Biology subjects

Silva, S. M.

Publications and source records attributed to Silva, S. M..

3 recordsLinked to original sources

bioRxiv2026

Hypothalamic asymmetry in hemisphere-specific neuroendocrine signaling

Brain lesions classically cause contralateral sensorimotor and postural deficits, attributed to the decussation of descending neural pathways. However, recent findings reveal that, beyond neural mechanisms, contralateral effects can also be mediated by the neuroendocrine system via humoral pathways. This raises the possibility that the brain regulates left- and right-sided peripheral processes through hypothalamic neurohormones released into the bloodstream. For such spatially targeted endocrine signaling to occur, hemisphere-specific neural activity must be encoded into side-specific hormonal output--requiring a lateralized organization of hypothalamic neuroendocrine systems. Here, we report molecular asymmetries in the rat hypothalamus that support this mechanism. Transcriptomic analysis revealed asymmetric expression of eleven neurohormonal genes, including Gnrh1, Cck, and Trh, along with distinct left-right side-specific gene co-expression networks. Chemogenetic stimulation of Arg-vasopressin neurons in vasopressin-hM3Dq-mCherry transgenic rats produced generalized changes in these networks--predominantly in the right hypothalamus--suggesting that hypothalamic neurohormonal circuits function as integrated, lateralized ensembles. Stereological analysis revealed asymmetric coordination of vasopressin neurons within the paraventricular nucleus, with the left rostral region decoupled from the right rostral and caudal subregions. Functionally, gonadotropin-releasing hormone, cholecystokinin-8, and thyrotropin-releasing hormone--administered intracisternally in rats with complete spinal cord transection--elicited side-specific peripheral responses, measured as hindlimb postural asymmetry in a binary left-right output model. These neurohormonal effects were therefore transmitted via the humoral route. These findings suggest that multiple hypothalamic neurohormones and their integrated networks are asymmetrically organized, and that their lateralization may be necessary for hemisphere-specific hormonal regulation of peripheral systems.

neuroscience↗

bioRxiv2024

The CryoEM structure of human serum albumin in complex with ligands

Human serum albumin (HSA) is the most prevalent plasma protein in the human body, accounting for 60% of the total plasma protein. HSA plays a major pharmacokinetic function, serving as a facilitator in the distribution of endobiotics and xenobiotics within the organism. In this paper we report the cryoEM structures of HSA in the apo form and in complex with two ligands (salicylic acid and teniposide) at a resolution of 3.5, 3.7 and 3.4 [A], respectively. We expand upon previously published work and further demonstrate that sub-4 [A] maps of [~]60 kDa proteins can be routinely obtained using a 200 kV microscope, employing standard workflows. Most importantly, these maps allowed for the identification of small molecule ligands, emphasizing the practical applicability of this methodology and providing a starting point for subsequent computational modeling and in silico optimization.

biochemistry↗

bioRxiv2024

Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in transwomen

Although the impact of gender-affirming hormone therapy (GAHT) on spermatogenesis in trans women has already been studied, data on its precise effects on the testicular environment is poor. Therefore, this study aimed to characterize, through histological and transcriptomic analysis, the spermatogonial stem cell niche of 106 trans women who underwent standardized GAHT, comprising estrogens and cyproterone acetate. A partial dedifferentiation of Sertoli cells was observed, marked by the co-expression of androgen receptor and anti-Mullerian hormone which mirrors the situation in peripubertal boys. The Leydig cells also exhibited a distribution analogous to peripubertal tissue, accompanied by a reduced insulin-like factor 3 expression. Although most peritubular myoid cells expressed alpha-smooth muscle actin 2, the expression pattern was disturbed. Besides this, fibrosis was particularly evident in the tubular wall and the lumen was collapsing in most participants. A spermatogenic arrest was also observed in all participants. The transcriptomic profile of transgender tissue confirmed a loss of mature characteristics - a partial rejuvenation - of the spermatogonial stem cell niche and, in addition, detected inflammation processes occurring in the samples. The present study shows that GAHT changes the spermatogonial stem cell niche by partially rejuvenating the somatic cells and inducing fibrotic processes. These findings are important to further understand how estrogens and testosterone suppression affect the testis environment, and in the case of orchidectomized testes as medical waste material, their potential use in research.

developmental biology↗