40 documents found, page 1 of 4
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, FranciscoBrain-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...
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...
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 PaulaMajor 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...
Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hal...
Nunes, Maria João; Carvalho, Andreia N.; Reis, Joana; Costa, Daniela; Moutinho, Miguel; Mateus, Joana; Mendes de Almeida, Rita; Brito, SaraCholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 co...
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...
Spatiotemporal dysregulation of neuron-glia related genes and pro-/anti-inflamm...
Ianni, Marta; Corraliza-Gomez, Miriam; Costa-Coelho, Tiago; Ferreira-Manso, Mafalda; Inteiro-Oliveira, Sara; Alemãn-Serrano, Nuno; Sebastião, Ana MAlzheimer's disease (AD), the leading cause of dementia, is a multifactorial disease influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators of gene expression and play significant roles in AD onset and progression. This exploratory study analyzed the expression levels of 28 genes and 5 miRNAs (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, and miR-155-5p) related to AD patholo...
Adenosinergic system and BDNF signaling changes as a cross-sectional feature of...
Miranda-Lourenço, Catarina; Rosa, Jéssica; Rei, Nádia; Belo, Rita F.; Lopes, Ana Luísa; Silva, Diogo; Vieira, Cátia; Magalhães-Cardoso, TeresaRett Syndrome is an X-linked neurodevelopmental disorder (RTT; OMIM#312750) associated to MECP2 mutations. MeCP2 dysfunction is seen as one cause for the deficiencies found in brain-derived neurotrophic factor (BDNF) signaling, since BDNF is one of the genes under MeCP2 jurisdiction. BDNF signaling is also dependent on the proper function of the adenosinergic system. Indeed, both BDNF signaling and the adenosin...
Astrocytes control hippocampal synaptic plasticity through the vesicular-depend...
Abreu, Daniela Sofia; Gomes, Joana I.; Ribeiro, Filipa; Diógenes, Maria José; Sebastião, Ana M; Vaz, Sandra H.Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic pl...
S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early ...
Ferreira, Catarina B.; Marttinen, Mikael; Coelho, Joana E; Paldanius, Kaisa M.A.; Takalo, Mari; Mäkinen, Petra; Leppänen, LuukasAlzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynap...
Sustained hippocampal neural plasticity questions the reproducibility of an amy...
Paulo, Sara L; Ribeiro Rodrigues, Leonor; Rodrigues, Rui S.; Mateus, Joana; Fonseca-Gomes, João; Soares, Rita; Diógenes, Maria José; Solá, SusanaBackground: The use of Alzheimer's disease (AD) models obtained by intracerebral infusion of amyloid-β (Aβ) has been increasingly reported in recent years. Nonetheless, these models may present important challenges. Objective: We have focused on canonical mechanisms of hippocampal-related neural plasticity to characterize a rat model obtained by an intracerebroventricular (icv) injection of soluble amyloid-β42 ...