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Aging is a multifaceted biological process characterized by progressive molecular and cellular damage accumulation. The brain hippocampus undergoes functional deterioration with age, caused by cellular deficits, decreased synaptic communication, and neuronal death, ultimately leading to memory impairment. One of the factors contributing to this dysfunction is the loss of mitochondrial function. In neurons, mitochondria are categorized into synaptic and non-synaptic pools based on their location. Synaptic mitochondria, situated at the synapses, play a crucial role in maintaining neuronal function and synaptic plasticity, whereas non-synaptic mitochondria are distributed throughout other neuronal compartments, supporting overall cellular metabolism and energy supply. The proper function of synaptic mitochondria is essential for synaptic transmission as they provide the energy required and regulate calcium homeostasis at the communication sites between neurons. Maintaining the structure and functionality of synaptic mitochondria involves intricate processes, including mitochondrial dynamics such as fission, fusion, transport, and quality control mechanisms. These processes ensure that mitochondria remain functional, replace damaged organelles, and sustain cellular homeostasis at synapses. Notably, deficiencies in these mechanisms have been increasingly associated with aging and the onset of age-related neurodegenerative diseases. Synaptic mitochondria from the hippocampus are particularly vulnerable to age-related changes, including alterations in morphology and a decline in functionality, which significantly contribute to decreased synaptic activity during aging. This review comprehensively explores the critical roles that mitochondrial dynamics and quality control mechanisms play in preserving synaptic activity and neuronal function. It emphasizes the emerging evidence linking the deterioration of synaptic mitochondria to the aging process and the development of neurodegenerative diseases, highlighting the importance of these organelles from hippocampal neurons as potential therapeutic targets for mitigating cognitive decline and synaptic degeneration associated with aging. The novelty of this review lies in its focus on the unique vulnerability of hippocampal synaptic mitochondria to aging, underscoring their importance in maintaining brain function across the lifespan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Binge drinking is a common pattern of adolescent alcohol consumption characterized by a high alcohol intake within a short period of time; which may seriously affect brain function, triggering in some cases an addictive behavior. Current evidence indicates that alcohol addictive conduct is related to the impairment of the Melanocortin System (MCS). This system participates in the regulation of food intake and promotes anti-inflammatory response in the brain. However, the cellular mechanisms involved in the protective effects induced by MCS against binge-alcohol intoxication are still unknown. Here, we studied the effects of MCS activation on mitochondrial and oxidative damage induced by a binge-like protocol in the hippocampus of adolescent rats. We used a pharmacological activator of MC4R (RO27-3225) and evaluated its effects against oxidative injury, mitochondrial failure, and bioenergetics impairment induced by binge ethanol protocol in the hippocampus of adolescent's rats. Our results indicate that MC4R agonist reduces hippocampal oxidative damage promoting antioxidant (Nrf-2) and mitochondrial biogenesis (PGC1-alpha) pathways in animals subjected to the binge-like protocol. Additionally, MC4R activation prevented mitochondrial potential loss and increased mitochondrial mass that were significantly reduced by binge ethanol protocol. Finally, RO27-3225 treatment increased ATP production and mitochondrial respiratory complex expression in adolescent rats exposed to ethanol. Altogether, these findings show that activation of the MCS pathway through MC4R prevents these negative effects of binge ethanol protocol, suggesting a possible role of the MCS in the reduction of the neurotoxic effects induced by alcohol intoxication in adolescents., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Binge alcohol drinking is a well characterized consumption pattern related with drinking five or more alcoholic beverages during a short period of time followed by a non-drinking period. Several studies showed that this pattern of alcohol intake is becoming very popular among adolescents. However, little is known about the cellular mechanisms involved in ethanol toxicity under these conditions and if these negative changes could be extending to the adulthood. We previously reported that adolescent binge-ethanol consumption impairs brain function acutely. More importantly, we found that animals exposed to this alcohol treatment showed a decrease in the ATP production that remain over time. Therefore, in the present study, we will evaluate the mitochondrial and oxidative alterations that could occur in the adult hippocampus of rats exposed to a unique binge-drinking episode during the adolescence. Our results indicate that adult hippocampus after one adolescent binge-drinking episode presents an increase in the reactive oxygen species production accompanied of mitochondrial dysfunction. Adolescent binge-like ethanol exposure reduced the expression of the mitochondrial respiration complexes, induced mitochondrial depolarization, increased mitochondrial calcium levels, and reduced ATP production in the adult hippocampus. Altogether, our results indicate that adolescence binge alcohol drinking affects the electron transport chain components expression resulting in mitochondrial failure and loss of calcium buffering in the adult hippocampus. Therefore, we reported for first time that adolescent binge-alcohol consumption has severe repercussions on mitochondrial bioenergetics during the adulthood; and that this is not a transitory change until the state of drunkenness disappears as previously believed., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)