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A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic ...

Fonseca-Gomes, João; Costa-Coelho, Tiago; Ferreira-Manso, Mafalda; Inteiro-Oliveira, Sara; Vaz, Sandra H.; Alemãn-Serrano, Nuno

In Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology seve...


TrkC Intracellular Signalling in the Brain Fear Network During the Formation of...

Silva, Francisca; Masella, Gianluca; Madeira, Maria Francisca; Duarte, Carlos B.; Santos, Mónica

Learned fear is orchestrated by a brain fear network that comprises the amygdala, hippocampus and the medial prefrontal cortex. Synaptic plasticity within this network is critical for the formation of proper fear memories. Known for their role in the promotion of synaptic plasticity, neurotrophins position as obvious candidates in the regulation of fear processes. Indeed, recent evidence from our laboratory and...


Mitochondria as central hubs in synaptic modulation

Duarte, Filipe V.; Ciampi, Daniele; Duarte, Carlos B.

Mitochondria are present in the pre- and post-synaptic regions, providing the energy required for the activity of these very specialized neuronal compartments. Biogenesis of synaptic mitochondria takes place in the cell body, and these organelles are then transported to the synapse by motor proteins that carry their cargo along microtubule tracks. The transport of mitochondria along neurites is a highly regulat...


Biomarkers of hypoxic-ischemic encephalopathy: a systematic review

Caramelo, Inês; Coelho, Margarida; Rosado, Miguel; Cardoso, Carla M P; Dinis, Alexandra; Duarte, Carlos B.; Grãos, Mário; Manadas, Bruno

Background Current diagnostic criteria for hypoxic–ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610). Data sources Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English origin...


Posttranslational modifications of proteins are key features in the identificat...

Salazar, Ivan L.; Lourenço, Ana S. T.; Manadas, Bruno; Baldeiras, Inês; Ferreira, Cláudia; Teixeira, Anabela Claro; Mendes, Vera M.; Novo, Ana Margarida

Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system (CNS) characterized by demyelination and concomitant axonal loss. The lack of a single specific test, and the similarity to other inflammatory diseases of the central nervous system, makes it difficult to have a clear diagnosis of multiple sclerosis. Therefore, laboratory tests that allows a clear and definite diagnosis...


Transient incubation of cultured hippocampal neurons in the absence of magnesiu...

Mele, Miranda; Vieira, Ricardo; Correia, Bárbara; Luca, Pasqualino De; Duarte, Filipe V.; Pinheiro, Paulo S.; Duarte, Carlos B.

Cell culture models are important tools to study epileptogenesis mechanisms. The aim of this work was to characterize the spontaneous and synchronized rhythmic activity developed by cultured hippocampal neurons after transient incubation in zero Mg2+ to model Status Epilepticus. Cultured hippocampal neurons were transiently incubated with a Mg2+-free solution and the activity of neuronal networks was evaluated ...


Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Dis...

Mele, Miranda; Costa, Rui O.; Duarte, Carlos B.

GABAA receptors (GABAAR) are the major players in fast inhibitory neurotransmission in the central nervous system (CNS). Regulation of GABAAR trafficking and the control of their surface expression play important roles in the modulation of the strength of synaptic inhibition. Different pieces of evidence show that alterations in the surface distribution of GABAAR and dysregulation of their turnover impair the a...


BDNF-Live-Exon-Visualization (BLEV) Allows Differential Detection of BDNF Trans...

Singer, Wibke; Manthey, Marie; Panford-Walsh, Rama; Matt, Lucas; Geisler, Hyun-Soon; Passeri, Eleonora; Baj, Gabriele; Tongiorgi, Enrico; Leal, Graciano

Bdnf exon-IV and exon-VI transcripts are driven by neuronal activity and are involved in pathologies related to sleep, fear or memory disorders. However, how their differential transcription translates activity changes into long-lasting network changes is elusive. Aiming to trace specifically the network controlled by exon-IV and -VI derived BDNF during activity-dependent plasticity changes, we generated a tran...


The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA M...

Leal, Graciano; Comprido, Diogo; Luca, Pasqualino De; Morais, Eduardo Manuel Firmo; Rodrigues, Luís; Mele, Miranda; Santos, Ana R.; Costa, Rui O.

Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K ...


The RNA-binding protein hnRNP K mediates the effect of BDNF on dendritic mRNA m...

Leal, Graciano; Comprido, Diogo; Luca, Pasqualino de; Morais, Eduardo; Rodrigues, Luís; Mele, Miranda; Santos, Ana R.; Costa, Rui O.; Pinto, Maria Joana

Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K ...


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