Neurotherapeutic effect of Hyptis spp. leaf extracts in Caenorhabditis elegans models of tauopathy and polyglutamine disease: Role of the glutathione redox cycle.

Hyptis suaveolens (HS), Hyptis pectinata (HP) and Hyptis marrubioides (HM) are plants used in folk medicine for treatment of several diseases. Here, we tested the in vivo antioxidant and neuroprotective potential of methanolic extracts from these plants, containing several rosmarinic acid derivatives and isoquercetin. In C. elegans, HS, HP and HM leaf extracts enhanced the antioxidant responses through the induction of specific antioxidant enzymes and demonstrated neurotherapeutic potential in transgenic models of genetically determined human neurodegenerative diseases - Frontotemporal dementia with parkinsonism linked to chromosome 17 and Machado-Joseph disease. Chronic treatment of disease models with HS, HP and HM leaf extracts improved the animals' motor function and increased their tolerance to an oxidative insult. The restorative effect of HM extract in motor performance of both disease models required the presence of glutathione reductase (gsr-1), an enzyme that assures the glutathione redox cycle, highlighting the role of this pathway and unveiling a common candidate therapeutic target for these diseases. Our findings strengthen the relevance of plant-derived bioactive compound discovery for neurodegenerative disorders that remain without effective treatment.

Data on the effects of Hyptis spp. and Lycium spp. plant extracts in C. elegans models of genetically determined neurodegenerative diseases.

Here, we present the data on the biological effects of Hyptis spp. and Lycium spp. plant extracts in Caenorhabditis elegans (C. elegans) models of neurodegenerative diseases, which is related to the work presented in the article "Neurotherapeutic effect of Hyptis spp. leaf extracts in C. elegans models of tauopathy and polyglutamine disease: role of the glutathione redox cycle" [1]. This dataset was generated to define non-toxic concentrations of these plant extracts and to assess their impact on the motor phenotype and oxidative stress resistance of transgenic C. elegans models of two genetically defined neurodegenerative diseases: Machado-Joseph disease and Frontotemporal dementia with Parkinsonism associated to the chromosome 17. The impact of the plant extracts on toxicity was assessed using the food-clearance assay, absorbance being measured daily for seven days at 595 nm to quantify Escherichia coli (E. coli) strain OP50 bacteria consumption. Worm length and motor behaviour, including spontaneous and stimulated movement, were analysed using videos acquired with an Olympus SZX7 stereomicroscope with an integrated camera (Olympus SC30) and processed using the Image J® software and the Wrmtrck plugin. The resistance to oxidative stress induced by 240 µM juglone was assessed by determining the percentage of live animals after 1 hour of exposure.

Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function.

Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corticolimbic circuits, with implications for cognitive processing. We found that the blockade of gliotransmitter release in astrocytes triggers a critical desynchronization of neural theta oscillations between dorsal hippocampus and prefrontal cortex. Moreover, we found a strong cognitive impairment in tasks depending on this network. Importantly, the supplementation with d-serine completely restores hippocampal-prefrontal theta synchronization and rescues the spatial memory and long-term memory of dnSNARE mice. We provide here novel evidence of long distance network modulation by astrocytes, with direct implications to cognitive function.