11 documents found, page 1 of 2
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, NunoIn 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...
Selective modulation of epileptic tissue by an adenosine A3 receptor‐activating...
Ghosh, Anwesha; Ribeiro Rodrigues, Leonor; Ruffolo, Gabriele; Alfano, Veronica; Domingos, Cátia; Rei, Nádia; Tosh, Dilip K.; Rombo, Diogo M.Background and purpose: Adenosine, through the A1 receptor (A1R), is an endogenous anticonvulsant. The development of adenosine receptor agonists as antiseizure medications has been hampered by their cardiac side effects. A moderately A1R-selective agonist, MRS5474, has been reported to suppress seizures without considerable cardiac action. Hypothesizing that this drug could act through other than A1R and/or th...
Caffeine has a dual influence on NMDA receptor–mediated glutamatergic transmiss...
Silva Martins, Robertta; Rombo, Diogo M.; Gonçalves-Ribeiro, Joana; Meneses, Carlos; Borges-Martins, Vladimir P. P.; Ribeiro, Joaquim A.; Vaz, Sandra H.Caffeine, a stimulant largely consumed around the world, is a non-selective adenosine receptor antagonist, and therefore caffeine actions at synapses usually, but not always, mirror those of adenosine. Importantly, different adenosine receptors with opposing regulatory actions co-exist at synapses. Through both inhibitory and excitatory high-affinity receptors (A1R and A2R, respectively), adenosine affects NMDA...
Role of adenosine in epilepsy and seizures
Tescarollo, Fabio C.; Rombo, Diogo M.; DeLiberto, Lindsay K.; Fedele, Denise E.; Alharfoush, Enmar; Tomé, Ângelo R.; Cunha, Rodrigo A.; Sebastião, Ana MAdenosine is an endogenous anticonvulsant and neuroprotectant of the brain. Seizure activity produces large quantities of adenosine, and it is this seizure-induced adenosine surge that normally stops a seizure. However, within the context of epilepsy, adenosine plays a wide spectrum of different roles. It not only controls seizures (ictogenesis), but also plays a major role in processes that turn a normal brain...
Adenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal neurons
Mouro, Francisco; Rombo, Diogo M.; Dias, Raquel Baptista; Ribeiro, Joaquim A.; Sebastião, Ana MBackground and purpose: NMDA receptors play a key role in both synaptic plasticity and neurodegeneration. Adenosine is an endogenous neuromodulator and through membrane receptors of the A2A subtype can influence both synaptic plasticity and neuronal death. The present work was designed to evaluate the influence of adenosine A2A receptors upon NMDA receptor activity in CA1 hippocampal neurons. We discriminated b...
Ex vivo model of epilepsy in organotypic slices : a new tool for drug screening
Magalhães, Daniela; Pereira, Noémia; Rombo, Diogo M.; Beltrão-Cavacas, Cláudia; Sebastião, Ana M; Valente, Cláudia A.Background: Epilepsy is a prevalent neurological disorder worldwide. It is characterized by an enduring predisposition to generate seizures and its development is accompanied by alterations in many cellular processes. Organotypic slice cultures represent a multicellular environment with the potential to assess biological mechanisms, and they are used as a starting point for refining molecules for in vivo studie...
Enhanced LTP in aged rats: detrimental or compensatory?
Pinho, Júlia; Vale, Ruben; Batalha, Vânia; Costenla, Ana Rita; Dias, Raquel Baptista; Rombo, Diogo M.; Sebastião, Ana M; De Mendonça, AlexandreAge-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 GABAergic transmission: a new target for adenosine control of excit...
Rombo, Diogo M.; Ribeiro, Joaquim A.; Sebastião, Ana MPhysiological network functioning in the hippocampus is dependent on a balance between glutamatergic cell excitability and the activity of diverse local circuit neurons that release the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Tuners of neuronal communication such as adenosine, an endogenous modulator of synapses, control hippocampal network operations by regulating excitability. Evidence has bee...
Differential role of the proteasome in the early and late phases of BDNF-induce...
Santos, Ana Rita; Mele, Miranda; Vaz, Sandra H.; Kellermayer, Blanka; Grimaldi, Maddalena; Oliveira, Mariana; Rombo, Diogo M.; Comprido, DiogoThe neurotrophin brain-derived neurotrophic factor (BDNF) mediates activity-dependent long-term changes of synaptic strength in the CNS. The effects of BDNF are partly mediated by stimulation of local translation, with consequent alterations in the synaptic proteome. The ubiquitin-proteasome system (UPS) also plays an important role in protein homeostasis at the synapse by regulating synaptic activity. However,...
Extracellular Alpha-Synuclein Oligomers Modulate Synaptic Transmission and Impa...
Diógenes, Maria José; Dias, Raquel B.; Rombo, Diogo M.; Miranda, Hugo Vicente; Maiolino, Francesca; Guerreiro, Patrícia; Näsström, ThomasParkinson’s disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of -synuclein (a-syn) in various brain regions is themajorpathological hallmark. Indeed, themotorsymptomsinPDare causedby a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In a...