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Steinert, J. R.

Publications and source records attributed to Steinert, J. R..

3 recordsLinked to original sources

High fat diet induces differential age- and gender-dependent changes in neuronal function linked to redox stress.

The prevalence of neurodegenerative diseases, such as Alzheimers disease and Parkinsons disease, is steadily increasing, posing significant challenges to global healthcare systems. Emerging evidence suggests that dietary habits, particularly consumption of high-fat diets specify which fats, may play a pivotal role in the development and progression of neurodegenerative disorders. Moreover, several studies have shed light on the intricate communication between the gut and the brain, known as the gut-brain axis and its involvement in neurodegenerative processes. This study aims to assess the effects of a high-fat dietary intake on various aspects of neuronal function during aging and following gender separation to help understand the potential contributions of diet to neuronal function. To investigate the effects of a high-fat diet, Drosophila melanogaster was used and exposed to standard normal food diet (NF) and high-fat diet (HF). Adults were grouped at 10 and 45 days of age in male and female flies reared under the same conditions. Multiple assays were conducted, showing differential gender- and HF diet-induced oxidative stress levels as determined by malondialdehyde (MDA) measurements, enhanced caspase-3 expression and reduced climbing activity. Adult lifespan under both dietary conditions was unchanged but odour-associated learning ability was reduced in larvae reared in a HF diet. This is the first study to characterise effects of diet on neuronal phenotypes in an age- and gender-specific manner in a Drosophila model. Our findings suggest a HF diet induces differential forms of neuronal dysfunction with age and sex-specific outcomes, characterised by enhanced oxidative stress and cell death which impacts on neuronal and behavioural functions.

neuroscience↗

Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse

Kv3 potassium currents mediate rapid repolarization of action potentials (AP), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal. Deletion of Kv3.3 (but not Kv3.1) increased presynaptic AP duration and facilitated transmitter release, which in turn enhanced short-term depression during high frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 is the presynaptic delayed rectifier, enabling short duration, precisely timed APs to maintain transmission at high frequencies and during sustained synaptic activity.

neuroscience↗

Plum is a novel regulator of synaptic function and muscle size in D. melanogaster

Alterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-{beta} superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), the Drosophila homolog of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction (NMJ), and a negative regulator of body weight and muscle size and function in flies. Here, we identified Plum, a cell surface immunoglobulin homologous to mammalian developmental regulators Protogenin and Nope, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum specifically in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function, likely by de-sequestrating the remaining MYO. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions.

neuroscience↗