Introduction: Alzheimer's disease is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while Parkinson's disease is primarily a movement disorder illness having movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. While aging is the main risk factor, epidemiological evidence suggests that the exposure to environmental toxicants, mainly pesticides, metals and solvents could increase the risk of developing neurodegenerative conditions. Oxidative stress in neurodegenerative diseases: Mitochondria function impacts cell respiratory processes, metabolism, energy production, intracellular signaling, free radical production, and apoptosis. In neurodegenerative diseases, mitochondrial dysfunction is associated with a compromised energy production, impaired calcium buffering, activation of proteases and phospholipases, and increased oxidative stress. Oxidative stress induced microglial cells activation, protein aggregation, neuroinflammation and mitochondrial dysfunction lead to neuronal deaths in these disorders. Role of nutrition: Neurodegenerative disease is not curable, but treatment is available to manage the symptoms and slow down the disease progression. The drugs for treating these diseases only reduce the cognitive impairment and behavioral problems, but do not stop the progression of neurodegeneration. Healthy diet, lifestyle improvement and nutraceuticals targeting of oxidative stress, inflammation, abnormal mitochondrial dynamics and the mitochondrial interaction with abnormal diseaserelated proteins and assessment of impact of environmental contaminants including occupational exposures to pesticides, can be a promising approach in the treatment of neurodegenerative diseases. Conclusion: These innovations can be benchmarked on firm understanding of nutrigenomics and the personalized management of individuals at risk.
Summary Instinctive defensive behaviors, consisting of stereotyped sequences of movements and postures, are an essential component of the mouse behavioral repertoire. Since defensive behaviors can be reliably triggered by threatening sensory stimuli, the selection of the most appropriate action depends on the stimulus property. However, since the mouse has a wide repertoire of motor actions, it is not clear which set of movements and postures represent the relevant action. So far, this has been empirically identified as a change in locomotion state. However, the extent to which locomotion alone captures the diversity of defensive behaviors and their sensory specificity is unknown. To tackle this problem, we developed a method to obtain a faithful 3D reconstruction of the mouse body that enabled to quantify a wide variety of motor actions. This higher dimensional description revealed that defensive behaviors are more stimulus specific than indicated by locomotion data. Thus, responses to distinct stimuli that were equivalent in terms of locomotion (e.g., freezing induced by looming and sound) could be discriminated along other dimensions. The enhanced stimulus specificity was explained by a surprising diversity. A clustering analysis revealed that distinct combinations of movements and postures, giving rise to at least 7 different behaviors, were required to account for stimulus specificity. Moreover, each stimulus evoked more than one behavior, revealing a robust one-to-many mapping between sensations and behaviors that was not apparent from locomotion data. Our results indicate that diversity and sensory specificity of mouse defensive behaviors unfold in a higher dimensional space, spanning multiple motor actions.
The ability of specific sensory stimuli to evoke spontaneous behavioural responses in the mouse represents a powerful approach to study how the mammalian brain processes sensory information and selects appropriate motor actions. For visually and auditory guided behaviours the relevant action has been empirically identified as a change in locomotion state. However, the extent to which locomotion alone captures the diversity of those behaviours and their sensory specificity is unknown.To tackle this problem we developed a method to obtain a faithful 3D reconstruction of the mouse body that enabled us to quantify a wide variety of movements and changes in postures. This higher dimensional description of behaviour revealed that responses to different sensory inputs is more stimulus-specific than indicated by locomotion data alone. Thus, equivalent locomotion patterns evoked by different stimuli (e.g. looming and sound evoking locomotion arrest) could be well separated along other dimensions. The enhanced stimulus-specificity was explained by a surprising diversity of behavioural responses. A clustering analysis revealed that distinct combinations of motor actions and postures, giving rise to at least 7 different behaviours, were required to account for stimulus-specificity. Moreover, each stimulus evoked more than one behaviour revealing a robust one-to-many mapping between sensations and behaviours that could not be detected from locomotion data.Our results challenge the current view of visually and auditory guided behaviours as purely locomotion-based actions (e.g. freeze, escape) and indicate that behavioural diversity and sensory specificity unfold in a higher dimensional space spanning multiple motor actions. `
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