Biology subjects

Medina, L.

Publications and source records attributed to Medina, L..

8 recordsLinked to original sources

bioRxiv2025

Postnatal plasticity in the olfactory system of the juvenile swine brain

Swine have an excellent sense of smell and highly complex olfactory brain structures, which play a crucial role in their complex social interactions. In other mammals the olfactory system is known to exhibit significant plasticity, even during adulthood. The aim of this study was to investigate postnatal plasticity in olfactory areas of juvenile swine brains by studying immature cells immunoreactive for the microtubule-associated protein doublecortin (DCX). Using immunofluorescence, we studied DCX coexpression with the cell proliferation marker Ki-67, and different neuronal markers. Our results show the existence of numerous DCX+ cells throughout the olfactory pallial areas. In some of them, we found DCX+/Ki-67+ coexpressing cells, suggesting that they were proliferating. Some of these proliferating cells were grouped in tangentially-oriented migratory-like chains, forming the rostral migratory stream to anterior olfactory area and olfactory bulb. Moreover, chains of DCX+ cells were found in the external capsule and white matter adjacent to the temporal horn of the ventricle. Chains of DCX+ cells were observed crossing the internal layers of the piriform and entorhinal cortices. In layer II of these cortices, DCX+ cells of varying maturity degrees and neuronal phenotypes (including NeuN expression) were present. This suggests the existence of multiple migratory streams along the anteroposterior axis. Most DCX+ immature cells in the migratory chains and in the anterior olfactory area, piriform and entorhinal cortices expressed the transcription factor Brn2 (Pou3f2), suggesting the incorporation of new glutamatergic neurons in these areas. Together, these results highlight the interest of swine to study the role of postnatal brain plasticity and their potential for regeneration in large, gyrencephalic brains.

neuroscience↗

bioRxiv2025

Development of catecholaminergic neurons of Otp-lineage in the medial extended amygdala and other centers of the social behavior network

Catecholaminergic (CA) neurons of the medial extended amygdala, preoptic region and adjacent alar hypothalamus have been involved in different aspects of social behavior. Previous data suggested that at least some CA neurons of the medial extended amygdala could originate in a hypothalamic embryonic domain that expresses the transcription factor Otp. To investigate this, we used Otp-eGFP mice to analyze coexpression of GFP and tyrosine hydroxylase (TH) throughout ontogenesis by way of double immunofluorescence. Our results showed that some TH cells coexpress GFP in the medial extended amygdala preoptic region, and alar and basal hypothalamus. However, the presence of TH/GFP double-labeled cells in the extended amygdala is transient, as they are not seen in adults. Based on previous data, the Otp-related CA cells of the medial extended amygdala might derive from the telencephalon-opto-hypothalamic domain, and those of the central paraventricular and supraoptic hypothalamic nuclei likely derive from the supraopto-paraventricular hypothalamic core domain. Taken together, these data provide new evidence for several Otp-related CA subpopulations in centers of the social brain network. The results open interesting questions about the role of these catecholaminergic subpopulations during the development and in different aspects of social behavior.

neuroscience↗

bioRxiv2024

Expression of sex steroid receptors and sex differences of Otp glutamatergic neurons of the medial extended amygdala

The medial extended amygdala (EAme) is part of the social behavior network and its subdivisions show expression of sex steroid receptors, which participate in the regulation of sexually dimorphic behaviors. However, EAme subdivisions are highly heterogeneous in terms of neuron subtypes, with different subpopulations being involved in regulation of different aspects of social and non-social behaviors. To further understand the role of the different EAme neurons and their contribution to sexual differences, here we studied one of its major subtypes of glutamatergic neurons, those derived from the telencephalon-opto-hypothalamic domain that coexpress Otp and Foxg1 genes during development. Our results showed that the vast majority of the Otp glutamatergic neurons of the medial amygdala and BSTM in both sexes express Ar, Esr1 (ER) and Esr2 (ER{beta}) mRNA. Moreover, the high percentage of receptors expression in the Otp neurons (between 93 and 100%) indicates that probably the majority of the Otp neurons of EAme are coexpressing the three receptors. In addition, Otp neurons of the posterodorsal medial amygdala have a larger soma and occupy more space in males than in females. These and other features of the Otp neurons regarding their expression of sex steroid receptors likely contribute to some of the sexually-dimorphic behaviors regulated by EAme.

neuroscience↗

bioRxiv2023

Subpopulations of corticotropin-releasing factor containing neurons and internal circuits in the chicken central extended amygdala

In mammals, the central extended amygdala is critical for regulation of the stress response. This regulation is extremely complex, involving multiple subpopulations of GABAergic neurons and complex networks of internal and external connections. Two neuron subpopulations expressing corticotropin-releasing factor (CRF), located in the central amygdala and the lateral bed nucleus of the stria terminalis (BSTL), play key roles in the long-term components of fear learning and in sustained fear responses akin to anxiety. Very little is known on the regulation of stress by the amygdala in non-mammals, hindering efforts for trying to improve animal welfare. In birds, one of the major problems relates to the high evolutionary divergence of the telencephalon, where the amygdala is located. In the present study, we aimed to investigate the presence of CRF neurons of the central extended amygdala in chicken and the local connections within this region. We found two major subpopulations of CRF cells in BSTL and the medial capsular central amygdala of chicken. Based on multiple labeling of CRF mRNA with different developmental transcription factors, all CRF neurons seem to originate within the telencephalon since they express Foxg1, and there are two subtypes with different embryonic origins that express Islet1 or Pax6. In addition, we demonstrated direct projections from Pax6 cells of the capsular central amygdala to BSTL and the oval central amygdala. We also found projections from Islet1 cells of the oval central amygdala to BSTL, which may constitute an indirect pathway for regulation of BSTL output cells. Part of these projections may be mediated by CRF cells, in agreement with expression of CRF receptors in both Ceov and BSTL. Our results show a complex organization of the central extended amygdala in chicken, and open new venues for studying how different cells and circuits regulate stress in these animals.

neuroscience↗

bioRxiv2023

Mapping of corticotropin-releasing factor, receptors and binding protein mRNA in the chicken telencephalon throughout ontogeny

Understanding the neural mechanisms that regulate the stress response is critical to know how animals adapt to a changing world and is one of the key factors to be considered for improving animal welfare. Corticotropin releasing factor (CRF) is crucial for regulating physiological and endocrine responses, triggering the activation of the sympathetic nervous system and the hypothalamo - pituitary - adrenal axis (HPA) during stress. In mammals, several telencephalic areas, such as the amygdala and the hippocampus, regulate the autonomic system and the HPA responses. These centers include subpopulations of CRF containing neurons that, by way of CRF receptors, play modulatory roles in the emotional and cognitive aspects of stress. CRF binding protein also plays a role, buffering extracellular CRF and regulating its availability. CRF role in activation of the HPA is evolutionary conserved in vertebrates, highlighting the relevance of this system to help animals cope with adversity. However, knowledge on CRF systems in the avian telencephalon is very limited, and no information exists on detailed expression of CRF receptors and binding protein. Knowing that the stress response changes with age, with important variations during the first week posthatching, the aim of this study was to analyze mRNA expression of CRF, CRF receptors 1 and 2, and CRF binding protein in chicken telencephalon throughout embryonic and early posthatching development, using in situ hybridization. Our results demonstrate an early expression of CRF and its receptors in pallial areas regulating sensory processing, sensorimotor integration and cognition, and a late expression in subpallial areas regulating the stress response. However, CRF buffering system develops earlier in the subpallium than in the pallium. These results help to understand the mechanisms underlying the negative effects of noise and light during prehatching stages in chicken, and suggest that stress regulation becomes more sophisticated with age.

neuroscience↗

bioRxiv2020

Doxycycline interferes with tau amyloid aggregation abolishing its associated neuronal toxicity

Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts -synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the different isoforms of tau protein in a dose-dependent manner, remodeling the resultant species. Furthermore, doxycycline interacts with tau microtubule-binding domain preventing its aggregation. In a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.

biophysics↗

bioRxiv2020

A novel telencephalon-opto-hypothalamic morphogenetic domain produces most of the glutamatergic neurons of the medial extended amygdala

Deficits in social cognition and behavior are a hallmark of many psychiatric disorders. The medial extended amygdala, including the medial amygdala and the medial bed nucleus of the stria terminalis, is a key component of functional networks involved in sociality. However, this nuclear complex is highly heterogeneous and contains numerous GABAergic and glutamatergic neuron subpopulations. Deciphering the connections of different neurons is essential in order to understand how this structure regulates different aspects of sociality, and it is necessary to evaluate their differential implication in distinct mental disorders. Developmental studies in different vertebrates are offering new venues to understand neuronal diversity of the medial extended amygdala, and are helping to establish a relation between the embryonic origin and molecular signature of distinct neurons with the functional subcircuits in which they are engaged. These studies have provided many details on the distinct GABAergic neurons of the medial extended amygdala, but information on the glutamatergic neurons is still scarce. Using an Otp-eGFP transgenic mouse and multiple fluorescent labeling, we show that most glutamatergic neurons of the medial extended amygdala originate in a novel telencephalo-opto-hypothalamic embryonic domain (TOH), located at the transition between telencephalon and hypothalamus, which produces Otp-lineage neurons expressing the telencephalic marker Foxg1 but not Nkx2.1 during development. These glutamatergic cells include a subpopulation of projection neurons of the medial amygdala, which activation has been previously shown to promote autistic-like behavior. Our data open new venues for studying the implication of this neuron subtype in neurodevelopmental disorders producing social deficits.

neuroscience↗

bioRxiv2020

Establishment of an African green monkey model for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen candidate vaccines and treatments. Nonhuman primates (NHP) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. Here, we show that African green monkeys support a high level of SARS-CoV-2 replication and develop pronounced respiratory disease that may be more substantial than reported for other NHP species including cynomolgus and rhesus macaques. In addition, SARS-CoV-2 was detected in mucosal samples of all animals including feces of several animals as late as 15 days after virus exposure. Importantly, we show that virus replication and respiratory disease can be produced in African green monkeys using a much lower and more natural dose of SARS-CoV-2 than has been employed in other NHP studies.

microbiology↗