Alzheimer's Disease Risk and Reward

 

When they hear about my work as a neurodegeneration researcher, people always ask me about Alzheimer's disease risk factors. What really causes Alzheimer's disease?  Plaque and tangle buildup

 

The truth is there's no one secret to staving off dementia, other than living your best life.  This doesn't mean following every impulse, but rather thinking clearly about your habits and consciously making those good habits easier to access.

 

Better lucky than good, but in this case it helps to be both. The kicker is that stress is also a risk factor for Alzheimer's disease and other neurodegenerative diseases, so you'll want to be careful about that too.  Dr. Benton has a refreshing and practical approach about all these thoughts and more.

Deep Brain Degeneration in Alzheimer’s Disease with Dr. Lea Grinberg & Research Team

Losing Control from the Locus Coeruleus, starring Jonathan Chen, Felipe Pereira, and Ian Oh

This episode kicks off a series all about my recent work in neurodegenerative disease, with a an emphasis on Alzheimer’s disease, a devastating and complex dementia and a major focus of my (Dr. Connor Wander’s) dissertation at UNC Chapel Hill.

And where better to start than where the first major pathological changes of tau, a disordered protein that goes dysfunctional in the brain, begins to accumulate and kill neurons.  This ground zero may be in neurons in the deep recesses of the brain act as central regulators of blood flow, inflammation, and neural network dynamics and seem particularly vulnerable to tau in those early, PRe symptomatic stages of Alzheimer’s disease.  I caught up with Dr. Lea Grinberg, Jonathan Chen, Felipe Pereira, and Ian Oh, members of her research team to define the current cutting edge in these studies.

Dr. Lea Grinberg is an Endowed Professor at UCSF with a very active research group focused on early pathological changes in Alzheimer’s disease.  Dr. Grinberg was and is a pioneer in identifying early pathological changes in AD tied to tau aggregation in the locus coeruleus, or LC.

We touched on the network modulatory function of the LC in the most recent episode with Dr. Esteban Oryarzabal. Loss of the LC and other brainstem nuclei is associated with a host of mood and sleep disorders that could be the key to understanding early Alzheimer’s disease.   Check the link below for more from Dr. Grinberg on the links between sleep, Alzheimer’s, and the loss of these brainstem nuclei.  Keep listening for great details on how these studies are conducted, and what’s next on the horizon for research into AD therapeutics and disease processes.

Full show notes at www.sfspodcast.com

This episode is about neural networks on noradrenaline- the key neuromodulator known to flip almost every switch in the brain!  Drs. Esteban Oryarzabal and Connor Wander break down how noradrenaline, or norepinephrine help regulate brain states useful for attention and task-switching.  The studies here cover a whole new way to interpret brain imaging studies, which could have huge implications for neuroscience everywhere!

Youtube link: https://youtu.be/NyMQhw5NpG4

Please note that this episode is special- it's a preview from research that hasn't fully undergone peer review.  This means that the findings discussed are still highly preliminary, and could be subject to change.  That being said, it's an incredible body of work, and fascinating at a minimum!

 

Source Paper: "Chemogenetic Stimulation of Tonic Locus Coeruleus Activity Strengthens the Default Mode Network" https://www.biorxiv.org/content/10.1101/2021.10.28.463794v2

 

From <https://studio.youtube.com/channel/UCbNHbknmBzRb1CQuQ2J1wFA/videos/upload?d=ud&filter=%5B%5D&sort=%7B%22columnType%22%3A%22date%22%2C%22sortOrder%22%3A%22DESCENDING%22%7D>

 

2022 Brings new season for Straight from a Scientist Podcast.  Connor has graduated from UNC Chapel Hill and is now embarking on a scientific industry career, where he explores the biology of aging.  

 

If you missed it over 2020 and 2021, check back for our Science Web Games-- Including two neuroscience games and a Coronavirus explainer: https://www.straightfromascientist.com/science-games/

 

VIDEO WITH VISUAL AIDS ON YOUTUBE!!  

How did you get so put together?  DNA is the blueprint, but it doesn't determine everything.  DNA gets turned into RNA, and then finally into proteins that help build your body and brain.  But there are SO many steps in that process that affect the final product- you.   The sum of these steps is a process called genetic regulation.  Genetic regulation makes sure that not all of our genes are expressed and turned into protein at the same time and same place- that would be a mess!

This episode is all about genetic regulation by long, non-coding RNAs (lncRNAs, pronounced "link-R N A").  LncRNAs are long segments of RNA that serve non-traditional functions in the genome.  Although recently discovered, lncRNAs seem to be involved in everything from the genetic regulation of development to diseases like cancer.  LncRNAs could help rewrite the field of genetic regulation, and might be the biggest shift to understanding genetics since epigenetics became a hot topic.

https://www.straightfromascientist.com/rachel-cherney/

Rachel is also highly involved in other forms of science communication!  Check out the Pipettepen and UNC SWAC for more info!  If you're at UNC, make sure to check TIBBS for career training and opportunities.

  

Specific visual references and their approximate timestamps are listed below.  Make sure to watch the Youtube Video for the full experience!

• 5:00: DNA vs RNA vs Protein - (image in video)
• 7:30: Alternative splicing - (image in video)
• 9:00: Jimena giudice lab at UNC  - http://giudicelab.web.unc.edu/ (Alternative splicing and intracellular trafficking in development and diseases)
• 9:30: It's estimated that >90% of proteins undergo alternative splicing

• 13:30: protein coding gene structure (image in video)
• 15:30: Additional note:  smaller ncRNAs have more defined structure than lncRNAs, their functions are better known
• 17:33: dosage compensation - calico cats (image in video)
• 20:50: An example of a motif that proteins recognize (http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=31097619, figure 3 )
• 21:00: xist repeat structure (https://www.mdpi.com/2311-553X/4/4/28/htm, figure 2, human vs mouse xist)
• 23:00:in cis lncRNA function (https://dev.biologists.org/content/143/21/3882, figure 2 b and c)
• 25:05: Markers are placed on histones, rather than DNA. Histones are proteins that DNA wraps around to compact dna into cells (image in video)
• 25:30: A note: polycomb complexes are conserved to plants and even fungi.  lncRNAs can be found in plants*
• 28:15: immunoprecipitation pipeline (image in video)
• 31:30 -33:35: Examples of Single Nucleotide Polymorphisms (SNPs) (image in video)
• 35:00: Enhancer rnas (https://www.sciencedirect.com/science/article/pii/S1672022917300761 figure 1
• 38:30: single line RNA vs double line DNA, 3DRNA structure (image in video)
• 41:00: xist vs rsx  (http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=31097619, figure 6b )
• 42:30: SWAC /pipettepen,com - link to swac article that prompted this podcast -http://www.thepipettepen.com/what-determines-our-complexity/
• 44:30: TIBBS -https://tibbs.unc.edu/

Marijuana and other cannabis products are becoming increasingly available across the country, and while compounds like CBD have been shown to be safe and even helpful in adults, the side effects of cannabis products are relatively unknown when it comes to the developing fetus.

We've known that alcohol causes birth defects for over 40 years, causing a condition called Fetal Alcohol Syndrome (FAS) and the greater spectrum of Fetal Alcohol Spectrum Disorders (FASD).   But alcohol isn't the only commonly used substance to cause birth defects.   Dr. Parnell's lab and others shows that CBD and THC, the two most well-studied compounds in marijuana can also be harmful to the developing brain.  His research points to a possible fetal cannabis syndrome that could have very similar effects to alcohol.  It seems that both alcohol and mariujana could hit the developing brain at the same stage- but listen in for the details!

 

Neurulation in embryonic development[/caption]

Here's the main publication we discussed.

UNC broke this story late last year here.

This week's episode is about the big things in life- specifically, supermassive black holes in dwarf galaxies!  Connor Wander sits down with Mugdha Polimera from UNC to talk about her work studying supermassive black holes and how their frequency in dwarf (smaller) galaxies can teach us about the formation of the universe.  She quite literally looks back in time!

Mugdha explains how she studies such huge elements so far away, what her studies could mean for our understanding of the universe,  reviews her journey to be an astrophysicist, comments on some popular science myths, and more!  Her research could hold the secrets to how our own galaxy, the milky way, formed eons ago.

https://www.straightfromascientist.com/mugdha-polimera-unc

Here's a great reference for scale, so you can see just how big some of these things are!

Supermassive black hole to scale with giant stars[/caption]

https://neal.fun/size-of-space/

 

Questions about supermassive black holes or dwarf galaxies?  Visit Mugdha's bio to ask about them!

 

 

 

 

 

This episode is all about bad bugs.  Specifically, a flesh-eating bacteria strain called Staphylococcus aureus (S.aureus).  S. aureus is a very common bacteria that's best known for becoming resistant to antibiotics, and becoming MRSA.  Bacteria and the immune system are always at war with each other.  Antibiotics can give the body the edge in this battle, but common resistance is making this much harder in hospitals and homes across the world.  Bacteria survive these antibiotics and the immune system is left to clean up the mess.  Currently, S. aureus is a major cause of death for bacterial infections.

To make things worse, S. aureus and other bacteria can survive more than just antibiotics:  Jenna Beam and the Conlon Lab study how bacteria escape and survive the immune system, and what we can do to stop bacteria in general.  All that and more on this episode!  Make sure to check out the full video on our new Youtube Channel! 

Jenna and the Conlon Lab just published a paper on this very topic!

 

 

 

You can hear more about bacterial resistance mechanisms in general from a recent episode Dr. Brian Conlon did with Curioscity- check it out here.

 

 

 

This weeks episode combines several topics you may have heard of, but never thought about in the same context!  Diabetes and epigenetics are two well-researched topics, but not in the context of fetal development.  During pregnancy, the placenta is the highway that connects a mother and fetus, so when epigenetics act on the placenta, they could have huge effects on development of the fetus and/or the mother.   We break it down straight from a scientist in this episode with Laetitia Myeyruix from UNC's School of Global Public Health, in the Department of Nutrition.  I learned a LOT from this episode, and I'm sure you will too!  Laetitia makes it really easy to understand everything, you don't even need me there!

This is another VIDEO episode!  Check it out on Youtube, and please subscribe to our new channel!

Laetitia is studying the effect of diabetes on epigenetics- the gene access regulators that can ultimately determine which genes go on to be expressed and affect the body.   Laetitia is working with scientists and clinicians in South Africa to determine how diabetes risk in pregnant mothers affects the placenta.

Additionally, we talked about Nutribites, the blog Laetitia edits for-- go check it out for some sweet nutrition advice from the experts!

Also mentioned in the podcast:

Exit West, the book Laetitia mentioned she was reading and highly recommended!

Astrobites 

Oncobites 

And all the other bites blogs!

Joe's Big Idea

The Atlantic Student Subscription

The Economist Student Subscription

 

Join Lebaron (Lee) Agostini and Connor Wander in our FIRST VIDEO episode! This episode is all about Cancer Biology. Lee studies experimental cancer therapies for pancreatic cancer. New cancer therapies called combination or synergystic cancer therapies use multiple drug types to shut down, corner, and eliminate cancer cells in the body.

The full video version of this episode is available on Nov 5th at 7PM EST ! Head on over to our YouTube Channel and check it out there! Also streaming (audio only) on all the usual platforms.

Further information

Here's a recent paper from Lee and his lab at Jefferson University: https://cancerres.aacrjournals.org/content/early/2019/07/04/0008-5472.CAN-18-3645

Any other questions for Lee? Ask him on Instagram or LinkedIn

 

What is Alzheimer's disease? Who can get Alzheimer's, and how does the disease progress?  Maya Gostyla and Connor Wander break down the state of Alzheimer's disease treatments, risk factors, and potential breakthroughs in the field.

 

Related Episodes

If you like this episode, we have tons of podcasts on Alzheimer's disease!

You can hear more about Maya and her research story in this episode.

 

Further Reading about Alzheimer's disease

Here's a great review from the experts on where Alzheimer's research and therapies are today.

For more in-depth analysis of developments in AD and other neurodegenerative diseases, check out Alzforum.org for Alzheimer’s disease background reading.

Read about and see images of protein maps in the human brain that help identify markers of brain disease.

  

Any other questions?  Let us know!  We appreciate your feedback.

You can now support the podcast at https://www.patreon.com/sfspodcast.  Many thanks to our past and present supporters! 

Thanks to Plant Warrior for their support.  Use discount code SFS10 at checkout for 10% off your purchase of plant-based protein.