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Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebel...
Correia, Joana Sofia Silva; Carvalho, Andreia Alexandra Neves; Pinheiro, Bárbara Filipa Mendes; Pires, Joel Pereira; Teixeira, Fábio Gabriel RodriguesThe low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)—or Machado–Joseph disease (MJD)—is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathop...
Low-cost silicon neural probe: fabrication, electrochemical characterization an...
Rodrigues, José Artur Oliveira; Pimenta, Sara; Pereira, José P.; Gomes, Nuno M.; Souto, Márcio R.; Fernandes, Helena C.; Caetano, InêsThis paper presents the fabrication of a silicon neural probe using low-cost microfabrication technologies, such as thin-films deposition, blade dicing, and photolithography. The metal stack that forms the 9 microelectrodes of 50 × 50 µm2 area, the tracks and the pads were made of Ti and Pt, while the passivation stack was SiO2 and Si3N4. The fabricated probe was characterized using electrochemical impedance sp...
Unilateral intrastriatal 6-hydroxydopamine lesion in mice: a closer look into n...
Pinheiro, Bárbara Filipa Mendes; Cunha, Carina Isabel Soares; Marote, Ana Maria Franco Aveiro; Loureiro-Campos, Eduardo; Campos, Jonas OliveiraParkinson’s disease (PD) is a prevalent movement disorder characterized by the progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). The 6-hydroxydopamine (6-OHDA) lesion is still one of the most widely used techniques for modeling Parkinson’s disease (PD) in rodents. Despite commonly used in rats, it can be challenging to reproduce a similar lesion in mice. Moreover, there is a lac...
Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes a...
Loureiro-Campos, Eduardo; Mateus-Pinheiro, António; Patrício, Patrícia; Cunha, Carina Isabel Soares; Silva, Joana; Sardinha, Vanessa Alexandra MoraisThe transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early post...
Dysregulation of autophagy and stress granule-related proteins in stress-driven...
Silva, Joana Margarida Gonçalves Mota; Rodrigues, Sara; Marques, Maria Belém Sousa Sampaio; Gomes, Patrícia; Carvalho, Andreia Alexandra NevesImbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer's disease (AD) and other Tauopathies. Consistent with suggestions that lifetime stress may be an important AD precipitating factor, we previously reported that environmental stress and high glucocorticoid (GC) levels induce accumulation of aggregated Tau; however, the m...
Region-specific control of microglia by adenosine A2A receptors: uncoupling anx...
Duarte, Joana Mendes; Gaspar, Rita; Caetano, Liliana; Patrício, Patrícia; Cunha, Carina Isabel Soares; Pinheiro, António Maria Restolho MateusEpidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a cor...
Mild prenatal stress causes emotional and brain structural modifications in rat...
Cunha, Carina Isabel Soares; Coimbra, Bárbara Guimarães Salazar; Borges, Sónia; Domingues, Ana Verónica; Silva, Deolinda; Sousa, NunoStress or high levels of glucocorticoids (GCs) during developmental periods is known to induce persistent effects in the neuroendocrine circuits that control stress response, which may underlie individuals' increased risk for developing neuropsychiatric conditions later in life, such as anxiety or depression. We developed a rat model (Wistar han) of mild exposure to unpredictable prenatal stress (PS), which con...
Neuroprotective effects of creatine in the CMVMJD135 mouse model of Spinocerebe...
Silva, Sara Carina Duarte; Carvalho, Andreia Alexandra Neves; Cunha, Carina Isabel Soares; Silva, Joana M.; Castro, Andreia Cristiana TeixeiraBackground and Objective: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine‐enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which ...
Endolysosomal degradation of Tau and its role in glucocorticoid-driven hippocam...
Vaz-Silva, João; Gomes, Patrícia; Jin, Qi; Zhu, Mei; Zhuravleva, Viktoriya; Quintremil, Sebastian; Meira, Torcato Duarte Novo; Silva, JoanaEmerging studies implicate Tau as an essential mediator of neuronal atrophy and cognitive impairment in Alzheimer's disease (AD), yet the factors that precipitate Tau dysfunction in AD are poorly understood. Chronic environmental stress and elevated glucocorticoids (GC), the major stress hormones, are associated with increased risk of AD and have been shown to trigger intracellular Tau accumulation and downstre...
Nucleus accumbens microcircuit underlying D2-MSN-Driven increase in motivation
Cunha, Carina Isabel Soares; Coimbra, Bárbara Guimarães Salazar; Domingues, Ana Verónica; Vasconcelos, Nivaldo António Portela; Sousa, NunoThe nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects ...