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IMBS
International Master Program
in Biomedcal Sciences
.ONAL CONGRESS IN TRANSLATIONAL MEDICINE

UNRAVELING MOLECULAR MECHANISMS INVOLVED IN AFTER-EFFECTS OF ACUTE ETHANOL EXPOSURE IN BRAIN CORTEX. THE DUAL CONTRIBUTION OF MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS IN TRIGGERING APOPTOSIS.   Karadayian Analia, Czerniczyniec Analia,  Lores-Arnaiz Silvia   Instituto de Bioquímica y Medicina Molecular Profesor Alberto Boveris (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires.

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Alcohol is the  most consumed substance around the world together with caffeine and nicotine

3 million deaths every year result from harmful use of alcohol, this represent 5.3 % of all deaths (2018)  85% of adults consume alcohol and 25% reported binge drinking behavior in USA (2018)

os diferentes organismos modelo. Capítulo 4: levaduras – Ecotoxsan

70% of students consume alcohol in an abusive way (2014) 55%  of  students experienced at least one episode of binge drinking within the previous 6 months  Pilatti A et al. 2017  45% of adults consume more alcohol due to Covid pandemic (2020)

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The alcohol hangover refers to the combination of mental and physical symptoms, experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration approaches zero.  (van Schrojenstein Lantman et al., 2016)

ew study reveals your hangover isn&#39;t caused by dehydration

EtOH/SS i.p. Brain cone)
3.8 g/kg BW
6 hsBAC z O
Mitochondrial isolation
Homogenate
600 g 10 min
Supernatant
8000 g 10 min
Pellet
Subcellular
fractions
Synaptosomes
Non-synaptic
mitochondria
Ficoll gradien
3%
13 %

Mitochondrial dysfunction Altered bioenergetics High oxidative stress Reduced antioxidant defenses Alterations in NO metabolism  Impairments of NMDAR/PSD95/nNOS proteins expression

Mild oxidative stress Partial mitochondrial dysfunction

The aim of the present work was to study apoptosis signaling  at the beginning of alcohol hangover  in association with changes in NO metabolism and mitochondrial  bioenergetics

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Resultado de imagen para mouse brain drawing

Calcium influx by glutamate  stimulus b y flow cytometry (FLUO-4AM probe)

Calcium entry is significantly reduced at the beginning of alcohol after-effects. This could affect the activity of NOS and the consequent synthesis of NO.

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2- Mitochondrial permeability and Swelling

Mitochondrial permeability was assayed by the decrease in absorbance at 540 nm

0:04
0:03
0:02
Basal
O Control
Acohol
+ Ca 200 uM

Alcohol after-effects induced increments in mitochondrial permeability indicating the presence of swelling

3- Mitochondrial pro-apoptotic signalling

BAX, BCL-2 and cytochrome c proteins expression was determined by western blot

Pro-apoptotic signals from mitochondria are evidenced at the beginning of alcohol hangover

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Proteins expression was determined by western blot

Caspase 3 & 9 expressions are induced at hangover onset

SIRT-1 expression is decreased at hangover onset

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Intrinsic apoptosis  signaling   are evidenced after acute ethanol exposure in CNS even when ethanol is not longer present  at the systemic  level

The blockage of calcium entry at synapses could explain the previous evidence of a disruption in NO metabolism and NMDAR/PSD-95/ nNOS  pathway

Alterations in calcium homeostasis, mitochondrial dysfunction and oxidative stress can lead to cell death by activation of mitochondrial apoptotic signaling pathways. The decrement in SIRT-1 may impair mitochondrial biogenesis. Stress signals may trigger the increase of p53 which activates apoptosis.

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