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Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity ...
Gonzalez-Ramos, Ana; Berglind, Fredrik; Kudláček, Jan; Ribeiro Rocha, Elza; Melin, Esbjörn; Sebastião, Ana M; Valente, Cláudia A.; Ledri, MarcoDespite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator u...
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...
Age-related impact of social isolation in mice: young vs middle-aged
Magalhães, Daniela M; Mampay, Myrthe; Sebastião, Ana M; Sheridan, Graham K.; Valente, Cláudia A.Social isolation is a chronic mild stressor and a significant risk factor for mental health disorders. Herein we explored the impact of social isolation on depression- and anxiety-like behaviours, as well as spatial memory impairments, in middle-aged male mice compared to post-weaning mice. We aimed to quantify and correlate social isolation-induced behaviour discrepancies with changes in hippocampal glial cell...
Changes in adenosine receptors and neurotrophic factors in the SOD1G93A mouse m...
Rei, Nádia; Valente, Cláudia A.; Vaz, Sandra H.; Farinha-Ferreira, Miguel; Ribeiro, Joaquim A.; Sebastião, Ana M.Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of corticospinal tract motor neurons. Previous studies showed that adenosine-mediated neuromodulation is disturbed in ALS and that vascular endothelial growth factor (VEGF) has a neuroprotective function in ALS mouse models. We evaluated how adenosine (A1R and A2AR) and VEGF (VEGFA, VEGFB, VEGFR-1 and VEGFR-2) system markers ar...
A model of epileptogenesis in rhinal cortex-hippocampus organotypic slice cultures
Valente, Cláudia A.; Meda, Francisco; Carvalho, Mafalda; Sebastião, Ana MOrganotypic slice cultures have been widely used to model brain disorders and are considered excellent platforms for evaluating a drug's neuroprotective and therapeutic potential. Organotypic slices are prepared from explanted tissue and represent a complex multicellular ex vivo environment. They preserve the three-dimensional cytoarchitecture and local environment of brain cells, maintain the neuronal connecti...
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced ...
Belo, Rita F.; Martins, Margarida L. F.; Shvachiy, Liana; Costa-Coelho, Tiago; de Almeida-Borlido, Carolina; Fonseca-Gomes, João; Neves, VeraKyotorphin (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.c.v.) injection of KTP ameliorates memor...
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...
BDNF modulates glycine uptake in hippocampal synaptosomes by decreasing membran...
Aroeira, Rita I.; Vaz, Sandra H.; Sebastião, Ana M; Valente, Cláudia A.Glycine transporter 2 (GlyT2) is localized in the nerve terminals of glycinergic neurons, promoting glycine uptake and ensuring the refilling of glycinergic vesicles. Brain-derived neurotrophic factor (BDNF) activates its high affinity TrkB receptors, which occur in two isoforms, full length (TrkB-FL) and truncated (TrkB-T1/T2). After BDNF binding to TrkB receptor, several intracellular cascades are triggered, ...
BDNF, via truncated TrkB receptor, modulates GlyT1 and GlyT2 in astrocytes
Aroeira, Rita I.; Sebastião, Ana M; Valente, Cláudia A.Glycine transporters (GlyT), GlyT1 and GlyT2, are responsible for the termination of glycine-mediated synaptic activity through removal of neurotransmitter from synaptic cleft. Brain-derived neurotrophic factor (BDNF) activates its high affinity tropomyosin-related kinase (Trk) receptors, namely TrkB, which includes full length (TrkB-FL) and truncated (TrkB-T) isoforms. In this article we evaluated the influenc...
Dysregulation of TrkB receptors and BDNF function by amyloid-β peptide is media...
Jerónimo-Santos, André; Vaz, Sandra H.; Parreira, Sara; Lerias, Sofia; Caetano, António P.; Buée-Scherrer, Valérie; Castrén, Eero; Valente, Cláudia A.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 decr...