutic strategies as they allow a controlled drug release over time. However, most of the studies found in the literature simply contemplate the use of a single or low number of dosages with low NPs concentrations. In the context of chronic diseases, like Alzheimer's disease, cancer or human immunodeficiency virus (HIV), where the therapeutic scheme is also chronic, studies with numerous repeated dosages are often neglected.

Impairment of adenosinergic system in Rett syndrome: Novel therapeutic target to boost BDNF signalling.

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through AR it potentiates BDNF synaptic actions in healthy animals.

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer's Disease Pathophysiology.

Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer's disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.

Microglial Sirtuin 2 Shapes Long-Term Potentiation in Hippocampal Slices.

Microglial cells have emerged as crucial players in synaptic plasticity during development and adulthood, and also in neurodegenerative and neuroinflammatory conditions. Here we found that decreased levels of Sirtuin 2 (Sirt2) deacetylase in microglia affects hippocampal synaptic plasticity under inflammatory conditions. The results show that long-term potentiation (LTP) magnitude recorded from hippocampal slices of wild type mice does not differ between those exposed to lipopolysaccharide (LPS), a pro-inflammatory stimulus, or BSA.

From Cannabinoids and Neurosteroids to Statins and the Ketogenic Diet: New Therapeutic Avenues in Rett Syndrome?

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused mainly by mutations in the gene, being one of the leading causes of mental disability in females. Mutations in the gene are responsible for 95% of the diagnosed RTT cases and the mechanisms through which these mutations relate with symptomatology are still elusive. Children with RTT present a period of apparent normal development followed by a rapid regression in speech and behavior and a progressive deterioration of motor abilities.

Enhanced LTP in aged rats: Detrimental or compensatory?

Age-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and hippocampal LTP was evaluated.

Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.

Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected.

Adenosine A2A receptor activation is determinant for BDNF actions upon GABA and glutamate release from rat hippocampal synaptosomes.

Adenosine, through A(2A) receptor (A(2A)R) activation, can act as a metamodulator, controlling the actions of other modulators, as brain-derived neurotrophic factor (BDNF). Most of the metamodulatory actions of adenosine in the hippocampus have been evaluated in excitatory synapses. However, adenosine and BDNF can also influence GABAergic transmission.

Brain-derived neurotrophic factor mediates neuroprotection against Aβ-induced toxicity through a mechanism independent on adenosine 2A receptor activation.

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival through TrkB-FL activation. The activation of adenosine A2A receptors (A2AR) is essential for most of BDNF-mediated synaptic actions, such as synaptic plasticity, transmission and neurotransmitter release. We now aimed at evaluating the A2AR influence upon BDNF-mediated neuroprotection against Aβ25-35 toxicity in cultured neurons.

Dysregulation of TrkB Receptors and BDNF Function by Amyloid-β Peptide is Mediated by Calpain.

Brain-derived neurotrophic factor (BDNF) and its high-affinity full-length (FL) receptor, TrkB-FL, play a central role in the nervous system by providing trophic support to neurons and regulating synaptic plasticity and memory. TrkB and BDNF signaling are impaired in Alzheimer's disease (AD), a neurodegenerative disease involving accumulation of amyloid-β (Aβ) peptide. We recently showed that Aβ leads to a decrease of TrkB-FL receptor and to an increase of truncated TrkB receptors by an unknown mechanism.

Impact of in vivo chronic blockade of adenosine A2A receptors on the BDNF-mediated facilitation of LTP.

Brain-derived neurotrophic factor (BDNF) through the activation of its receptor (TrkB-FL) exert well-described neuroprotective effects playing a major role in hippocampal synaptic transmission and plasticity such as long-term potentiation (LTP), a molecular surrogate for learning and memory. Impairments in BDNF signalling have been associated to several neurodegenerative disorders such as Alzheimer's disease (AD). Therefore, the reestablishment of BDNF actions is considered a promising strategy for AD treatment.

Challenges and promises in the development of neurotrophic factor-based therapies for Parkinson's disease.

Parkinson's disease (PD) is a chronic movement disorder typically coupled to progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The treatments currently available are satisfactory for symptomatic management, but the efficacy tends to decrease as neuronal loss progresses. Neurotrophic factors (NTFs) are endogenous proteins known to promote neuronal survival, even in degenerating states.

Adenosine A(2A) Receptors as novel upstream regulators of BDNF-mediated attenuation of hippocampal Long-Term Depression (LTD).

Hippocampal Long-Term Potentiation (LTP) is facilitated by BDNF, through the activation of tropomyosin-related kinase B (TrkB) receptors. However, an influence of BDNF upon Long-Term Depression (LTD) was also shown. The present work aimed to further evaluate the effect of BDNF and TrkB receptors upon CA1 hippocampal LTD and to elucidate whether this effect is under the upstream control of other signalling processes, such as the adenosine A(2A)Receptors (A(2A)Rs).

Neuroprotection afforded by adenosine A2A receptor blockade is modulated by corticotrophin-releasing factor (CRF) in glutamate injured cortical neurons.

In situations of hypoxia, glutamate excitotoxicity induces neuronal death. The release of extracellular adenosine is also triggered and is accompanied by an increase of the stress mediator, corticotrophin-releasing factor (CRF). Adenosine A(2A) receptors contribute to glutamate excitoxicity and their blockade is effective in stress-induced neuronal deficits, but the involvement of CRF on this effect was never explored.

Extracellular alpha-synuclein oligomers modulate synaptic transmission and impair LTP via NMDA-receptor activation.

Parkinson's disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of α-synuclein (a-syn) in various brain regions is the major pathological hallmark. Indeed, the motor symptoms in PD are caused by a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In addition to the well known motor dysfunction in PD patients, cognitive deficits and memory impairment are also an important part of the disorder, probably due to disruption of synaptic transmission and plasticity in extrastriatal areas, including the hippocampus.