Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunction. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)—the evolutionarily conserved ortholog of human NTE/PNPLA6—in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism alterations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration pathogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and endoplasmic reticulum interplay.

Glia are crucial for the normal development and functioning of the nervous system in many animals. Insects are widely used for studies of glia genetics and physiology. Drosophila melanogaster surface glia (perineurial and subperineurial) form a blood–brain barrier in the central nervous system and blood–nerve barrier in the peripheral nervous system. Under the subperineurial glia layer, in the cortical region of the central nervous system, cortex glia encapsulate neuronal cell bodies, whilst in the peripheral nervous system, wrapping glia ensheath axons of peripheral nerves. Here, we show that the expression of the evolutionarily conserved swiss cheese gene is important in several types of glia. swiss cheese knockdown in subperineurial glia leads to morphological abnormalities of these cells. We found that the number of subperineurial glia nuclei is reduced under swiss cheese knockdown, possibly due to apoptosis. In addition, the downregulation of swiss cheese in wrapping glia causes a loss of its integrity. We reveal transcriptome changes under swiss cheese knockdown in subperineurial glia and in cortex + wrapping glia and show that the downregulation of swiss cheese in these types of glia provokes reactive oxygen species acceleration. These results are accompanied by a decline in animal mobility measured by the negative geotaxis performance assay.

The gasotransmitter hydrogen sulfide (H₂S) produced by the transsulfuration pathway (TSP) is an important biological mediator, involved in many physiological and pathological processes in multiple higher organisms, including humans. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) enzymes play a central role in H₂S production and metabolism. Here, we investigated the role of H₂S in learning and memory processes by exploring several Drosophila melanogaster strains with single and double deletions of CBS and CSE developed by the CRISPR/Cas9 technique. We monitored the learning and memory parameters of these strains using the mating rejection courtship paradigm and demonstrated that the deletion of the CBS gene, which is expressed predominantly in the central nervous system, and double deletions completely block short- and long-term memory formation in fruit flies. On the other hand, the flies with CSE deletion preserve short- and long-term memory but fail to exhibit long-term memory retention. Transcriptome profiling of the heads of the males from the strains with deletions in Gene Ontology terms revealed a strong down-regulation of many genes involved in learning and memory, reproductive behavior, cognition, and the oxidation–reduction process in all strains with CBS deletion, indicating an important role of the hydrogen sulfide production in these vital processes.

An urgent task of modern medicine is the search for drugs that can stop or slow down the course of neurodegenerative diseases, in particular Alzheimer’s disease. The aim of this work was to determine the effect of fullerenol C₆₀(OH)₃₀ on the pathogenesis of Alzheimer’s disease in the Drosophila melanogaster model. The effect of fullerenol on the life expectancy, the level of geotaxis, learning and memory, and the levels of neurodegeneration and reactive oxygen species in the animal brain was studied. Based on the results, it can be assumed that fullerenol C₆₀(OH)₃₀ is a promising agent for the development of complex therapy for Alzheimer’s disease.

Drosophila melanogaster is one of the most famous insects in biological research. It is widely used to analyse functions of different genes. The phosphatidylcholine lysophospholipase gene swiss cheese was initially shown to be important in the fruit fly nervous system. However, the role of this gene in non-nervous cell types has not been elucidated yet, and the evolutional explanation for the conservation of its function remains elusive. In this study, we analyse expression pattern and some aspects of the role of the swiss cheese gene in the fitness of Drosophila melanogaster. We describe the spatiotemporal expression of swiss cheese throughout the fly development and analyse the survival and productivity of swiss cheese mutants. We found swiss cheese to be expressed in salivary glands, midgut, Malpighian tubes, adipocytes, and male reproductive system. Dysfunction of swiss cheese results in severe pupae and imago lethality and decline of fertility, which is impressive in males. The latter is accompanied with abnormalities of male locomotor activity and courtship behaviour, accumulation of lipid droplets in testis cyst cells and decrease in spermatozoa motility. These results suggest that normal swiss cheese is important for Drosophila melanogaster fitness due to its necessity for both specimen survival and their reproductive success.

Glia is the most common cell type in the central nervous system. Interest in them has increased significantly over the past decades as it has become clear that glia are not just “support” cells for neurons. They also regulate important aspects of the development and functioning of the nervous system. In vertebrates, glial cells perform supporting, trophic, secretory, dividing and protective functions. Despite the fact that the nervous system of Drosophila melanogaster has a simple structure, it is similar in function to mammalian glia. The similarity of glia of Drosophila melanogaster and mammals at the molecular and morphological levels suggests that the study of invertebrate glia will provide a better understanding of the main issues in the development of glia in mammals. Using Drosophila melanogaster makes it possible to study various neuron-glia interactions in an intact organism and the use of a wide range of molecular genetic methods allows us to investigate fundamental questions about the nature of glia. The review presents the classification of glial cells in Drosophila melanogaster, describes the currently known functions of all glial cell types in insects, and compares the functions of various glia types of mammals and Drosophila glial cells. Глиальные клетки (ГК) являются наиболее распространенным типом клеток в центральной нервной системе. Интерес к ним значительно увеличился за последние десятилетия по мере осознания того, что глия является не только «опорными» клетками для нейронов, но также регулирует важные аспекты развития и функционирования нервной системы. У позвоночных ГК выполняют опорную, трофическую, секреторную, разграничительную и защитную функции. Несмотря на то, что нервная система Drosophila melanogaster относительно проста по своей структуре, ей присущи характеристики сложно устроенной глии млекопитающих. Схожесть глии Drosophila melanogaster и млекопитающих на молекулярном и морфологическом уровне дает возможность предположить, что исследование глии беспозвоночных позволит лучше понять основные вопросы развития глии у млекопитающих. Использование Drosophila melanogaster дает возможность изучать различные нейрон-глиальные взаимодействия в интактном организме, а использование широкого набора молекулярно-генетических методов позволяет исследовать фундаментальные вопросы природы глии. В обзоре дана классификация глиальных клеток Drosophila melanogaster, описаны известные на сегодняшний день функции всех типов глии насекомого, а также проведено сравнение функций разных типов глиальных клеток млекопитающих и дрозофилы.