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  • 1.
    Brooke-Jones, Megan
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Gáliková, Martina
    Stockholm University, Faculty of Science, Department of Zoology.
    Dircksen, Heinrich
    Stockholm University, Faculty of Science, Department of Zoology.
    Cyanobacterial Neurotoxin Beta-Methyl-Amino-l-Alanine Affects Dopaminergic Neurons in Optic Ganglia and Brain of Daphnia magna2018In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 10, no 12, article id 527Article in journal (Refereed)
    Abstract [en]

    The non-proteinogenic amino acid beta-methyl-amino-l-alanine (BMAA) is a neurotoxin produced by cyanobacteria. BMAA accumulation in the brain of animals via biomagnification along the food web can contribute to the development of neurodegenerative diseases such as Amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC), the latter being associated with a loss of dopaminergic neurons. Daphnia magna is an important microcrustacean zooplankton species that plays a key role in aquatic food webs, and BMAA-producing cyanobacteria often form part of their diet. Here, we tested the effects of BMAA on putative neurodegeneration of newly identified specific dopaminergic neurons in the optic ganglia/brain complex of D. magna using quantitative tyrosine-hydroxylase immunohistochemistry and fluorescence cytometry. The dopaminergic system was analysed in fed and starved isogenic D. magna adults incubated under different BMAA concentrations over 4 days. Increased BMAA concentration showed significant decrease in the stainability of dopaminergic neurons of D. magna, with fed animals showing a more extreme loss. Furthermore, higher BMAA concentrations tended to increase offspring mortality during incubation. These results are indicative of ingested BMAA causing neurodegeneration of dopaminergic neurons in D. magna and adversely affecting reproduction. This may imply similar effects of BMAA on known human neurodegenerative diseases involving dopaminergic neurons.

  • 2.
    Gáliková, Martina
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Dircksen, Heinrich
    Stockholm University, Faculty of Science, Department of Zoology.
    Nässel, Dick R.
    Stockholm University, Faculty of Science, Department of Zoology.
    The thirsty fly: Ion transport peptide (ITP) is a novel endocrine regulator of water homeostasis in Drosophila2018In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 14, no 8, article id e1007618Article in journal (Refereed)
    Abstract [en]

    Animals need to continuously adjust their water metabolism to the internal and external conditions. Homeostasis of body fluids thus requires tight regulation of water intake and excretion, and a balance between ingestion of water and solid food. Here, we investigated how these processes are coordinated in Drosophila melanogaster. We identified the first thirst-promoting and anti-diuretic hormone of Drosophila, encoded by the gene Ion transport peptide (ITP). This endocrine regulator belongs to the CHH (crustacean hyperglycemic hormone) family of peptide hormones. Using genetic gain- and loss-of-function experiments, we show that ITP signaling acts analogous to the human vasopressin and renin-angiotensin systems; expression of ITP is elevated by dehydration of the fly, and the peptide increases thirst while repressing excretion, promoting thus conservation of water resources. ITP responds to both osmotic and desiccation stress, and dysregulation of ITP signaling compromises the fly’s ability to cope with these stressors. In addition to the regulation of thirst and excretion, ITP also suppresses food intake. Altogether, our work identifies ITP as an important endocrine regulator of thirst and excretion, which integrates water homeostasis with feeding of Drosophila.

  • 3.
    Gáliková, Martina
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Klepsatel, Peter
    Obesity and Aging in the Drosophila Model2018In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 7, article id 1896Article, review/survey (Refereed)
    Abstract [en]

    Being overweight increases the risk of many metabolic disorders, but how it affects lifespan is not completely clear. Not all obese people become ill, and the exact mechanism that turns excessive fat storage into a health-threatening state remains unknown. Drosophila melanogaster has served as an excellent model for many diseases, including obesity, diabetes, and hyperglycemia-associated disorders, such as cardiomyopathy or nephropathy. Here, we review the connections between fat storage and aging in different types of fly obesity. Whereas obesity induced by high-fat or high-sugar diet is associated with hyperglycemia, cardiomyopathy, and in some cases, shortening of lifespan, there are also examples in which obesity correlates with longevity. Transgenic lines with downregulations of the insulin/insulin-like growth factor (IIS) and target of rapamycin (TOR) signaling pathways, flies reared under dietary restriction, and even certain longevity selection lines are obese, yet long-lived. The mechanisms that underlie the differential lifespans in distinct types of obesity remain to be elucidated, but fat turnover, inflammatory pathways, and dysregulations of glucose metabolism may play key roles. Altogether, Drosophila is an excellent model to study the physiology of adiposity in both health and disease.

  • 4.
    Gáliková, Martina
    et al.
    Stockholm University, Faculty of Science, Department of Zoology. Max Planck Institute for Biophysical Chemistry, Germany.
    Klepsatel, Peter
    Münch, Judith
    Kühnlein, Ronald P.
    Spastic paraplegia-linked phospholipase PAPLA1 is necessary for development, reproduction, and energy metabolism in Drosophila2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 46516Article in journal (Refereed)
    Abstract [en]

    The human PAPLA1 phospholipase family is associated with hereditary spastic paraplegia (HSP), a neurodegenerative syndrome characterized by progressive spasticity and weakness of the lower limbs. Taking advantage of a new Drosophila PAPLA1 mutant, we describe here novel functions of this phospholipase family in fly development, reproduction, and energy metabolism. Loss of Drosophila PAPLA1 reduces egg hatchability, pre-adult viability, developmental speed, and impairs reproductive functions of both males and females. In addition, our work describes novel metabolic roles of PAPLA1, manifested as decreased food intake, lower energy expenditure, and reduced ATP levels of the mutants. Moreover, PAPLA1 has an important role in the glycogen metabolism, being required for expression of several regulators of carbohydrate metabolism and for glycogen storage. In contrast, global loss of PAPLA1 does not affect fat reserves in adult flies. Interestingly, several of the PAPLA1 phenotypes in fly are reminiscent of symptoms described in some HSP patients, suggesting evolutionary conserved functions of PAPLA1 family in the affected processes. Altogether, this work reveals novel physiological functions of PAPLA1, which are likely evolutionary conserved from flies to humans.

  • 5. Klepsatel, Peter
    et al.
    Nagaraj Girish, Thirnahalli
    Dircksen, Heinrich
    Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
    Gáliková, Martina
    Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology. Slovak Academy of Sciences, Slovakia.
    Reproductive fitness of Drosophila is maximised by optimal developmental temperature2019In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 222, no 10, article id 202184Article in journal (Refereed)
    Abstract [en]

    Whether the character of developmental plasticity is adaptive or non-adaptive has often been a matter of controversy. Although thermal developmental plasticity has been studied in Drosophila for several traits, it is not entirely clear how it affects reproductive fitness. We, therefore, investigated how developmental temperature affects reproductive performance (early fecundity and egg-to-adult viability) of wild-caught Drosophila melanogaster. We have tested competing hypotheses on the character of developmental thermal plasticity using a full factorial design with three developmental and adulthood temperatures within the natural thermal range of this species. To account for potential intraspecific differences, we examined flies from tropical (India) and temperate (Slovakia) climate zones. Our results show that flies from both populations raised at intermediate developmental temperature (25°C) have comparable or higher early fecundity and fertility at all tested adulthood temperatures, while lower (17°C) or higher developmental temperatures (29°C) did not entail any advantage under the tested thermal regimes. Importantly, the superior thermal performance of flies raised at 25°C is apparent even after taking two traits positively associated with reproductive output into account – body size and ovariole number. Thus, in Drosophila melanogaster, development at a given temperature does not necessarily provide any advantage at this thermal environment in terms of reproductive fitness. Our findings strongly support the optimal developmental temperature hypothesis which claims that at different thermal environments the highest fitness is achieved when an organism is raised at its optimal developmental temperature.

  • 6. Klepsatel, Peter
    et al.
    Procházka, Emanuel
    Gáliková, Martina
    Stockholm University, Faculty of Science, Department of Zoology.
    Crowding of Drosophila larvae affects lifespan and other life-history traits via reduced availability of dietary yeast2018In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 110, p. 298-308Article in journal (Refereed)
    Abstract [en]

    Conditions experienced during development have often long-lasting effects persisting into adulthood. In Drosophila, it is well-documented that larval crowding influences fitness-related traits such as body size, starvation resistance and lifespan. However, the underlying mechanism of this phenomenon is not well understood. Here, we show that the effects of increased larval density on life-history traits can be explained by decreased yeast availability in the diet during development. Yeast-poor larval diet alters various life-history traits and mimics the effects of larval crowding. In particular, reduced amount of yeast in larval diet prolongs developmental time, reduces body size, increases body fat content and starvation resistance, and prolongs Drosophila lifespan. Conversely, the effects of larval crowding can be rescued by increasing the concentration of the dietary yeast in the diet during development. Altogether, our results show that the well-known effects of larval crowding on life-history traits are mainly caused by the reduced availability of dietary yeasts due to increased larval competition.

  • 7. Klepsatel, Peter
    et al.
    Wildridge, David
    Gáliková, Martina
    Stockholm University, Faculty of Science, Department of Zoology.
    Temperature induces changes in Drosophila energy stores2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5239Article in journal (Refereed)
    Abstract [en]

    Temperature has a profound impact on animal physiology. In this study, we examined the effect of ambient temperature on the energy stores of the model organism Drosophila melanogaster. By exposing adult males to 11 temperatures between 13 degrees C and 33 degrees C, we found that temperature significantly affects the amount of energy reserves. Whereas flies increase their fat stores at intermediate temperatures, exposure to temperatures below 15 degrees C or above 27 degrees C causes a reduction of fat reserves. Moreover, we found that glycogen stores followed a similar trend, although not so pronounced. To elucidate the underlying mechanism of these changes, we compared the temperature dependence of food consumption and metabolic rate. This analysis revealed that food intake and metabolic rate scale with temperature equally, suggesting that the temperature-induced changes in energy reserves are probably not caused by a mismatch between these two traits. Finally, we assessed the effect of temperature on starvation resistance. We found that starvation survival is a negative exponential function of temperature; however we did not find any clear evidence that implies the relative starvation resistance is compromised at non-optimal temperatures. Our results indicate that whilst optimal temperatures can promote accumulation of energy reserves, exposure to non-optimal temperatures reduces Drosophila energy stores.

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