Long-term space missions pose significant risks of neurodegeneration due to the unique and extreme conditions encountered in space. These conditions include microgravity, radiation exposure, and isolation, which collectively impact the central nervous system (CNS) and can lead to neurodegenerative changes similar to those seen in terrestrial diseases. The effects on astronauts’ mental and physical health are profound, necessitating comprehensive strategies to mitigate these risks.
Microgravity Effect
Microgravity is a condition in which objects and people seem to be weightless or where the force of gravity is minimal. It occurs when there is a negligible amount of gravity or when objects are in free fall.
The microgravity environment presents unique challenges and opportunities for human health
~ Cardiovascular Effects: Prolonged exposure to microgravity leads to Orthostatic Intolerance (a condition that causes symptoms when standing up that are relieved by lying down), Cardiovascular Endothelial Dysfunction (Cardiovascular endothelial dysfunction (ED) is a disease that affects the small blood vessels and impairs blood flow to the heart. It’s a type of non-obstructive coronary artery disease (CAD)), and alterations in gut microbiota, can affect overall astronaut health(Siddiqui et al., 2023)(Peixoto, 2023).
~ Immune System Alterations: The immune response is compromised in microgravity, increasing susceptibility to infections, which poses risks during long missions(Hicks et al., 2023).
- Neurodegenerative Mechanisms:
~ Reactive Oxygen Species (ROS): Microgravity exposure enhances ROS production, contributing to neurodegeneration(Natale et al., 2023).
~ Microglial Activation: Microgravity induces M1 polarization of microglia, leading to increased apoptosis and reduced neuronal viability(Yu et al., 2024).
~ Neural Organoid Studies: Research using neural organoids has shown that microgravity affects cell proliferation and maturation, indicating potential long-term impacts on brain health(Marotta et al., 2023).
~ contributing to neurodegeneration (Natale et al., 2023).
~ Biomarkers: Proteins such as Tau, β-synuclein, and β-amyloid are critical in the neurodegenerative process and serve as potential biomarkers for early diagnosis(Natale et al., 2023).
Radiation Exposure
Radiation exposure in astronauts poses significant risks for neurodegeneration, particularly affecting cognitive functions and increasing the likelihood of cerebrovascular diseases. Research indicates that space radiation can lead to both direct damage to neural tissues and indirect effects through vascular dysfunction, which may contribute to conditions such as dementia and other neurodegenerative diseases. The following sections elaborate on the mechanisms and implications of these effects.
- Mechanisms of Neurodegeneration
~ Cerebrovascular Dysfunction: Ionizing radiation can induce oxidative stress and neuroinflammation, leading to endothelial dysfunction and increased risk of cerebrovascular diseases(Miller et al., 2022)
~ Neurogenesis Impairment: Space radiation negatively impacts hippocampal neurogenesis, crucial for memory and mood regulation, potentially resulting in cognitive decline and mood disorders(McNerlin et al., 2022).
~ Sex Differences: Studies show that male mice exhibit more severe cognitive deficits and neuroinflammation than females following radiation exposure, indicating a need for sex-specific research in astronaut health(Parihar et al., 2020).
- Long-term Health Risks
~ Chronic Neuroinflammation: Heavy ion radiation exposure has been linked to persistent dysfunction in brain regions like the striatum, leading to chronic neuroinflammation and cognitive impairment(Chen et al., 2023)
~ Adverse Outcome Pathways: Research is ongoing to establish pathways linking radiation exposure to neurodegenerative diseases, including Alzheimer’s, highlighting the long-term risks astronauts face(Mi & Norman, 2020).
Molecular mechanisms of neurodegeneration in astronauts
The molecular mechanisms of neurodegeneration in astronauts are significantly influenced by the unique conditions of space, particularly microgravity and ionizing radiation. These factors lead to increased production of reactive oxygen species (ROS), which are implicated in neuronal damage and the onset of neurodegenerative diseases. Understanding these mechanisms is crucial for developing effective monitoring and therapeutic strategies.
Neuropsychiatric Implications
- Depression and Neurodegeneration: The NR2B-PSD-95-nNOS complex (The NR2B-PSD-95-nNOS complex is a molecular signalling assembly critical in neuronal communication and is primarily associated with synaptic plasticity and neurotoxicity mechanisms. The subunits include:
- NR2B (N-Methyl-D-Aspartate Receptor Subunit 2B): This subunit is part of the NMDA receptor, which is crucial for synaptic plasticity and memory formation.
- PSD-95 (Postsynaptic Density Protein 95): A scaffolding protein that organizes signaling complexes at excitatory synapses. PSD-95 links NR2B to nNOS, facilitating the production of nitric oxide (NO) upon NMDA receptor activation
- nNOS (Neuronal Nitric Oxide Synthase): An enzyme that produces nitric oxide, a key signalling molecule involved in various neuronal functions. The activity of nNOS is dependent on its interaction with PSD-95 and is activated by calcium influx through NMDA receptors)
NR2B-PSD-95-nNOS is linked to neuropsychiatric disorders in astronauts, with miR-455-3p showing the potential to regulate this complex to mitigate neuronal damage(Rasheed et al., 2023).
- Astrocyte Function in Neuropsychiatric Disorders: Astrocytes are essential for neuronal development, metabolism, and response to injury, which are critical during the stress of space missions(Zhang et al., 2021). Changes in astrocyte function have been linked to disorders such as schizophrenia, major depressive disorder, and bipolar disorder, all of which could be relevant to astronauts’ mental health(Zhang et al., 2021). Astrocyte dysfunction has been implicated in these symptoms, suggesting that similar mechanisms could affect astronauts’ mental health during missions(Haim & Escartin, 2022).
- Neuropsychiatric Symptoms in Neurodegenerative Diseases: Neurodegenerative diseases often present with neuropsychiatric symptoms like Depression, Anxiety, Sleep disturbances, Mood swings, Cognitive impairments, Interpersonal conflicts, Apathy, or reduced motivation may also manifest in astronauts due to prolonged isolation and stress(Haim & Escartin, 2022).
- Therapeutic Implications: Modulating astrocytic connexins (Connexins are a family of transmembrane proteins that form gap junction channels and hemichannels involved in cell-cell communication. In astrocytes, these proteins play crucial roles in maintaining brain homeostasis, modulating synaptic activity, and responding to injury or diseases. Regulation of functions and expressions said proteins are known as modulating astrocytic connexins) may offer new therapeutic strategies for managing neuropsychiatric symptoms, potentially benefiting astronauts exposed to the unique challenges of space travel(Charvériat et al., 2021).
Implications for Human Exploration
Understanding and addressing space-induced neurodegeneration is essential for the success of long-term missions, such as those to Mars or beyond. As research progresses, it is critical to translate findings from animal models and simulated environments into practical strategies for human astronauts. The future of space exploration depends not only on technological advancements but also on safeguarding the neurological health of those who dare to venture beyond our planet.
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