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Direct neuronal degeneration is brought on by Krabbe disease: study

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Direct neuronal degeneration is brought on by Krabbe disease: study

A recent study found that the gene mutation underlying Krabbe disease directly causes neuronal degeneration, independent of how it affects other cell types. This new mode of action for the mutated gene provides a clearer view of the illness process and could aid in the creation of new treatments.

Galactosylceramidase (GALC) gene mutations are the primary cause of the uncommon autosomal recessive neurological ailment known as Krabbe disease. The lysosomes contain the GALC enzyme, and its lack causes the lipid psychosine to accumulate. Cell membrane instability, degeneration, and cell death are brought on by the buildup of psychosine in the brain and other areas of the body.

One of the main pathological characteristics of Krabbe disease is the loss of myelin insulation around the nerves. Oligodendrocytes, which produce myelin, have naturally been considered to be the disease’s initiators, with the degeneration of neurons acting as a later effect of this myelin loss.

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Other, more recent research has suggested that neurons may be impacted independently, but it has been challenging to test that theory because GALC is widely expressed in the brain and its loss due to disease affects all cell types. To get around this obstacle, the authors developed a mouse model in which GALC expression was only suppressed in neurons while the regular gene was still active elsewhere.

Researchers discovered that psychosine built up in neurons, causing irregularly shaped lysosomes, enlarged axons, and an increase in neuronal mortality, as well as neuroinflammation and deficiencies in mice’s motor function and coordination. No oligodendrocytes were lost, but the absence of neuronal GALC expression did result in a decrease in myelination, perhaps as a result of toxic effects on myelin sheaths from the accumulating psychosine.

For the first time, according to Shin’s findings, galactosylceramidase production in neurons is necessary to preserve and safeguard neuronal function, regardless of how it may affect oligodendrocytes that produce myelin. These findings imply that the lack of the enzyme in neurons may directly contribute to the pathogenesis of Krabbe disease, and that Krabbe disease treatments may require to target the lack of galactosylceramidase production in neurons.

Adding, Shin “Our research is the first effort to specifically examine the neuronal function of the Krabbe disease gene galactosylceramidase in a preclinical live animal model. We discovered an intrinsic neuronal role for this enzyme in creating a neuron-specific mutant of Krabbe disease. This finding suggests that, independent of myelin and other brain cell types, neuronal galactosylceramidase has a primary role in maintaining neuronal homeostasis, and that galactosylceramidase-depleted neurons may be the main cause of Krabbe disease. Galactosylceramidase supplementation to neurons would probably increase the effectiveness of therapeutic approaches for Krabbe illness since the protective role of neuronal galactosylceramidase suggests a new function unrelated to its conventional role in myelination.”

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Train smarter, not harder: How taking occasional breaks from gym can revolutionise your fitness routine

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Train smarter, not harder: How taking occasional breaks from gym can revolutionise your fitness routine

Taking regular breaks from intense training, like deload weeks, helps your body recover, preventing fatigue and injury, and ultimately boosts fitness gains.

When it comes to getting fit, the idea of spending hours at the gym might come to mind, but many fitness experts argue that taking a “deload week” every six to eight weeks is actually key to improving your fitness gains. A deload week involves reducing the intensity of workouts to allow the body to recover from the fatigue and muscle damage caused by intense training.

While high-intensity training helps build strength and fitness, it can also lead to muscle strain, and without adequate recovery, these gains can’t fully materialise. Deload weeks give the body much-needed rest to repair and rebuild, ensuring continued progress. (Also read: Bhagyashree swears by this super easy exercise for instant leg pain relief and better mobility. Watch how to do it )

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Why recovery is key for muscle growth

According to an article by The Conversation, intense exercise can cause tiny tears in muscle fibres, leading to inflammation that requires rest or low-intensity exercise to heal. This inflammation is essential for muscle growth and fitness improvements. However, without proper recovery, muscles remain in a state of slight damage, preventing inflammation from resolving. This chronic state of inflammation can hinder muscle function, reducing oxygen efficiency and impairing performance. Giving muscles time to recover through rest ensures they repair properly and are primed for continued progress, setting us up for greater success in our fitness journey.

Many gymgoers fear taking time off and are worried it will lead to a loss of gains. However, research shows that muscle genes have a “memory imprint,” which keeps them in a semi-prepared state. This allows muscles to respond more quickly and effectively to future training, promoting growth after a rest period. Even after extended periods of reduced intensity, up to seven weeks, muscular fitness can be restored to prime condition—and in some cases, surpass previous levels. Interestingly, recovery can occur twice as fast as it took to reach peak fitness initially, even if some strength is lost.

Taking time off from intense training is crucial to prevent muscle soreness and avoid overtraining syndrome. Overtraining occurs when the body doesn’t get enough rest, leading to prolonged fatigue, decreased performance, and mood disturbances. Symptoms develop gradually, making overtraining difficult to recognize until it’s severe. Rest is essential to avoid these issues and ensure long-term progress in training.

Role of overtraining syndrome and deload weeks

Overtraining syndrome is challenging to quantify due to its vague symptoms. Studies suggest it may affect as few as 10% of elite athletes, though rates could climb to 60% among highly competitive individuals. Recovery is essential for both fitness and overall health. When engaging in heavy gym routines, it’s vital to incorporate sufficient recovery time into your workout plan. Unlike rest days, which involve little to no exercise once or twice a week, deload weeks feature lighter training at reduced intensity—typically about 50% fewer workouts or a 20% drop in workout intensity.

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Both rest days and deload weeks are essential for recovery and crucial to improving fitness. It’s not about choosing one over the other—they complement each other. For instance, intense training for marathons, Ironman, or CrossFit competitions requires weekly rest days alongside scheduled deload weeks. However, for recreational gym-goers exercising 1–3 times weekly at a moderate intensity, the recovery from this routine is often sufficient without the need for additional deload weeks.

Fitness influencers recommend incorporating deload weeks into training schedules every 4–8 weeks, aligning closely with the expert advice of 4–6 weeks. However, it’s crucial to listen to your body and schedule deload weeks as needed. If your performance plateaus or worsens, it may signal time for a deload. Training plans should be flexible enough to allow rest when required. Deload weeks not only enhance performance but also support overall health.

Disclaimer: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.

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