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Impairment of spatial working memory but preservation of recognition memory in ...

Neuparth-Sottomayor, Mariana; Morais, Tatiana P.; Good, Mark; Sebastião, Ana M; Di Giovanni, Giuseppe; Crunelli, Vincenzo; Vaz, Sandra H.

Epidemiological studies reveal gender-specific differences in epilepsy. Childhood absence epilepsy (CAE), which is more prevalent in females, is characterized by typical absence seizures (ASs) consisting of brief periods of unconsciousness, associated with 2.5-4 Hz spike-wave discharges (SWDs) in the electroencephalogram (EEG). Children with CAE often present neuropsychological comorbidities, including deficits...


Cleavage of the TrkB-FL receptor during epileptogenesis: insights from a kainic...

Ribeiro Rodrigues, Leonor; Fonseca-Gomes, João; Paulo, Sara L; Viais, Ricardo; Ribeiro, Filipa; Miranda-Lourenço, Catarina; Mouro, Francisco

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity. In epilepsy, BDNF exhibits a dual role, exerting both antiepileptic and pro-epileptic effects. The cleavage of its main receptor, full-length tropomyosin-related kinase B (TrkB-FL), was suggested to occur in status epilepticus (SE) in vitro. Moreover, under excitotoxic conditions, TrkB-FL was found to b...


Concurrent stress modulates the acute and post-acute effects of psilocybin in a...

Farinha Ferreira, Jorge Miguel; Miranda-Lourenço, Catarina; Galipeau, Chloé; Lenkei, Zsolt; Sebastião, Ana M

There is renewed interest in psychedelics, such as psilocybin, as therapies for multiple difficult-to-treat psychiatric disorders. Even though psychedelics can induce highly pleasant or aversive experiences, depending on multiple personal and environmental factors, there is little research into how such experiences impact post-acute mood-altering actions. Here we aimed at offsetting this gap. First, we tested w...


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...


Brain-derived neurotrophic factor modulation in response to oxidative stress an...

Correia, Ana Salomé; Torrado, Marília; Costa-Coelho, Tiago; Carvalho, Eva Daniela; Inteiro-Oliveira, Sara; Diógenes, Maria José; Pêgo, Ana Paula

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. Aim: This manuscript aims to explore the complex relationship between MDD and BDNF signal...


Neuroprotective effects of platinum nanoparticle-based microreactors in bicucul...

Oliveira, Roberto N.; Carvalhinho-Lopes, Patrícia S.; Carvalho, Carolina P. F.; Hirata, Rafael Y. S.; Vaz, Sandra H.; Sebastião, Ana M

Epilepsy designates a group of chronic brain disorders, characterized by the recurrence of hypersynchronous, repetitive activity, of neuronal clusters. Epileptic seizures are the hallmark of epilepsy. The primary goal of epilepsy treatment is to eliminate seizures with minimal side effects. Nevertheless, approximately 30% of patients do not respond to the available drugs. An imbalance between excitatory/inhibit...


Unmoving and uninflamed: characterizing neuroinflammatory dysfunction in the Wi...

Farinha Ferreira, Jorge Miguel; Magalhães, Daniela M; Neuparth-Sottomayor, Mariana; Rafael, H.; Miranda-Lourenço, Catarina; Sebastião, Ana M

Reductionistic research on depressive disorders has been hampered by the limitations of animal models. Recently, it has been hypothesized that neuroinflammation is a key player in depressive disorders. The Wistar-Kyoto (WKY) rat is an often-used animal model of depression, but no information so far exists on its neuroinflammatory profile. As such, we compared male young adult WKY rats to Wistar (WS) controls, w...


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, Marco

Despite 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...


Adenosine receptors are the on‐and‐off switch of astrocytic cannabinoid type 1 ...

Gonçalves-Ribeiro, Joana; Savchak, Oksana K.; Pinto, Sara; Gomes, Joana I.; Rivas‐Santisteban, Rafael; Lillo, Alejandro; Sánchez Romero, Javier

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further...


Lineage-specific changes in mitochondrial properties during neural stem cell di...

Soares, Rita; Lourenço, Diogo M.; F. Mota, Isa; Sebastião, Ana M; Xapelli, Sara; Morais, Vanessa A.

Neural stem cells (NSCs) reside in discrete regions of the adult mammalian brain where they can differentiate into neurons, astrocytes, and oligodendrocytes. Several studies suggest that mitochondria have a major role in regulating NSC fate. Here, we evaluated mitochondrial properties throughout NSC differentiation and in lineage-specific cells. For this, we used the neurosphere assay model to isolate, expand, ...


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