Dietary RNA Molecules May Hold the Key to Slowing Cellular Aging

 Your competent? doctor is all over healthspan and will guarantee that this research gets done in humans. Oh, you don't trust your doctor to accomplish either point! I wouldn't either. 

healthspan (6 posts to December 2024)

Dietary RNA Molecules May Hold the Key to Slowing Cellular Aging

Summary: Living longer doesn’t always mean living healthier, and researchers are exploring how diet can extend healthspan. A study in worms shows that specific dietary RNA molecules protect cells from harmful protein build-up, a major driver of aging and age-related disease.

These RNAs activate stress responses and autophagy, enhancing resilience and slowing cellular aging across the body. While still early-stage research, the findings suggest diet could play a powerful role in promoting healthier aging in humans too.

Key Facts

• Dietary RNA Benefits: Food-based RNAs reduce harmful protein aggregates.
• Protective Mechanism: They trigger autophagy and stress resilience pathways.
• Whole-Body Impact: Worms lived healthier and more active lives with balanced diets.

Source: University of Basel

People are living longer than ever, but a long life doesn’t necessarily mean a healthy one.

For many, the question isn’t so much “How old do I want to get?” but rather “How do I want to get old?”. While lifespan refers to the years we live from birth to death, “healthspan” describes the number of years we spend in good health.

Healthy aging is also a question of diet. It’s long been known that not just the quantity, but also the individual nutrients impact how we age. Using the tiny worm Caenorhabditis elegans, Spang’s team has now demonstrated that certain RNA molecules in food have a positive effect on the worm’s fitness in old age.

“These molecules prevent the formation of harmful protein aggregates that are typically linked with aging and disease,” says Spang.

The results of their study have been published in “Nature Communications”.

How diet shapes aging

With age, the body becomes less efficient at removing altered and damaged proteins. These can accumulate and form harmful protein aggregates in cells. Such protein aggregates are considered drivers of aging and are associated with multiple age-related diseases including muscular and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

The researchers have discovered that a balanced diet promotes healthspan and specific components in the nematode’s diet exert a protective effect. The worms feed mainly on bacteria that contain double-stranded RNA molecules.

“These dietary RNAs are absorbed in the gut and activate quality-control mechanisms to protect from cellular stress,” explains Emmanouil Kyriakakis, the study’s first author.”

This low-level stress essentially trains the body to cope with protein damage more effectively.”

Diet-dependent mechanisms slow cellular aging

Diet activates autophagy—a cellular “clean-up” process that degrades and recycles damaged proteins. This mechanism reduces harmful protein aggregation and thus slows down cell aging.

“We were surprised to find that the gut communicates with other organs,” says Kyriakakis. “We observed protective effects not only locally, but also in muscles and throughout the whole organism.”

Healthier aging — even in worms
Overall, the worms exposed to a balanced diet were more active and healthier in old age.  “The dietary-RNA species elicit a systemic stress response that protects the worms from protein aggregation during aging,” says Kyriakakis. “thereby extending their healthspan.”

The findings confirm that diet strongly influences health in old age. “Specific food components can stimulate the body’s own protective mechanisms,” adds Spang.

“So, a little stress can be good for you.” Whether individual nutrients can also spark beneficial effects in humans – and potentially help prevent age-related diseases – remains to be investigated. But it’s certainly conceivable. What is clear already: What we eat can shape the way we age.

Key Questions Answered:

Q: What is healthspan, and how does it differ from lifespan?

A: Healthspan refers to the number of years spent in good health, whereas lifespan is simply the total years lived.

Q: How does diet affect aging at the cellular level?

A: Certain dietary RNA molecules help prevent harmful protein aggregates and activate cellular clean-up processes like autophagy.

Q: What did the study on worms reveal about dietary RNA?

A: Worms fed bacterial RNAs showed reduced protein damage, stronger stress defenses, and healthier aging overall.

About this diet, genetics, and aging research news

Author: Angelika Jacobs
Source: University of Basel
Contact: Angelika Jacobs – University of Basel
Image: The image is credited to Neuroscience News

Tiny worm enables scientists to explore the theory that Parkinson's disease starts in the gut

With your chance of Parkinson's post stroke ask your doctor to follow this closely and when an intervention is created to contact you.

Your risk of Parkinsons here:

Parkinson’s Disease May Have Link to Stroke March 2017 

The latest here:

Tiny worm enables scientists to explore the theory that Parkinson's disease starts in the gut

A tiny worm called the C. elegans is enabling scientists to explore the emerging theory that Parkinson's disease starts in the gut.

Key to the condition known to produce uncontrollable shaking, but also characterized by cognitive problems and gastrointestinal distresses like constipation, is a sticky, toxic form of the protein alpha-synuclein, which literally gums up the works of our neurons and kills them.

Although it may seem counterintuitive, there is evidence from science labs like Neuroscientist Danielle Mor's, PhD, that the toxic protein aggregates in the neurons in the gut before it interferes with neurons in the brain. The collection of destructive alpha-synuclein, called Lewy bodies, also has been found on autopsy in neurons embedded in the wall of the gastrointestinal tract of patients with early Parkinson's.

This is now a hot area of research. I think we need to be intervening at the stage of the gut and that is honestly pretty exciting."

Danielle Mor, Faculty Member, Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University

It's known that neurons in the gut regularly communicate with those in the brain and vice versa but just how the alpha-synuclein gets messed up in both is another uncertainty.

Still in animal models, scientists like Mor have watched the sticky wads get spit out of one neuron and get taken up by the next. They've also watched the sticky wads in the gut travel up the spinal cord into the brain. It appears this unfortunate sharing occurs primarily between neurons that already connect and communicate, says Mor.

She just received a two-year $400,000 Early-Investigator Research Award from the U.S. Department of Defense that is helping her learn more about the effects of gut-derived alpha-synuclein on cognition, how it gets inside neurons and whether there are existing drugs that can deter the cognitive impact.

Mor is among the first scientists to look at how alpha-synuclein in the gut affects cognition. And the transparent-throughout-life C. elegans are a great model for pursuing answers, Mor says.

These nematodes, or roundworms, despite their size of about .039 inches, have a gene number and gene pool similar to humans. They also have a digestive tract and many of the same neurotransmitters as humans. Neurotransmitters are chemical messengers that enable neurons to communicate like acetylcholine, associated with memory and learning, and dopamine, which is involved in helping you feel positive emotions like satisfaction and pleasure and helping us plan our movement. Dopamine is known to be substantially depleted in Parkinson's. In fact, a healthy balance between dopamine and acetylcholine is thought to be lost in Parkinson's and to play a major role in the uncontrolled movement that typically characterizes the condition. The death of neurons that produce dopamine is a major focus in Parkinson's research.

Also, like humans the worms have an alimentary nervous system, which is basically a network of neurons in the gut that coordinate functions like digestion and nutrient absorption, and where Mor thinks the early alpha-synuclein first congregates and why she developed her worm models.

"Here we have new models, we are modeling gut-to-brain alpha-synuclein transmission, which we believe is one potential way that this disease occurs in humans and now we will test cognitive function. Now we will test learning and memory in these worms," Mor says.

Previous worm models for Parkinson's have the worms expressing human alpha-synuclein in the neurons in the brain. Mor decided to start by feeding a toxic version of the human protein to the worms. She saw it spread to the brain and the resulting degeneration of dopamine neurons in the worms' brains over just a few days.

"I have seen that it spreads to their different body tissues, and I have seen the neurons degenerating and I have seen the worm have motor problems in a matter of days," Mor says. She notes that a few days is a long time for the worms whose lifespan is just two to four weeks.

Omics eBook

Compilation of the top interviews, articles, and news in the last year.

Download a free copy

For the newly funded studies, she is focusing on the cognitive problems that often surface later in Parkinson's. So as the destructive alpha-synuclein travels from gut to brain she is testing learning and memory in the worms, which she says, again seemingly counterintuitively, is not that tough to do.

"They can learn association between a lot of different things," Mor says. In this case she is focusing on associating a strong, perfumy odor with food. Butanone, a colorless organic compound often used as an industrial solvent, provides the odor and bacteria is a favorite worm food. The C. elegans make the association in about an hour but it's a short-term memory.

"Once they associate that odor with food they move toward that odor," she says. "That is how we give them the quiz." One of the questions she wants to answer is whether feeding the worms the protein aggregate she's watched travel to the brain reduces their association and their scores.

She also wants to better understand how alpha-synuclein gets inside neurons in the gut. There is some evidence, at least in culture, that the toxic protein binds to a sugar coating on the cells, called proteoglycans, which works like a receptor and the alpha-synuclein gets taken up by that unsuspecting neuron.

She's already knocked down a few genes in the pathway that makes the sugar coating, which reduced destruction of dopamine neurons and alleviated some of the disease symptoms in the worms.

"We think we are blocking alpha-synuclein from actually getting into the cells," Mor says, and now her lab is looking more directly at whether that is correct. Right now, they are knocking down 17 genes related to proteoglycans that they suspect as playing a role to begin to identify the ones that actually do.

To speed the identification of drugs that might help and getting that help to people, she is doing high throughput screening of drugs already out there and approved by the Food and Drug Administration. Rather than targeting alpha-synuclein, she wants drugs that will help correct the downstream toxicity of the protein that disrupts normal neuron metabolism and function and ultimately leads to their death.

"We think cellular metabolism is a key feature of how the neurons are dying," Mor says. She notes that others are conducting monoclonal antibody studies against the protein itself, but the results are not yet known.

Her new worm models are complementary to existing mouse models developed with this gut-to-brain approach but unlike these mouse models, her worm model is faster for the large-scale manipulations needed at this juncture to parse the problem, she says.

Although the usual role of alpha-synuclein is not crystal clear, neurons naturally have a lot of the protein, which appears to have an important role in maintaining biological suitcases called vesicles, that in this case help neurons communicate, and neurons do a lot of communicating.

The path of "gut to brain" in Parkinson's is consistent with exposures to environmental toxins in the food or water or in warzones or from other occupational exposures. "We should know if we are endangering ourselves and right now, we don't know," Mor says.

Another possibility is that the gut microbiome, which has important functions like helping regulate metabolism and our immune response in addition to helping digest food, could get out of balance by the food we eat or medicines we take or even stress. The reality is there could be multiple ways alpha-synuclein becomes problematic, she says.

Cognitive decline in patients tends to occur later in Parkinson's and has a high degree of variability. Loss of smell and sleep problems are other symptoms.

Physician Scientist Chandramohan Wakade, MBBS, associate dean of research in the AU College of Allied Health Sciences, and Erhard Bieberich, PhD, biochemist at the University of Kentucky College of Medicine, are mentors for Mor on the new grant.

Source:

Medical College of Georgia at Augusta University

New stroke treatment imitates the survival strategy of C. elegans

I don't expect anything to come out of this, there is NO stroke leadership to ensure human testing gets done and NO stroke strategy to update. If they are right about the 70% adjoining neurons dying then my calculation of 5.4 billion neurons dying my first week is wrong.  I'm going to keep using my 5.4 billion dead neurons the first week because it is shocking and the stroke world needs to be shocked into action, rather than twiddling around with their heads up their asses. But we do need an objective way to calculate brain cell deaths. 

New stroke treatment imitates the survival strategy of C. elegans

Each year, some 200,000 people in Germany and 1 million people in Europe suffer a stroke. This happens when blood clots obstruct major vessels and there is no longer sufficient supply of blood to the brain. If doctors manage to break down or mechanically remove the clot, further damage is prevented.

Nevertheless, 100 percent of the tissue originally affected and about 70 percent of the cells in adjacent areas die off. Scientists based at the LMU Medical Center, the Charité in Berlin and the University of Maryland, Baltimore (USA), led by Dr. Francisco Pan-Montojo (Clinic for Psychiatry and Psychotherapy at University of Munich Hospital) has now been able to demonstrate in several relevant animal models of stroke that glycolic acid can be successfully used to salvage threatened tissue. The experimental treatment imitates a survival strategy of the nematode Caenorhabditis elegans a worm present in the soil, as the researchers report in Advanced Science.

Survival strategies of C. elegans

Related Stories

• Assessing optimal stroke treatment using CTA imaging
• History of adverse pregnancy outcomes may increase odds of midlife stroke
• Tea and coffee consumption associated with lower risk of stroke and dementia

The nematode C. elegans can withstand even desiccation by entering a special larval stage called dauer. Its metabolism stops as the worm dries— and reactivates again on contact with water. Both situations lead to a stress response with a huge increase in the production of reactive molecules (radicals), increased calcium levels in nerve cells, and functional changes in mitochondria, the energy-generating cell organelles. The fact that C. elegans survives this is substantially due to its ability to increase the production of glycolic acid in its cells upon desiccation, as experimental studies have shown: When glycolic acid production is inhibited, then it dies, whereas externally supplied glycolic acid has a protective effect enabling the worms to survive.

Good protection in animal models

In strokes, we see processes similar to those that take place in the desiccation and rehydration of C. elegans."

Dr. Francisco Pan-Montojo, Clinic for Psychiatry and Psychotherapy, University of Munich Hospital

Therefore, the researchers investigated the hypothesis that glycolic acid could be used in mammals to reduce secondary damage resulting from a stroke. Indeed, experiments in various representative in-vitro and animal models of stroke showed that up to 100 percent of all nerve cells could be protected after administration of the molecule. The size of the affected region also decreased. "We were able to demonstrate that the protective effect of glycolic acid is mainly based on counteracting stroke-dependent calcium increases in the cells," explains Pan-Montojo. "Our results indicate that treatment with glycolic acid has the potential to reduce mortality and disability in stroke patients." Together with colleagues, Pan-Montojo has founded a start-up with the aim of advancing the step from research to application in patients.

Source:

Ludwig-Maximilians-Universitaet Muenchen (LMU)

Journal reference:

Chovsepian, A., et al. (2021) A Primeval Mechanism of Tolerance to Desiccation Based on Glycolic Acid Saves Neurons in Mammals from Ischemia by Reducing Intracellular Calcium-Mediated Excitotoxicity. Advanced Science. doi.org/10.1002/advs.202103265.

 

A two-step actin polymerization mechanism drives dendrite branching

 You just might want your doctors and hospital to initiate research in this in higher beings than C. elegans worms. You need dendritic branching for your recovery don't let your doctor and hospital fail you by doing nothing with this.

A two-step actin polymerization mechanism drives dendrite branching

• Rebecca Shi,
• Daniel A. Kramer,
• Baoyu Chen &
• Kang Shen 

Neural Development volume 16, Article number: 3 (2021) Cite this article

• 167 Accesses

• Metrics details

Abstract

Background

Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood.

Methods

We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP.

Results

We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width (“swellings”) give rise to filopodia to facilitate a “rapid growth and pause” mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth.

Conclusions

We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate “swellings” on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor.

Background

Neurite outgrowth and arborization are essential for the establishment and function of neural circuits. In particular, the morphology of dendrites is key for neuronal signal transmission and integration. Dendrite morphogenesis is often guided by extracellular cues recognized through a number of cell surface receptors, such as Semaphorins, DSCAMs, and protocadherins, which in turn instruct activities of various intracellular molecules leading to cytoskeletal reorganization [1, 2]. Similarly, activity-dependent dendritic arbor development also requires cytoskeletal signaling, including through Rho GTPase activity [3] or microtubule stabilization [4].

One major signaling axis for neurite outgrowth is the activation and membrane recruitment of the actin nucleation promotion factor, the WAVE Regulatory Complex (WRC), a pentameric complex comprising Sra1/Cyfip1, Nap1/Hem-2, Abi, HSPC300, and WAVE/Scar [5]. After being activated and recruited by diverse membrane receptors and the Rho family GTPase Rac1, the WRC can then stimulate the Arp2/3 complex to produce branched actin networks [6]. In addition, a distinct actin elongation factor, Ena/VASP, can be recruited downstream of the Netrin receptor, DCC, [7,8,9] to promote polarized filopodia formation during axon guidance. Ena/VASP can also be recruited by the Slit receptor, Robo, to mediate axon repulsion [10, 11]. Interestingly, these distinct actin regulators can act synergistically in several morphological processes. For example, the direct interaction between the WRC and Ena/VASP was shown to play an important role in photoreceptor axon targeting, oogenesis, and macrophage migration in Drosophila, lamellipodia formation during ventral closure of C. elegans embryogenesis, and collective axon extension in mice [12,13,14]. It is, however, largely unknown how the activity of distinct actin regulators is coordinated in complex morphological processes.

One hypothesis is that complex processes like neuronal morphogenesis integrate structurally distinct actin networks built by different actin regulators. For example, in dendritic spines of hippocampal pyramidal neurons, patches of loosely bundled linear actin filaments constitute the dendritic spine neck, whereas branched actin networks drive the expansion of spine heads [15]. Furthermore, Abl tyrosine kinase has been shown to downregulate Ena activity while in parallel activating Rac/WAVE signaling, thus coordinating the balance of linear actin bundles and branched actin networks to regulate Drosophila axon patterning [16]. Finally, branched actin networks generated via the Arp2/3 complex were found to provide sites for initiating new dendrite branches in Drosophila larval sensory da neurons [17]. Therefore, it is likely neurons control morphological changes by dynamically orchestrating the formation of distinct types of actin networks in a coherent manner.

In this work, we provide evidence in support of this hypothesis showing that in the C. elegans PVD neuron, the development of dendritic arbors requires two distinct, but cooperative, steps of actin assembly that involve the WRC, UNC-34 (Ena/VASP), and the actin-binding protein UNC-115 (abLIM). As a recently developed model system for studying dendritic morphogenesis, the PVD neuron elaborates complex dendritic arbors by extending a primary dendrite along the length of the worm, followed by orthogonal secondary, tertiary, and quaternary dendrites, which together create stereotyped “menorah”-like structures [18]. A multipartite ligand-receptor complex, consisting of the extracellular ligands SAX-7, MNR-1, and LECT-2, along with the PVD guidance receptor DMA-1 and its partner HPO-30, directs the growth of PVD dendrites along the epidermis and body wall muscles [19,20,21,22,23]. This ligand-receptor complex recruits actin regulators, including the Rac GEF TIAM-1 and the WRC, through the cytosolic domains of DMA-1 and HPO-30, respectively, which in turn produce F-actin in growing dendrite tips to drive dendrite branching [23,24,25]. However, the mechanisms of F-actin recruitment during distinct morphological steps during dendrite development, such as initiation of new branches and branch elongation, remain unclear.

Here, we show that new dendrite branch points are established first as local “swellings” along dendrites, from which filopodia sprout to enable rapid and efficient outgrowth of dendritic branches. The formation of swellings is mediated by the WRC, while the subsequent extension of filopodial branches is mediated by UNC-34/Ena/VASP and UNC-115/abLIM. Our data suggest that a direct interaction between the WRC and UNC-34 provides the mechanism by which two distinct actin assembling processes are coupled to drive dendrite arborization.

 

A two-step actin polymerization mechanism drives dendrite branching

You might want your doctors and hospital to initiate research in higher animals than roundworms. 

You need dendritic branching to get around white and grey matter dead areas. So ask your doctor  what protocols they have set up for this.

A two-step actin polymerization mechanism drives dendrite branching

• Rebecca Shi,
• Daniel A. Kramer,
• Baoyu Chen &
• Kang Shen 

Neural Development volume 16, Article number: 3 (2021) Cite this article

• 167 Accesses

• Metrics details

Abstract

Background

Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood.

Methods

We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP.

Results

We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width (“swellings”) give rise to filopodia to facilitate a “rapid growth and pause” mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth.

Conclusions

We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate “swellings” on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor.

Background

Neurite outgrowth and arborization are essential for the establishment and function of neural circuits. In particular, the morphology of dendrites is key for neuronal signal transmission and integration. Dendrite morphogenesis is often guided by extracellular cues recognized through a number of cell surface receptors, such as Semaphorins, DSCAMs, and protocadherins, which in turn instruct activities of various intracellular molecules leading to cytoskeletal reorganization [1, 2]. Similarly, activity-dependent dendritic arbor development also requires cytoskeletal signaling, including through Rho GTPase activity [3] or microtubule stabilization [4].

One major signaling axis for neurite outgrowth is the activation and membrane recruitment of the actin nucleation promotion factor, the WAVE Regulatory Complex (WRC), a pentameric complex comprising Sra1/Cyfip1, Nap1/Hem-2, Abi, HSPC300, and WAVE/Scar [5]. After being activated and recruited by diverse membrane receptors and the Rho family GTPase Rac1, the WRC can then stimulate the Arp2/3 complex to produce branched actin networks [6]. In addition, a distinct actin elongation factor, Ena/VASP, can be recruited downstream of the Netrin receptor, DCC, [7,8,9] to promote polarized filopodia formation during axon guidance. Ena/VASP can also be recruited by the Slit receptor, Robo, to mediate axon repulsion [10, 11]. Interestingly, these distinct actin regulators can act synergistically in several morphological processes. For example, the direct interaction between the WRC and Ena/VASP was shown to play an important role in photoreceptor axon targeting, oogenesis, and macrophage migration in Drosophila, lamellipodia formation during ventral closure of C. elegans embryogenesis, and collective axon extension in mice [12,13,14]. It is, however, largely unknown how the activity of distinct actin regulators is coordinated in complex morphological processes.

One hypothesis is that complex processes like neuronal morphogenesis integrate structurally distinct actin networks built by different actin regulators. For example, in dendritic spines of hippocampal pyramidal neurons, patches of loosely bundled linear actin filaments constitute the dendritic spine neck, whereas branched actin networks drive the expansion of spine heads [15]. Furthermore, Abl tyrosine kinase has been shown to downregulate Ena activity while in parallel activating Rac/WAVE signaling, thus coordinating the balance of linear actin bundles and branched actin networks to regulate Drosophila axon patterning [16]. Finally, branched actin networks generated via the Arp2/3 complex were found to provide sites for initiating new dendrite branches in Drosophila larval sensory da neurons [17]. Therefore, it is likely neurons control morphological changes by dynamically orchestrating the formation of distinct types of actin networks in a coherent manner.

In this work, we provide evidence in support of this hypothesis showing that in the C. elegans PVD neuron, the development of dendritic arbors requires two distinct, but cooperative, steps of actin assembly that involve the WRC, UNC-34 (Ena/VASP), and the actin-binding protein UNC-115 (abLIM). As a recently developed model system for studying dendritic morphogenesis, the PVD neuron elaborates complex dendritic arbors by extending a primary dendrite along the length of the worm, followed by orthogonal secondary, tertiary, and quaternary dendrites, which together create stereotyped “menorah”-like structures [18]. A multipartite ligand-receptor complex, consisting of the extracellular ligands SAX-7, MNR-1, and LECT-2, along with the PVD guidance receptor DMA-1 and its partner HPO-30, directs the growth of PVD dendrites along the epidermis and body wall muscles [19,20,21,22,23]. This ligand-receptor complex recruits actin regulators, including the Rac GEF TIAM-1 and the WRC, through the cytosolic domains of DMA-1 and HPO-30, respectively, which in turn produce F-actin in growing dendrite tips to drive dendrite branching [23,24,25]. However, the mechanisms of F-actin recruitment during distinct morphological steps during dendrite development, such as initiation of new branches and branch elongation, remain unclear.

Here, we show that new dendrite branch points are established first as local “swellings” along dendrites, from which filopodia sprout to enable rapid and efficient outgrowth of dendritic branches. The formation of swellings is mediated by the WRC, while the subsequent extension of filopodial branches is mediated by UNC-34/Ena/VASP and UNC-115/abLIM. Our data suggest that a direct interaction between the WRC and UNC-34 provides the mechanism by which two distinct actin assembling processes are coupled to drive dendrite arborization.

Jerusalem Scientists Successfully Produced Genetically Engineered Synapses – A First Step That Could Lead to Repairing Damaged Brains

What leader do we contact to make ABSOLUTELY SURE THIS RESEARCH GETS FOLLOWED UP AND CREATES STROKE PROTOCOLS? Specific names only,  I want someone to take  personal responsibility to get it done.  We have NO LEADERS IN STROKE willing to take any responsibility. I think this is much more likely than stem cells since it could be used to specifically connect problem areas, whereas stem cells are just thrown in there hoping something connects.

Jerusalem Scientists Successfully Produced Genetically Engineered Synapses – A First Step That Could Lead to Repairing Damaged Brains

C. elegans – fortunately referred to in a short version because its C. stands for Caenorhabditis – is a free-living transparent nematodeworm just about one millimeter in length whose home is the soil. It was made famous in 1963 by molecular biologist Sydney Brenner, who suggested that it be researched, primarily in the field of development of the neurons (nerve cells in the brain). Brenner chose the worm because it was more complicated than other well-understood organisms such as bacteria, yet still simple enough to study in depth. He also co-discovered messenger RNA, which is the basis of two effective COVID-19 vaccines.

During the last half-century, the tiny worm has since been extensively used as a model organism for research into human disease and became the first multicellular organism to have its whole genome sequenced, even though it lacked both a circulatory and a respiratory system. C. elegans is still widely used in biology today, with some 15,000 scientific papers published in the past decade that include a reference to the worm.  

Born in South Africa, he moved to the University of Oxford in the United Kingdom and later crossed the Atlantic Ocean to establish the Molecular Sciences Institute in Berkeley, California, and work at the Salk Institute. For this work, he shared the 2002 Nobel Prize in Physiology or Medicine with two other biologists. 

Now, researchers at the Hebrew University of Jerusalem (HUJI) have successfully produced genetically engineered synapses to bypass neural damage – a step that they regard as a first step to what one day could allow scientists to genetically repair damaged brains.

 

Motor Neurons that Multitask

If these multitask with proprioception, I want to know what protocol will bring them back after stroke.
Motor Neurons that Multitask

Summary

Animals use a form of sensory feedback termed proprioception to monitor their body position and modify the motor programs that control movement. In this issue of Neuron, Wen et al. (2012) provide evidence that a subset of motor neurons function as proprioceptors in C. elegans, where B-type motor neurons sense body curvature to control the bending movements that drive forward locomotion.