4th International Conference on Neurology and Brain Disorders

September 09-11, 2021

September 09 -11, 2021 | Virtual Event
INBC 2021

Silvia Lores Arnaiz

Speaker at Neurology and Brain Disorders 2021 - Silvia Lores Arnaiz
University of Buenos Aires , Argentina
Title : Mitochondria and synaptic dysfunction: Implications for aging and brain disorders

Abstract:

Neurons rely almost exclusively on ATP synthesis from the mitochondrial respiratory chain and oxidative phosphorylation to fulfill their energy requirements for neurotransmitter synthesis, release and reuptake. Besides providing energy, mitochondria are also involved in intracellular calcium regulation, cellular redox control and apoptosis. Within the nerve terminals, mitochondria are essential to maintain an adequate synaptic function. Interestingly, neurotransmitter systems can drive mitochondrial dysfunction by different mechanisms including calcium deregulation, oxidative stress or disruption of mitochondrial trafficking and dynamics. In fact, alterations in several neurotransmitter systems -dopaminergic, glutamatergic and cholinergic systems, among others- have been associated with particular changes in mitochondrial functionality during aging and neurodegenerative diseases. Neuronal aging is a complex physiological process, associated to metabolic alterations, mitochondrial dysfunction and free radicals production.

Results from our laboratory have shown that aged mice exhibited a significant reduction in motor performance and walking footprint pattern, and a decrease in acetylcholinesterase activity.

Regarding mitochondrial function, basal respiration and respiration driving proton leak were decreased in synaptosomes from 17-months old mice, while spare respiratory capacity seems to be preserved. Basal mitochondrial membrane potential was maintained in brain cortex synaptosomes from aged mice, whereas a decrease was observed after calcium overload, as compared with young mice. Interestingly, UCP-2 protein expression was increased in synaptosomal samples from 17-month-old mice and superoxide levels were significantly lower than those in young animals. UCP-2 upregulation seems to be a possible mechanism by which synaptic mitochondria would be resistant to suffer oxidative damage. At more advanced ages, regulatory systems may be overwhelmed with the consequent accumulative damage.The use of drugs acting on specific receptors systems are adequate experimental tools to understand the possible interaction between changes at neurotransmitters and mitochondrial function at synapses.

The relationship between mitochondrial dysfunction and neurotransmitter systems such as glutamatergic and cholinergic ones has been extensively studied in aging and brain diseases. However, the involvement of neurotensinergic system in mitochondrial alterations at synapses has not been deeply explored. In our study, levocabastine was used as a neurotensinergic targeted drug, acting as an antagonist of NTS2 receptors. Rat treatment with levocabastine led to important changes in synaptic proteins which are concomitant with altered nitric oxide synthesis. In addition, mitochondrial impairment was evidenced by reduced respiratory control rates, mitochondrial membrane potential depolarization and decreased ATP production rates after levocabastine administration. Mitochondrial bioenergetics impairment may play a role in the functional link between synaptic proteins and nitric oxide synthesis.Understanding the interactions between neurotransmission and mitochondrial dysfunctions is crucial to elucidating the specific mechanisms involved in cognitive decline during normal aging and brain diseases.

Biography:

Academic degrees: Biochemist (1989), Pharmacist (1993), Ph. D. Universidad de Buenos Aires (1994) Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA).

Present position:

  • “Investigador Independiente”, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). At the “Instituto de Bioquímica y Medicina Molecular” Universidad de Buenos Aires (UBA-CONICET). Buenos Aires, Argentina.
  • Full Professor Applied Physical Chemistry (Instituto Universitario del Hospital Italiano, Buenos Aires, Argentina)

Scientific production:

  • More than 50 publications in international scientific journals.
  • Book Editor: “Brain Mitochondria: Distribution and Function”, 2020.

 

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