The Fly Blood-Brain Barrier Fights Against Nutritional Stress

Contreras, Esteban G.; Sierralta, Jimena

doi:10.1177/26331055221120252

Cited by 8 publications

(3 citation statements)

References 76 publications

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“…In addition to being hydrophilic and soluble in polar solvents, TMPyP3 can pass through the Drosophila blood–brain barrier (BBB). Drosophila’s BBB is formed of glial cells [ 32 , 33 , 34 ], in contrast to the mammalian, which consists of polarized endothelial cells [ 35 , 36 , 37 ]. From hemolymph, only gases and small lipophilic molecules can cross the fly’s BBB plasma membrane by passive diffusion.…”

Section: Discussionmentioning

confidence: 99%

Systemic Effects of Photoactivated 5,10,15,20-tetrakis(N-methylpyridinium-3-yl) Porphyrin on Healthy Drosophila melanogaster

Filošević Vujnović,

Čabrijan,

Mušković

et al. 2024

BioTech

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Porphyrins are frequently employed in photodynamic therapy (PDT), a non-invasive technique primarily utilized to treat subcutaneous cancers, as photosensitizing agents (PAs). The development of a new PA with improved tissue selectivity and efficacy is crucial for expanding the application of PDT for the management of diverse cancers. We investigated the systemic effects of 5,10,15,20-tetrakis(N-methylpyridinium-3-yl)-porphyrin (TMPyP3) using Drosophila melanogaster adult males. We established the oral administration schedule and demonstrated that TMPyP3 was absorbed and stored higher in neuronal than in non-neuronal extracts. Twenty-four hours after oral TMPyP3 photoactivation, the quantity of hydrogen peroxide (H2O2) increased, but exclusively in the head extracts. Regardless of photoactivation, TMPyP3 resulted in a reduced concentration of H2O2 after 7 days, and this was linked with a decreased capacity to climb, as indicated by negative geotaxis. The findings imply that systemic TMPyP3 therapy may disrupt redox regulation, impairing cellular signaling and behavioral outcomes in the process. To determine the disruptive effect of porphyrins on redox homeostasis, its duration, and the mechanistic variations in retention across various tissues, more research is required.

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Section: Discussionmentioning

confidence: 99%

Systemic Effects of Photoactivated 5,10,15,20-tetrakis(N-methylpyridinium-3-yl) Porphyrin on Healthy Drosophila melanogaster

Filošević Vujnović,

Čabrijan,

Mušković

et al. 2024

BioTech

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“…A blood–brain barrier is found throughout the evolution of complex nervous systems ( Bullock and Horridge, 1965 ). Within invertebrate phyla such as arthropods it has been particularly well studied and closely mirrors the functionality of the vertebrate BBB, both in maintaining homeostasis and responding to disease ( Lane, 1991 ; Carlson et al, 2000 ; Dunton et al, 2021 ; Contreras and Sierralta, 2022 ; Contreras and Klämbt, 2023 ). Moreover, primitive vertebrates as well as invertebrates utilize glial cells to establish the BBB ( Lane, 1991 ; Bundgaard and Abbott, 1992 , 2008 ; Lane and Abbott, 1992 ).…”

Section: Introductionmentioning

confidence: 99%

The Drosophila blood–brain barrier invades the nervous system in a GPCR-dependent manner

Contreras,

Kautzmann,

Klämbt

2024

Front. Cell. Neurosci.

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The blood–brain barrier (BBB) represents a crucial interface between the circulatory system and the brain. In Drosophila melanogaster, the BBB is composed of perineurial and subperineurial glial cells. The perineurial glial cells are small mitotically active cells forming the outermost layer of the nervous system and are engaged in nutrient uptake. The subperineurial glial cells form occluding septate junctions to prevent paracellular diffusion of macromolecules into the nervous system. To address whether the subperineurial glia just form a simple barrier or whether they establish specific contacts with both the perineurial glial cells and inner central nervous system (CNS) cells, we undertook a detailed morphological analysis. Using genetically encoded markers alongside with high-resolution laser scanning confocal microscopy and transmission electron microscopy, we identified thin cell processes extending into the perineurial layer and into the CNS cortex. Interestingly, long cell processes were observed reaching the glia ensheathing the neuropil of the central brain. GFP reconstitution experiments highlighted multiple regions of membrane contacts between subperineurial and ensheathing glia. Furthermore, we identify the G-protein-coupled receptor (GPCR) Moody as negative regulator of the growth of subperineurial cell processes. Loss of moody triggered a massive overgrowth of subperineurial cell processes into the CNS cortex and, moreover, affected the polarized localization of the xenobiotic transporter Mdr65. Finally, we found that GPCR signaling, but not septate junction formation, is responsible for controlling membrane overgrowth. Our findings support the notion that the Drosophila BBB is able to bridge the communication gap between circulation and synaptic regions of the brain by long cell processes.

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“…Functional parallels have also been drawn between the BBBs of vertebrates and D. melanogaster. In both cases, glia allow the transfer of specific support molecules that are required by the underlying neurons while limiting exposure to circulating fluids [21].…”

Section: Introductionmentioning

confidence: 99%

Exploring the molecular makeup of support cells in insect camera eyes

Rathore

Stahl

Benoit

et al. 2023

Preprint

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Animals generally have either compound eyes, which have evolved repeatedly in different invertebrates, or camera eyes, which have evolved many times across the animal kingdom. Both eye types include two important kinds of cells: photoreceptor cells, which can be excited by light, and non-neuronal support cells (SupCs), which provide essential support to photoreceptors. Despite many examples of convergence in eye evolution, similarities in the gross developmental plan and molecular signatures have been discovered, even between phylogenetically distant and functionally different eye types. For this reason, a shared evolutionary origin has been considered for photoreceptors. In contrast, only a handful of studies, primarily on the compound eyes of Drosophila melanogaster, have demonstrated molecular similarities in SupCs. D. melanogaster SupCs (Semper cells and primary pigment cells) are specialized eye glia that share several molecular similarities with certain vertebrate eye glia, including Mueller glia. This led us to speculate whether there are conserved molecular signatures of SupCs, even in functionally different eyes such as the image-forming larval camera eyes of the sunburst diving beetle Thermonectus marmoratus. To investigate this possibility, we used an in-depth comparative whole-tissue transcriptomics approach. Specifically, we dissected the larval principal camera eyes into SupC- and retina-containing regions and generated the respective transcriptomes. Our analysis revealed several conserved features of SupCs including enrichment of genes that are important for glial function (e.g. gap junction proteins such as innexin 3), glycogen production (glycogenin), and energy metabolism (glutamine synthetase 1 and 2). To evaluate the extent of conservation, we compared our transcriptomes with those of fly (Semper cells) and vertebrate (Mueller glia) eye glia as well as respective retinas. T. marmoratus SupCs were found to have distinct genetic overlap with both fly and vertebrate eye glia. These results provide molecular evidence for the deep conservation of SupCs in addition to photoreceptor cells, raising essential questions about the evolutionary origin of eye-specific glia in animals.

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The Fly Blood-Brain Barrier Fights Against Nutritional Stress

Cited by 8 publications

References 76 publications

Systemic Effects of Photoactivated 5,10,15,20-tetrakis(N-methylpyridinium-3-yl) Porphyrin on Healthy Drosophila melanogaster

Systemic Effects of Photoactivated 5,10,15,20-tetrakis(N-methylpyridinium-3-yl) Porphyrin on Healthy Drosophila melanogaster

The Drosophila blood–brain barrier invades the nervous system in a GPCR-dependent manner

Exploring the molecular makeup of support cells in insect camera eyes

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