Neuroscience
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Mitochondrial damage is a central mechanism involved in neurological disorders as Alzheimer's, and Parkinson's diseases and amyotrophic lateral sclerosis. Energy production is the most studied mitochondrial function; however, mitochondria are also involved in processes like calcium buffering homeostasis, and cell death control during apoptosis and necrosis. Using transmission electron microscopy, in this in vivo study in male rats, we describe ultrastructural mitochondrial alterations of spinal motor neurons along chronic AMPA-induced excitotoxicity, which has been described as one of the most relevant mechanisms in ALS disease. ⋯ In addition, by combining the TUNEL assay and immunohistochemistry for mitochondrial enzymes, we show evidence of mitochondrial DNA damage. Evidence of mitochondrial alterations during an AMPA-excitotoxic event is relevant because resembles the mitochondrial alterations previously reported in ALS patients and in transgenic familial ALS models, suggesting that a chronic excitotoxic model can be related to sporadic ALS (as has been shown in recent papers), which represent more than the 90% of the ALS cases. Understanding the mechanisms involved in motor neuron degenerative process, such as the ultrastructural mitochondrial changes permits to design strategies for MN-degeneration treatments in ALS.
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Randomized Controlled Trial
Treadmill walking maintains dual-task gait performance and reduces frontopolar cortex activation in healthy adults.
Studies examining dual-task gait (DTG) have used varying conditions such as overground or treadmill walking, however it is not known whether brain activation patterns differ during these conditions. Therefore, this study compared oxyhaemoglobin (O2Hb) responses of the prefrontal cortex (PFC) during overground and treadmill walking. A total of 30 participants (14M/16F) were recruited in a randomized crossover study comparing overground and treadmill walking under single- and dual-task (STG and DTG) conditions. ⋯ Increased activation was seen in the left and right DLPFC during DTG but did not differ between treadmill and overground walking. Our results support the concept of improved gait efficiency during treadmill walking, indicated by the lack of change in STG and DTG performance and concomitant with a reduction in FPC activation. These findings suggest different neural strategies underpinning treadmill and overground walking, which should be considered when designing gait assessment and rehabilitation interventions.
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Parkinson's Disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons in the nigrostriatal pathway resulting in basal ganglia (BG) dysfunction. This is largely why much of the preclinical and clinical research has focused on pathophysiological changes in these brain areas in PD. The cerebellum is another motor area of the brain. ⋯ D1R expression was higher in PD animals compared to sham animals in both hemispheres in the purkinje cell layer (PCL) and granule cell layer (GCL) of the cerebellar cortex. Interestingly, D2R expression was higher in PD animals than sham animals mostly in the posterior lobe of the PCL, but no discernible pattern of D2R expression was seen in the GCL between PD and sham animals. To our knowledge, we are the first to report these findings, which may lay the foundation for further interrogation of the role of the cerebellum in PD therapy and/or pathophysiology.
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Very recent studies on healthy individuals suggest that changes in the sensibility toward internal bodily sensations across the lifespan affect the ability to mentally represent one's body, in terms of action-oriented and nonaction-oriented body representation (BR). Little is known about the neural correlates of this relation. Here we fill this gap using the neuropsychological model provided by focal brain damage. ⋯ This relation was associated with the disconnection probability of the corticospinal tract, the fronto-insular tract, and the pons. We expand over the previous findings on healthy individuals, supporting the idea that high levels of interoceptive sensibility negatively affect BR. Specific frontal projections and frontal u-shaped tracts may play a pivotal role in such an effect, likely affecting the development of a first-order representation of the self within the brainstem autoregulatory centers and posterior insula and of a second-order representation of the self within the anterior insula and higher-order prefrontal areas.