With an aging population, the topic of neurodegeneration – in its myriad forms – has quickly come to the fore. These are diseases that have diverse symptoms such as memory loss, confusion, and loss of motor function but only reach a common ground in that they are progressive, terminal, and currently have no cure.

Though if you were able to shrink yourself down, Magic School Bus style, and travel into the brains of these affected individuals you may be surprised by what you see. Splashing along the ventricular river, you float about in the lateral ventricles, before scooching through the foramen of Monro, and sloshing through the cerebral aqueduct. Alright. Recess is over. Let’s see what’s going on here!038976160282_1 (1)

You shoot out of the ventricles into intercellular space. Before you, cells loom like whales in a dark ocean. You see glia wrapping themselves around telephone-pole-sized axons that zig and zag in all directions. Dendrites branch and branch in fractal-like perpetuity. Onto the basal ganglia! The cells here are packed close together. You put on special glasses so you can see them communicating with one another (patent pending). Your face is glued to the window. You are looking aghast at the beauty of this intricate system, when you hear Ms. Frizzle (still single, though definitely available) gasp.

“Would you look at that?”

The whole class crams over to one side of the bus. Inside of one of these beautiful, Moby Dick-sized cells you see what looks, for all the world, like a tumbleweed (but those wordy scientists like to refer to them as neur-o-fib-ril-lary tangles). You’re not sure what it’s doing (that’s okay, neither are most researchers!), but it is clear it is not supposed to be there.

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You take the express route out of this patient’s brain, through the Olfactory tract, past dendrites sticking their legs through the epithelium in the nose just to make contact with pinballing particles floating about. This patient has Parkinson’s disease. Maybe this was a one-time thing. He happened to eat some particularly nasty supermarket sushi and got stuck with tumbleweeds in his brain. That’s plausible, right?

Another day, another patient, another field trip. This one with fronto-temporal dementia. This time you take a circuitous and bumpy route up gyri and down sulci, across fissures, decussating, and re-decussating until you reach your destination. This time you gasp. Those beautiful pyramidal cells with their apical dendrites protruding like antennae, and their prominent somas looking like a giant heart, are filled with tumbleweeds. Ms. Fizzle sighs a long unrelated sigh. She has been persistently trying to record a Snapchat to her newest date, however it seems no one has any good ideas on how to record in the frontal lobe.

Day three of this trilogy of field trips. You were promised a roller coaster. Tintinnabulating off the tympanic membrane, you loop-d-loop around the cochlea, hop-scotch across the basilar membranes, corkscrew up tracts, and nose-dive until you come to the main event: that loop within a loop, the hippocampus. Racing along the cell layer in CA3 you hear a screeching sound. The bus is slowing down. It’s not going to make it! You look out the window and there they are again. Those tumbleweeds, infesting everything.

Ms. Fizzle was “out sick” today (read: her date went well) and you have an incredibly overqualified substitute teacher. Dr. Mel Feany of Harvard University. You ask, “Dr. Feany, we’ve been in three brains of three patients with very different diseases, but every time we’ve seen these tumbleweeds. What are they and how are they messing everything up?”

She looks at you with a coy smile and says:

Come to my talk entitled, Genetic Analysis of Neurodegeneration at 4:00PM in CNCB Marilyn Farquhar Seminar Room and I’ll set you straight. For surely, you don’t know the half of it!”

——-

the IT paper to read by Doctor Feany:

“Tau Promotes Neurodegeneration through Global Chromatin Relaxation”

Image Sources:

http://eshop.me100fun.com.hk/the-magic-school-bus-brain-station.html (Magic School Bus)

adaptation of image from: http://www.brightfocus.org/alzheimers/about/understanding/plaques-and-tangles.html

——-

This blog post was brought to you by Sage Aronson, a First-Year Graduate Student in the Neurosciences Program at UCSD. An avid lover of wool socks, things with two wheels, and guacamole — Sage has recently joined the lab of Roberto Malinow and is currently interested in electrophysiology and shining lights into brains.

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