TopicNeuroscience

BDNF

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45Total items

40ePosters

5Seminars

Latest

SeminarNeuroscience

Pharmacological exploitation of neurotrophins and their receptors to develop novel therapeutic approaches against neurodegenerative diseases and brain trauma

Ioannis Charalampopoulos

Professor of Pharmacology, Medical School, University of Crete & Affiliated Researcher, Institute of Molecular Biology & Biotechnology (IMBB), Foundation for Research and Technology Hellas (FORTH)

Mar 7, 2025

Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic compounds which selectively resemble neurotrophins’ effects, presenting preferable pharmacological properties and promoting neuroprotection and repair against neurodegeneration. In addition, the combination of these molecules with 3D cultured human neuronal cells, and their targeted delivery in the brain ventricles through soft robotic systems, could offer novel therapeutic approaches against neurodegenerative diseases and brain trauma.

SeminarNeuroscience

Neuron-glial interactions in health and disease: from cognition to cancer

Michelle Monje

Stanford Medicine

Mar 14, 2023

In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Activity-dependent proliferation of healthy glial progenitors, oligodendrocyte precursor cells (OPCs), and the consequent generation of new oligodendrocytes contributes to adaptive myelination. This plasticity of myelin tunes neural circuit function and contributes to healthy cognition. The robust mitogenic effect of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, suggests that dysregulated or “hijacked” mechanisms of myelin plasticity might similarly promote malignant cell proliferation in this devastating group of brain cancers. Indeed, neuronal activity promotes progression of both high-grade and low-grade glioma subtypes in preclinical models. Crucial mechanisms mediating activity-regulated glioma growth include paracrine secretion of BDNF and the synaptic protein neuroligin-3 (NLGN3). NLGN3 induces multiple oncogenic signaling pathways in the cancer cell, and also promotes glutamatergic synapse formation between neurons and glioma cells. Glioma cells integrate into neural circuits synaptically through neuron-to-glioma synapses, and electrically through potassium-evoked currents that are amplified through gap-junctional coupling between tumor cells This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. Thus, neuron-glial interactions not only modulate neural circuit structure and function in the healthy brain, but paracrine and synaptic neuron-glioma interactions also play important roles in the pathogenesis of glial cancers. The mechanistic parallels between normal and malignant neuron-glial interactions underscores the extent to which mechanisms of neurodevelopment and plasticity are subverted by malignant gliomas, and the importance of understanding the neuroscience of cancer.

SeminarNeuroscience

Malignant synaptic plasticity in pediatric high-grade gliomas

Kathryn Taylor

Stanford

May 25, 2022

Pediatric high-grade gliomas (pHGG) are a devastating group of diseases that urgently require novel therapeutic options. We have previously demonstrated that pHGGs directly synapse onto neurons and the subsequent tumor cell depolarization, mediated by calcium-permeable AMPA channels, promotes their proliferation. The regulatory mechanisms governing these postsynaptic connections are unknown. Here, we investigated the role of BDNF-TrkB signaling in modulating the plasticity of the malignant synapse. BDNF ligand activation of its canonical receptor, TrkB (which is encoded for by the gene NTRK2), has been shown to be one important modulator of synaptic regulation in the normal setting. Electrophysiological recordings of glioma cell membrane properties, in response to acute neurotransmitter stimulation, demonstrate in an inward current resembling AMPA receptor (AMPAR) mediated excitatory neurotransmission. Extracellular BDNF increases the amplitude of this glutamate-induced tumor cell depolarization and this effect is abrogated in NTRK2 knockout glioma cells. Upon examining tumor cell excitability using in situ calcium imaging, we found that BDNF increases the intensity of glutamate-evoked calcium transients in GCaMP6s expressing glioma cells. Western blot analysis indicates the tumors AMPAR properties are altered downstream of BDNF induced TrkB activation in glioma. Cell membrane protein capture (via biotinylation) and live imaging of pH sensitive GFP-tagged AMPAR subunits demonstrate an increase of calcium permeable channels at the tumors postsynaptic membrane in response to BDNF. We find that BDNF-TrkB signaling promotes neuron-to-glioma synaptogenesis as measured by high-resolution confocal and electron microscopy in culture and tumor xenografts. Our analysis of published pHGG transcriptomic datasets, together with brain slice conditioned medium experiments in culture, indicates the tumor microenvironment as the chief source of BDNF ligand. Disruption of the BDNF-TrkB pathway in patient-derived orthotopic glioma xenograft models, both genetically and pharmacologically, results in an increased overall survival and reduced tumor proliferation rate. These findings suggest that gliomas leverage normal mechanisms of plasticity to modulate the excitatory channels involved in synaptic neurotransmission and they reveal the potential to target the regulatory components of glioma circuit dynamics as a therapeutic strategy for these lethal cancers.

SeminarNeuroscience

Neuronal plasticity and neurotrophin signaling as the common mechanism for antidepressant effect

Eero Castrén

Neuroscience Center, University of Helsinki, Finland

Mar 18, 2022

Neuronal plasticity has for a long time been considered important for the recovery from depression and for the antidepressant drug action, but how the drug action is translated to plasticity has remained unclear. Brain-derived neurotrophic factor (BDNF) and its receptor TRKB are critical regulators of neuronal plasticity and have been implicated in the antidepressant action. We have recently found that many, if not all, different antidepressants, including serotonin selective SSRIs, tricyclic as well as fast-acting ketamine, directly bind to TRKB, thereby promoting TRKB translocation to synaptic membranes, which increases BDNF signaling. We have previously shown that antidepressant treatment induces a juvenile-like state of activity in the cortex that facilitates beneficial rewiring of abnormal networks. We recently showed that activation of TRKB receptors in parvalbumin-containing interneurons orchestrates cortical activation states and is both necessary and sufficient for the antidepressantinduced cortical plasticity. Our findings open a new framework how the action of antidepressants act: rather than regulating brain monoamine concentrations, antidepressants directly bind to TRKB and allosterically promote BDNF signaling, thereby inducing a state of plasticity that allows re-wiring of abnormal networks for better functionality.

SeminarNeuroscience

How the immune system shapes synaptic functions

Michela Matteoli

Humanitas Research Hospital and CNR Institute of Neuroscience, Milano, Italy

Mar 16, 2021

The synapse is the core component of the nervous system and synapse formation is the critical step in the assembly of neuronal circuits. The assembly and maturation of synapses requires the contribution of secreted and membrane-associated proteins, with neuronal activity playing crucial roles in regulating synaptic strength, neuronal membrane properties, and neural circuit refinement. The molecular mechanisms of synapse assembly and refinement have been so far largely examined on a gene-by-gene basis and with a perspective fully centered on neuronal cells. However, in the last years, the involvement of non-neuronal cells has emerged. Among these, microglia, the resident immune cells of the central nervous system, have been shown to play a key role in synapse formation and elimination. Contacts of microglia with dendrites in the somatosensory cortex were found to induce filopodia and dendritic spines via Ca2+ and actin-dependent processes, while microglia-derived BDNF was shown to promote learning-dependent synapse formation. Microglia is also recognized to have a central role in the widespread elimination (or pruning) of exuberant synaptic connections during development. Clarifying the processes by which microglia control synapse homeostasis is essential to advance our current understanding of brain functions. Clear answers to these questions will have important implications for our understanding of brain diseases, as the fact that many psychiatric and neurological disorders are synaptopathies (i.e. diseases of the synapse) is now widely recognized. In the last years, my group has identified TREM2, an innate immune receptor with phagocytic and antiinflammatory properties expressed in brain exclusively by microglia, as essential for microglia-mediated synaptic refinement during the early stages of brain development. The talk will describe the role of TREM2 in synapse elimination and introduce the molecular actors involved. I will also describe additional pathways by which the immune system may affect the formation and homeostasis of synaptic contacts.

BDNF

Latest

Pharmacological exploitation of neurotrophins and their receptors to develop novel therapeutic approaches against neurodegenerative diseases and brain trauma

Neuron-glial interactions in health and disease: from cognition to cancer

Malignant synaptic plasticity in pediatric high-grade gliomas

Neuronal plasticity and neurotrophin signaling as the common mechanism for antidepressant effect

How the immune system shapes synaptic functions

FKBP51 REGULATES BDNF/TRKB SIGNALING AND STRESS-DRIVEN SYNAPTIC PLASTICITY

SSAO-MEDIATED DECREASE OF ENDOTHELIAL BDNF RELEASE AFFECTS NEURONAL GLUA1 AND PSD95 EXPRESSION: A PERIPHERAL MECHANISM INDUCING NVU AND CNS DISTURBANCES

CHONDROITINASE ABC AND BDNF MRNA POLYPLEX DELIVERY SUPPORTS NEURONAL REGENERATION IN ACUTE HIPPOCAMPAL LESIONS

ACTIVE BODY, IMPROVED BRAIN: EFFECTS OF EXERCISE INTERVENTIONS ON BDNF LEVELS ACROSS THE LIFESPAN - SYSTEMATIC-REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS WITH MODERATOR ANALYSES

CIRCULATING BDNF IS ASSOCIATED WITH ATTENUATED INFLAMMATION-RELATED NEUROAXONAL INJURY WHILE TAU-RELATED BIOMARKERS REMAIN ADDITIVE

PRECLINICAL VALIDATION OF A BDNF ALLOSTERIC MODULATOR IN A HUMAN STEM CELL-DERIVED NEURAL MODEL: IMPLICATIONS FOR HUNTINGTON'S DISEASE

BDNF/PROBDNF SIGNALING REGULATES MICROGLIAL PHENOTYPE AND INFLAMMATORY RESPONSES IN THE MOUSE HIPPOCAMPUS

THE ROLE OF MAGNETIC STIMULATION IN BDNF-TARGETED THERAPY FOR SUBACUTE STROKE

ALTERED BDNF AND TRKB LEVELS IN CEREBELLAR PURKINJE CELLS MAY CONTRIBUTE TO ATAXIA IN A CHRISTIANSON SYNDROME MOUSE MODEL

SMALL MOLECULES AS A PHARMACOLOGICAL STRATEGY TO PROTECT BDNF RECEPTOR IN ALZHEIMER’S DISEASE

BDNF RECEPTOR DYSREGULATION IN ALZHEIMER'S-DISEASE: EXTRACELLULAR VESICLE-MEDIATED TRANSPORT OF A SYNAPTOTOXIC TRKB FRAGMENT

MITOCHONDRIAL FISSION AS A KEY REGULATOR OF BDNF-MEDIATED SYNAPTIC REMODELING

SEX-SPECIFIC ROLE OF NEUROPLASTICITY FACTOR BDNF IN BEHAVIORAL, NEUROBIOLOGICAL, AND METABOLIC EFFECTS OF KETOGENIC DIET IN MICE

THE ROLE OF BDNF/PI3K/AKT/NRF2 SIGNALING IN NICOTINE’S PROTECTIVE EFFECTS AGAINST MPTP-INDUCED PARKINSON’S DISEASE

DIFFERENTIAL EFFECTS OF OUABAIN ON BDNF EXPRESSION IN LUNG AND BRAIN IN A MURINE MODEL OF MIXED ASTHMA

VEGF-A/VEGFR2 EXPRESSION IN RHO-P23H MICE: EFFECTS OF BDNF INTRAVITREAL INJECTIONS

SEX-SPECIFIC AND STAGE-DEPENDENT EPIGENETIC REGULATION OF BDNF IN BIPOLAR DISORDER: INTEGRATING TRANSCRIPTIONAL AND METHYLATION SIGNATURES

THE INFLUENCE OF MAGNESIUM IONS ON THE ELECTROPHYSIOLOGICAL, ANALGESIC, AND BDNF-INDUCED NEUROMODULATION OF MORPHINE EFFECTS IN DIABETIC RATS

NEUROBIOLOGICAL CONSEQUENCES OF CHRONIC SLEEP LOSS: HIPPOCAMPAL NEURONAL PLASTICITY AND BDNF SIGNALING

LONG-TERM CONSEQUENCES OF ADOLESCENT EXPOSURE TO JWH-018 IN MALE AND FEMALE WILD-TYPE AND BDNF VAL66MET MICE

THE BENEFICIAL EFFECTS OF VOLUNTARY RUNNING ON ADULT NEUROGENESIS DEPEND ON THE AVAILABILITY OF BDNF IN THE BRAIN

Role of BDNF, adenosine A2AR and cannabinoid receptors on postnatal oligodendrogenesis from SVZ-derived neural stem cell cultures

A role for the BDNF system in the activity-based anorexia rat model: focus on the amygdala

The S1PR2-CCL2-BDNF-TrkB pathway mediates neuroinflammation, alterations in GABAergic neurotransmission and motor incoordination in hyperammonemic rats

A far upstream enhancer is a crucial regulator of BDNF gene expression in rodent neurons and astrocytes

BDNF-induced synaptic plasticity: The role of mitochondrial fission

BDNF rescues absence seizures and their comorbid memory deficits

BDNF/TrkB signalling, in cooperation with muscarinic signalling, retrogradely regulates PKA pathway to phosphorylate SNAP-25 and Synapsin-1 at the NMJ

Cerebellar BDNF signaling downregulation and autistic-like traits: Insights from a cholesterol storage disorder mouse model

Effects of ketogenic diet and BDNF deficiency in mouse chronic restraint stress model

Effects of VEGF and BDNF administration on KCC2 levels in axotomized extraocular motoneurons

Fragile-X-messenger ribonucleoprotein mediates BDNF-induced upregulation of GluN2B-containing NMDA receptors: Role in LTP of CA1 synapses

Functional internally tagged Vps10p-domain receptors: A novel tool to investigate their endosomal itineraries, dimerization, and ligand interactions that reveals their potential role in BDNF transport

Interaction of BDNF and glucocorticoid signaling in shaping neuronal plasticity

Investigating central BDNF expression in an anorexia nervosa-like mouse model: Implications for diagnosis and prognosis

Loss of neuroprotection in Alzheimer’s disease: Shedding light on BDNF receptor cleavage and its mirroring in extracellular vesicles

The neurophysiological mechanisms of impaired manual dexterity in Parkinson's disease: A multimodal study using PET/CT, EEG, and BDNF

A potential new source of TrkB dysregulation: Microglia possess the machinery for BDNF receptor cleavage

Sex-dependent BDNF-mediated effects of Fingolimod on the architecture of mouse hippocampal neurons

Therapeutic potential of BDNF and neurosteroids DHEA and DHEAS in an in vitro model of Parkinson’s disease