Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes.

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS). When they're not functioning correctly, becoming fragmented and losing their membrane potential, they contribute to these diseases. In this review, we explore how mitochondria fuse and undergo fission, especially in the context of NDs. We discuss the genetic and protein mutations linked to these diseases and how they impact mitochondrial dynamics. We also look at the key regulatory proteins in fusion (MFN1, MFN2, and OPA1) and fission (DRP1 and FIS1), including their post-translational modifications. Furthermore, we highlight potential drugs that can influence mitochondrial dynamics. By unpacking these complex processes, we aim to direct research towards treatments that can improve life quality for people with these challenging conditions.

Proliferation of SH-SY5Y neuroblastoma cells on confined spaces.

BACKGROUND: Microfluidics offers precise drug delivery and continuous monitoring of cell functions, which is crucial for studying the effects of toxins and drugs. Ensuring proper cell growth in these space-constrained systems is essential for obtaining consistent results comparable to standard Petri dishes. NEW METHOD: We investigated the proliferation of SH-SY5Y cells on circular polycarbonate chambers with varying surface areas. SH-SY5Y cells were chosen for their relevance in neurodegenerative disease research. RESULTS: Our study demonstrates a correlation between the chamber surface area and SH-SY5Y cell growth rates. Cells cultured in chambers larger than 10 mm in diameter exhibited growth comparable to standard 60-mm dishes. In contrast, smaller chambers significantly impeded growth, even at identical seeding densities. Similar patterns were observed for HeLaGFP cells, while 16HBE14σ cells proliferated efficiently regardless of chamber size. Additionally, SH-SY5Y cells were studied in a 12-mm diameter sealed chamber to assess growth under restricted gas exchange conditions. COMPARISON WITH EXISTING METHODS: Our findings underscore the limitations of small chamber sizes in microfluidic systems for SH-SY5Y cells, an issue not typically addressed by conventional methods. CONCLUSIONS: SH-SY5Y cell growth is highly sensitive to spatial constraints, with markedly reduced proliferation in chambers smaller than 10 mm. This highlights the need to carefully consider chamber size in microfluidic experiments to achieve cell growth rates comparable to standard culture dishes. The study also shows that while SH-SY5Y and HeLaGFP cells are affected by chamber size, 16HBE14σ cells are not. These insights are vital for designing effective microfluidic systems for bioengineering research.

How Miners and Other Professional Groups Perceive the Benefits and Risks of Hard Coal Mining: A Study on the Role of the Affect Heuristic.

The problems that are inherent in the green shift of the energy sectors are particularly visible in countries where the hard coal mining industry plays an important role in the economy and society. For any transition to be successful, public support is crucial. This empirical study shows that - as a consequence of the affect heuristic - those who perceive hard coal mining as beneficial tend to minimize both its detrimental environmental impacts and its personal safety hazards. Ignoring the affect heuristic may have retarded transformations and led to a failure of many information campaigns.

Unexpected morphological changes within hippocampal structures in a photochemical ring model of cerebral ischaemia.

A photochemical ring model of ischaemia was introduced in the middle of the nineteen eighties. Irradiation by a laser or arc lamp followed by intravenous injection of rose bengal resulted in thrombosis of pial and superficial cortical vessels. This ring model imitated focal ischaemic damage in humans. In our experiment twenty-seven Wistar rats of both sexes weighing 250-300 grams were examined. A photochemical ring model based on irradiation of the area of parietal bone 4 mm posteriorly to the bregma and 4 mm laterally from the sagittal suture was applied. A ring-shaped light beam with a wavelength of 510-540 nm with 5 mm diameter was generated by a high pressure discharge lamp at a power of 400 W. Two groups of rats treated and untreated with MK-801 and two rings of the thickness of 0.35 mm and 0.5 mm were used in the experiment. Morphological examination was performed in animals sacrificed 1 and 4 days after the irradiation. On formalin-fixed and paraffin-embedded slices HE staining method and immunoreaction with antibodies to ubiquitin were applied. Our material confirmed well known information about the dynamics of infarct breakdown, ischaemic-induced angiogenesis, glial reaction and other typical changes described previously in handbooks and numerous papers. In the experiment, morphological changes were more intensive after the irradiation by 0.5 mm than 0.35 mm irradiating rings and 4 days than one day after the irradiation. A surprising finding observed in some of the examined animals was more intensive neuronal damage after treatment with MK-801. Another unpredicted discovery was intensive morphological alterations found in CA4 and CA3 hippocampal sectors. Moreover, these alterations were not limited to the damaged hemisphere, but were also observed contralaterally. In some of the rats, ischaemic and necrotic cells were additionally found within both parasagittal areas. We connect this atypical localization of the ischaemic changes with dispersion of light emitted by the used lamp. Dispersed light also leads to thrombotic occlusion of the meningeal arteries in the parasagittal area. Among these arteries, thrombosis in pericallosal and penetrating arteries was present. Our experiment demonstrated that if a non-laser lamp is used, brain areas distant from the necrotic ring must be carefully investigated.

Standing in Your Peer's Shoes Hurts Your Feats: The Self-Others Discrepancy in Risk Attitude and Impulsivity.

It is often a good strategy to "stand in the other person's shoes" to see a situation from a different perspective. People frequently attempt to infer what someone else would recommend when no advisor is available to help with a decision. Such situations commonly concern intertemporal or risky choices, and the usual assumption is that lay people make such decisions differently than experts do. The aim of our study was to determine what intertemporal and risky decisions people make when they take their own perspective, the perspective of a peer, and the perspectives of an expert or an entrepreneur. In a series of three experiments using a between-subject design, we found that taking the peer's perspective made participants behave more impulsively and more risk aversely in relation to the participants' own perspectives and in relation to their perceptions of experts and entrepreneurs perspectives. Taking an expert's or an entrepreneur's perspective did not change participants' own intertemporal and risky decisions. We explain the findings using the risk as value and the lesser mind theories. Imagining the opponent's perspective in a negotiation as one is advised to do might inadvertently lead to problems because we always see her as more impulsive and more risk averse than she really is. This means that taking a perspective of an expert - not a peer - would be a good way to predict what decisions our opponents make.

Impulsive people have a compulsion for immediate gratification-certain or uncertain.

Impulsivity has been defined as choosing the smaller more immediate reward over a larger more delayed reward. The purpose of this research was to gain a deeper understanding of the mental processes involved in the decision making. We examined participants' rates of delay discounting and probability discounting to determine their correlation with time-probability trade-offs. To establish the time-probability trade-off rate, participants adjusted a risky, immediate payoff to a delayed, certain payoff. In effect, this yielded a probability equivalent of waiting time. We found a strong, positive correlation between delay discount rates and the time-probability trade-offs. This means that impulsive people have a compulsion for immediate gratification, independent of whether the immediate reward is certain or uncertain. Thus, they seem not to be concerned with risk but rather with time.