Begoña Villar-ChedaUniversity of Santiago de Compostela | USC · Department of Morphological Sciences
Begoña Villar-Cheda
PhD
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43
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Publications (43)
The brain renin-angiotensin system (RAS) has been related to dopaminergic degeneration, and high expression of the angiotensin II (AngII) type 1 receptor (AT1) gene is a marker of the most vulnerable neurons in humans. However, it is unknown whether AngII/AT1 overactivation affects α-synuclein aggregation and transmission. In vitro, AngII/AT1 activ...
The tissue renin-angiotensin system (RAS) has been shown to be involved in prooxidative and proinflammatory changes observed in aging and aging-related diseases such as dopaminergic degeneration in Parkinson's disease (PD). We studied the activation of the NLRP3 inflammasome in the substantia nigra with aging and early stages of dopaminergic degene...
Dysregulation of the tissue renin–angiotensin system (RAS) is involved in tissue oxidative and inflammatory responses. Among RAS components, renin, its precursor (pro)renin and its specific receptor (PRR) have been less investigated, particularly in the brain. We previously showed the presence of PRR in neurons and glial cells in the nigrostriatal...
The renin-angiotensin system (RAS) is one of the oldest hormone systems in vertebrate phylogeny. RAS was initially related to regulation of blood pressure and sodium and water homeostasis. However, local or paracrine RAS were later identified in many tissues, including brain, and play a major role in their physiology and pathophysiology. In additio...
Sirtuin 3 (SIRT3) and angiotensin play a major role in aging-related disorders. Both modulate oxidative stress and neurodegeneration. We investigated the interaction between SIRT3 and angiotensin II (AngII) in the dopaminergic system. Both in vivo and in vitro, treatment with AngII decreased SIRT3 expression, which was reversed by angiotensin type...
In addition to the classical hormonal (tissue-to-tissue) renin-angiotensin system (RAS), there are a paracrine (cell-to-cell) and an intracrine (intracellular/nuclear) RAS. A local paracrine brain RAS has been associated with several brain disorders, including Parkinson’s disease (PD). Classically, angiotensin II (Ang II) is the main RAS effector p...
Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinf...
The ‘classical’ renin–angiotensin system (RAS) is a circulating system that controls blood pressure. Local/paracrine RAS, identified in a variety of tissues, including the brain, is involved in different functions and diseases, and RAS blockers are commonly used in clinical practice. A third type of RAS (intracellular/intracrine RAS) has been obser...
The renin–angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the ‘classical’ humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and agin...
Abnormal activation of the RhoA/Rho kinase (ROCK) pathway plays a pivotal role in neuroinflammatory and pro-oxidative responses,
axonal retraction, and apoptosis. We observed increased expression of RhoA, ROCK II, and ROCK activity in the brain of aged
rats, particularly in the substantia nigra. Increased ROCK activity may enhance major mechanisms...
The small GTP-binding protein Rho plays an important role in several cellular functions. RhoA, which is a member of the Rho family, initiates cellular processes that act on its direct downstream effector Rho-associated kinase (ROCK). ROCK inhibition protects against dopaminergic cell death induced by dopaminergic neurotoxins. It has been suggested...
Several recent studies have shown that activation of the RhoA/Rho-associated kinase (ROCK) pathway is involved in the MPTP-induced dopaminergic cell degeneration and possibly in Parkinson's disease. ROCK inhibitors have been suggested as candidate neuroprotective drugs for Parkinson's disease. However, the mechanism responsible for the increased su...
Renin-angiotensin systems are known to act in many tissues, for example, the blood vessel wall or kidney, where a close interaction between angiotensin and dopamine has been demonstrated. Regulatory interactions between the dopaminergic and renin-angiotensin systems have recently been described in the substantia nigra and striatum. In animal models...
Beneficial effects of angiotensin type-1 receptor (AT1) inhibition have been observed in a number of brain processes mediated by oxidative stress and neuroinflammation, including Parkinson's disease. However, important counterregulatory interactions between dopamine and angiotensin systems have recently been demonstrated in several peripheral tissu...
The pathogenic mechanism of Parkinson's disease (PD) appears to be multifactorial. However, oxidative stress and neuroinflammation, including activation of NADPH-dependent oxidases, play a major role in the progression of dopaminergic cell death. The renin-angiotensin system (RAS) was described as a circulating humoral system that regulates blood p...
It has recently been shown that the dopaminergic cell loss induced by neurotoxins is enhanced by brain angiotensin II (AII) via type 1 receptors (AT1). However, the mechanisms involved in the dopaminergic degeneration and the brain inflammatory effects of AII have not been clarified. The RhoA-Rho-Kinase (ROCK) pathway may play a critical role in th...
We have previously obtained in rodents a considerable amount of data suggesting a major role for the brain renin-angiotensin system (RAS) in dopaminergic neuron degeneration and potentially in Parkinson's disease. However, the presence of a local RAS has not been demonstrated in the monkey or the human substantia nigra compacta (SNc). The present s...
There is a lack of consensus about the effects of the type of menopause (surgical or natural) and of oestrogen replacement therapy on Parkinson's disease. The effects of the timing of replacement therapy and the female's age may explain the observed differences in such effects. However, the mechanisms involved are poorly understood. The renin-angio...
For years, the renin-angiotensin system (RAS) was described as a circulating humoral system that regulates blood pressure and water homeostasis. Angiotensin II (AII) is the most important effector peptide. However, in addition to the "classical" humoral RAS there exist local RAS in many tissues and locally formed AII activates NADPH-dependent oxida...
Angiotensin II acts via angiotensin type 1 receptors and is a major inducer of inflammation and oxidative stress. Local renin-angiotensin systems play a major role in the development of age-related disorders in several tissues. These processes are delayed, but not totally abolished, by blockade of angiotensin signaling. A specific receptor for reni...
The basal ganglia have a local renin-angiotensin system and it has been shown that the loss of dopaminergic neurons induced by neurotoxins is amplified by local angiotensin II (AII) via angiotensin type 1 receptors (AT1) and nicotinamide adenine dinucleotide phosphate (NADPH) complex activation. Recent studies have revealed a high degree of counter...
An age-related proinflammatory, pro-oxidant state in the nigra may increase the vulnerability of dopaminergic neurons to additional damage. Angiotensin II, via type 1 (AT1) receptors, is one of the most important known inflammation and oxidative stress inducers. However, it is not known if there are age-related changes in the nigral angiotensin sys...
Epidemiological studies have reported that the incidence of Parkinson's disease (PD) is higher in postmenopausal than in premenopausal women of similar age. Several laboratory observations have revealed that estrogen has protective effects against dopaminergic toxins. The mechanism by which estrogen protects dopaminergic neurons has not been clarif...
Neuroactive substances such as serotonin and other monoamines have been suggested to be involved in the transmission of gustatory signals from taste bud cells to afferent fibers. Lampreys are the earliest vertebrates that possess taste buds, although these differ in structure from taste buds in jawed vertebrates, and their neurochemistry remains un...
It is not known if aging induces changes in nigral vascularization and nigral vascular endothelial growth factor (VEGF) levels similar to those previously reported for Parkinson's disease (PD). In this study nonexercised rats displayed age-dependent decreases in the density of nigral microvessels and VEGF mRNA expression, which were reversed by phy...
Brain regionalization has been extensively studied in tetrapods, teleosts and cyclostomes. In contrast, it has not been investigated in elasmobranchs, despite their key phylogenetic position to understand brain evolution in jawed vertebrates. In this study we provide a schematic view of the segmental pattern of the developing shark brain based on m...
Lamprey eyes exhibit dual retinal development, with highly different larval and adult phases. Here, cell proliferation and photoreceptor differentiation was investigated in late larvae and during transformation (occurring several years after egg hatching) by using immunohistochemistry against the proliferating cell nuclear antigen (PCNA) and opsins...
The sea lamprey is a modern representative of the earliest vertebrates (the agnathans) in which development of the eye and retina shows unique patterns. In larval stages the retina is poorly developed, and although a small central region has developed glutamatergic vertical pathways, there is no evidence of chemical differentiation of amacrine and...
The development of the early axonal scaffold formed by early-differentiating neurons was studied in a primitive vertebrate (the sea lamprey), by immunohistochemistry against acetylated alpha-tubulin and a cell surface marker (HNK-1 antibodies), to determine the degree of conservation of this process in vertebrate evolution. The medial and dorsolate...
Lampreys belong to the most primitive extant group of vertebrates, the Agnathans, which is considered the sister group of jawed vertebrates. Accordingly, characterization of neuronal groups and their development appears useful for understanding early evolution of the nervous system in vertebrates. Here, the development of the serotonergic system in...
The neurochemistry of the retina of the larval and postmetamorphic sea lamprey was studied via immunocytochemistry using antibodies directed against the major candidate neurotransmitters [glutamate, glycine, gamma-aminobutyric acid (GABA), aspartate, dopamine, serotonin] and the neurotransmitter-synthesizing enzyme tyrosine hydroxylase. Immunoreact...
Cell proliferation in the forebrain and midbrain of the sea lamprey (Petromyzon marinus L.) was investigated by proliferation cell nuclear antigen (PCNA) immunocytochemistry, with BrdU labeling as a complementary technique. Correspondence between proliferation regions and areas of early neuronal differentiation was also assessed using antibodies ag...
The presence of calretinin and calbindin immunoreactivity is studied in the retina of larval and adult lamprey and their respective distributions are compared. Calretinin distribution is also studied in the retina of transforming stages. Western blot analysis in brain extracts showed a 29-kDa band with both polyclonal anti-calbindin and anti-calret...
The diencephalic/midbrain tegmental domain of the developing lamprey was characterized by the special features of the ventricular zone and distribution of some postmitotic neuronal populations, using proliferating cell nuclear antigen (PCNA) and HNK-1 immunocytochemistry. In late prolarvae and early larvae, the tegmental ventricular zone differenti...
We studied the organization of the dorsal column nucleus (DCN) of larval sea lamprey with immunohistochemical and tract-tracing techniques. Texas red-coupled dextran amine was injected into the spinal cord, which allowed tracing the dorsal column fibers and characterizing the DCN. The dorsal column fibers formed a dense tract coursing adjacent to t...
The development of dopamine-immunoreactive (DAir) populations in the central nervous system of the sea lamprey, a modern representative of the earliest vertebrates, was studied to achieve further understanding of dopaminergic systems in vertebrates. The first DAir cell groups appeared in the spinal cord, the posterior tubercle nucleus and the dorsa...
The development of neurons expressing gamma-aminobutyric acid (GABA) in the rhombencephalon and spinal cord of the sea lamprey (Petromyzon marinus) was studied for the first time with an anti-GABA antibody. The earliest GABA-immunoreactive (GABAir) neurons appear in late embryos in the basal plate of the isthmus, caudal rhombencephalon, and rostral...
Although brain organization in lampreys is of great interest for understanding evolution in vertebrates, knowledge of early development is very scarce. Here, the development of the forebrain and midbrain gamma-aminobutyric acid (GABA)-ergic systems was studied in embryos, prolarvae, and small larvae of the sea lamprey using an anti-GABA antibody. A...
The development of the pineal complex and the habenula of the sea lamprey was studied with proliferating cell nuclear antigen (PCNA) immunocytochemistry. The pineal organ and the habenula primordia appeared in late embryos, and neuron differentiation began in prolarvae, as indicated by the presence of PCNA-negative cells. The parapineal primordium...
Lampreys have a complex life cycle, with largely differentiated larval and adult periods. Despite the considerable interest of lampreys for understanding vertebrate evolution, knowledge of the early development of their eye and pineal complex is very scarce. Here, the early immunocytochemical organization of the pineal complex and retina of the sea...