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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 Morais

The 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...


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 Mateus

Epidemiologic 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...


The influence of gliotransmission on higher cognitive functions

Sardinha, Vanessa Alexandra Morais

Tese de Doutoramento em Ciências da Saúde; In recent years, the understanding of synaptic modulation by neuron-astrocyte interactions has evolved considerably, contributing to build up the concept of the “tripartite synapse”. This concept is based on the dynamic dialogue between astrocytes and neurons that complements and modulates the communication between pre- and post-synaptic structures. However, it remains...


The nucleus reuniens: a key node in the neurocircuitry of stress and depression

Kafetzopoulos, V.; Kokras, N.; Sotiropoulos, I.; Oliveira, João F.; Leite-Almeida, Hugo; Vasalou, A.; Sardinha, Vanessa Alexandra Morais

Uncorrected proof; The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, p...


The role of astrocytic calcium signaling in the aged prefrontal cortex

Gomes, Sónia Isabel Nunes Guerra; Viana, João Filipe; Nascimento, Diana Sofia Marques; Correia, Joana Sofia Silva; Sardinha, Vanessa Alexandra Morais

Aging is a lifelong process characterized by cognitive decline putatively due to structural and functional changes of neural circuits of the brain. Neuron-glial signaling is a fundamental component of structure and function of circuits of the brain, and yet its possible role in aging remains elusive. Significantly, neuron-glial networks of the prefrontal cortex undergo age-related alterations that can affect co...


AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not a...

Pinheiro, António Maria Restolho Mateus; Alves, N. D.; Patrício, Patrícia Carvalho; Santos, Ana Rita Machado dos; Campos, E. Loureiro

Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ 3 (AP2γ 3, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP...


Employing an open-source tool to assess astrocyte tridimensional structure

Tavares, Gabriela Pires; Martins, Manuella Mendes; Correia, Joana Sofia Silva; Sardinha, Vanessa Alexandra Morais; Gomes, Sónia Isabel Nunes Guerra

Astrocytes display important features that allow them to maintain a close dialog with neurons, ultimately impacting brain function. The complex morphological structure of astrocytes is crucial to the role of astrocytes in brain networks. Therefore, assessing morphologic features of astrocytes will help provide insights into their physiological relevance in healthy and pathological conditions. Currently availabl...


Adenosine A2A receptor regulation of microglia morphological remodeling-gender ...

Caetano, L.; Pinheiro, H.; Patrício, Pedro; Mateus-Pinheiro, A.; Alves, N. D.; Coimbra, B.; Baptista, F. I.; Henriques, S. N.; Cunha, C.; Santos, A. R.

Developmental risk factors, such as the exposure to stress or high levels of glucocorticoids (GCs), may contribute to the pathogenesis of anxiety disorders. The immunomodulatory role of GCs and the immunological fingerprint found in animals prenatally exposed to GCs point towards an interplay between the immune and the nervous systems in the etiology of these disorders. Microglia are immune cells of the brain, ...


Astrocytic signaling supports hippocampal-prefrontal theta synchronization and ...

Sardinha, Vanessa Alexandra Morais; Gomes, Sónia Isabel Nunes Guerra; Campos, Inês Caetano Costa; Tavares, Gabriela Pires; Martins, Manuella Mendes

Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function; Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corti...


Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits a...

Lopes, Sofia Oliveira; Lopes, André Teixeira; Pinto, Vítor Manuel Silva; Guimarães, Marco Rafael; Sardinha, Vanessa Alexandra Morais; Silva, Sara Duarte

Dementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well-established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been inc...


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