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← One more reason to get a good night’s sleep

The brain uses a quarter of the body's entire energy supply, yet only accounts for about two percent of the body's mass. So how does this unique organ receive and, perhaps more importantly, rid itself of vital nutrients? New research suggests it has to do with sleep.

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Showing Revision 5 created 10/13/2014 by Morton Bast.

  1. Sleep.
  2. It's something we spend about
    a third of our lives doing,
  3. but do any of us really understand what it's all about?
  4. Two thousand years ago, Galen,

  5. one of the most prominent medical researchers
  6. of the ancient world,
  7. proposed that while we're awake,
  8. our brain's motive force, its juice,
  9. would flow out to all the other parts of the body,
  10. animating them but leaving the brain all dried up,
  11. and he thought that when we sleep,
  12. all this moisture that filled the rest of the body
  13. would come rushing back,
  14. rehydrating the brain
  15. and refreshing the mind.
  16. Now, that sounds completely ridiculous to us now,
  17. but Galen was simply trying to explain
  18. something about sleep
  19. that we all deal with every day.
  20. See, we all know based on our own experience
  21. that when you sleep, it clears your mind,
  22. and when you don't sleep,
  23. it leaves your mind murky.
  24. But while we know a great deal more about sleep now
  25. than when Galen was around,
  26. we still haven't understood why it is that sleep,
  27. of all of our activities, has this incredible
  28. restorative function for the mind.
  29. So today I want to tell you about

  30. some recent research
  31. that may shed new light on this question.
  32. We've found that sleep may actually be
  33. a kind of elegant design solution
  34. to some of the brain's most basic needs,
  35. a unique way that the brain
  36. meets the high demands and the narrow margins
  37. that set it apart from all the other organs of the body.
  38. So almost all the biology that we observe

  39. can be thought of as a series of problems
  40. and their corresponding solutions,
  41. and the first problem that every organ must solve
  42. is a continuous supply of nutrients to fuel
  43. all those cells of the body.
  44. In the brain, that is especially critical;
  45. its intense electrical activity uses up
  46. a quarter of the body's entire energy supply,
  47. even though the brain accounts
  48. for only about two percent of the body's mass.
  49. So the circulatory system
  50. solves the nutrient delivery problem
  51. by sending blood vessels to supply nutrients
  52. and oxygen to every corner of our body.
  53. You can actually see it in this video here.

  54. Here, we're imaging blood vessels
  55. in the brain of a living mouse.
  56. The blood vessels form a complex network
  57. that fills the entire brain volume.
  58. They start at the surface of the brain,
  59. and then they dive down into the tissue itself,
  60. and as they spread out, they supply nutrients
  61. and oxygen to each and every cell in the brain.
  62. Now, just as every cell requires

  63. nutrients to fuel it,
  64. every cell also produces waste as a byproduct,
  65. and the clearance of that waste
  66. is the second basic problem
  67. that each organ has to solve.
  68. This diagram shows the body's lymphatic system,
  69. which has evolved to meet this need.
  70. It's a second parallel network of vessels
  71. that extends throughout the body.
  72. It takes up proteins and other waste
  73. from the spaces between the cells,
  74. it collects them, and then dumps them into the blood
  75. so they can be disposed of.
  76. But if you look really closely at this diagram,

  77. you'll see something
  78. that doesn't make a lot of sense.
  79. So if we were to zoom into this guy's head,
  80. one of the things that you would see there
  81. is that there are no lymphatic vessels in the brain.
  82. But that doesn't make a lot of sense, does it?
  83. I mean, the brain is this intensely active organ
  84. that produces a correspondingly
    large amount of waste
  85. that must be efficiently cleared.
  86. And yet, it lacks lymphatic vessels, which means that
  87. the approach that the rest of the body takes
  88. to clearing away its waste
  89. won't work in the brain.
  90. So how, then, does the brain solve

  91. its waste clearance problem?
  92. Well, that seemingly mundane question
  93. is where our group first jumped into this story,
  94. and what we found
  95. as we dove down into the brain,
  96. down among the neurons and the blood vessels,
  97. was that the brain's solution
  98. to the problem of waste clearance,
  99. it was really unexpected.
  100. It was ingenious,
  101. but it was also beautiful.
  102. Let me tell you about what we found.
  103. So the brain has this large pool

  104. of clean, clear fluid called cerebrospinal fluid.
  105. We call it the CSF.
  106. The CSF fills the space that surrounds the brain,
  107. and wastes from inside the brain
  108. make their way out to the CSF,
  109. which gets dumped, along with
    the waste, into the blood.
  110. So in that way, it sounds a lot like
  111. the lymphatic system, doesn't it?
  112. But what's interesting is that the fluid and the waste
  113. from inside the brain,
  114. they don't just percolate their way randomly
  115. out to these pools of CSF.
  116. Instead, there is a specialized network of plumbing
  117. that organizes and facilitates this process.
  118. You can see that in these videos.
  119. Here, we're again imaging into the brain
  120. of living mice.
  121. The frame on your left shows
  122. what's happening at the brain's surface,
  123. and the frame on your right shows
  124. what's happening down below the surface of the brain
  125. within the tissue itself.
  126. We've labeled the blood vessels in red,
  127. and the CSF that's surrounding the brain
  128. will be in green.
  129. Now, what was surprising to us
  130. was that the fluid on the outside of the brain,
  131. it didn't stay on the outside.
  132. Instead, the CSF was pumped back into
  133. and through the brain
  134. along the outsides of the blood vessels,
  135. and as it flushed down into the brain
  136. along the outsides of these vessels,
  137. it was actually helping to clear away,
  138. to clean the waste from the spaces
  139. between the brain's cells.
  140. If you think about it,
  141. using the outsides of these blood vessels like this
  142. is a really clever design solution,
  143. because the brain is enclosed
  144. in a rigid skull
  145. and it's packed full of cells,
  146. so there is no extra space inside it
  147. for a whole second set of vessels
    like the lymphatic system.
  148. Yet the blood vessels,
  149. they extend from the surface of the brain
  150. down to reach every single cell in the brain,
  151. which means that fluid
  152. that's traveling along the outsides of these vessels
  153. can gain easy access to the entire brain's volume,
  154. so it's actually this really clever way
  155. to repurpose one set of vessels, the blood vessels,
  156. to take over and replace the function
  157. of a second set of vessels, the lymphatic vessels,
  158. to make it so you don't need them.
  159. And what's amazing is that no other organ
  160. takes quite this approach
  161. to clearing away the waste from between its cells.
  162. This is a solution that is entirely unique to the brain.
  163. But our most surprising finding

  164. was that all of this,
  165. everything I just told you about,
  166. with all this fluid rushing through the brain,
  167. it's only happening in the sleeping brain.
  168. Here, the video on the left
  169. shows how much of the CSF is moving
  170. through the brain of a living mouse while it's awake.
  171. It's almost nothing.
  172. Yet in the same animal,
  173. if we wait just a little while until it's gone to sleep,
  174. what we see is that the CSF
  175. is rushing through the brain,
  176. and we discovered that at the same time
  177. when the brain goes to sleep,
  178. the brain cells themselves seem to shrink,
  179. opening up spaces in between them,
  180. allowing fluid to rush through
  181. and allowing waste to be cleared out.
  182. So it seems that Galen may actually have been

  183. sort of on the right track when he wrote about
  184. fluid rushing through the brain
  185. when sleep came on.
  186. Our own research, now it's 2,000 years later,
  187. suggests that what's happening is that
  188. when the brain is awake
  189. and is at its most busy,
  190. it puts off clearing away the waste
  191. from the spaces between its cells until later,
  192. and then, when it goes to sleep
  193. and doesn't have to be as busy,
  194. it shifts into a kind of cleaning mode
  195. to clear away the waste
  196. from the spaces between its cells,
  197. the waste that's accumulated throughout the day.
  198. So it's actually a little bit like how you or I,
  199. we put off our household chores during the work week
  200. when we don't have time to get to it,
  201. and then we play catch up on all
    the cleaning that we have to do
  202. when the weekend rolls around.
  203. Now, I've just talked a lot about waste clearance,

  204. but I haven't been very specific
  205. about the kinds of waste
  206. that the brain needs to be clearing
  207. during sleep in order to stay healthy.
  208. The waste product that these recent studies
  209. focused most on is amyloid-beta,
  210. which is a protein that's made
    in the brain all the time.
  211. My brain's making amyloid-beta right now,
  212. and so is yours.
  213. But in patients with Alzheimer's disease,
  214. amyloid-beta builds up and aggregates
  215. in the spaces between the brain's cells,
  216. instead of being cleared away
    like it's supposed to be,
  217. and it's this buildup of amyloid-beta
  218. that's thought to be one of the key steps
  219. in the development of that terrible disease.
  220. So we measured how fast amyloid-beta is cleared
  221. from the brain when it's awake
  222. versus when it's asleep,
  223. and we found that indeed,
  224. the clearance of amyloid-beta
  225. is much more rapid from the sleeping brain.
  226. So if sleep, then,

  227. is part of the brain's solution
  228. to the problem of waste clearance,
  229. then this may dramatically change how we think
  230. about the relationship between sleep,
  231. amyloid-beta, and Alzheimer's disease.
  232. A series of recent clinical studies
  233. suggest that among patients
  234. who haven't yet developed Alzheimer's disease,
  235. worsening sleep quality and sleep duration
  236. are associated with a greater amount
  237. of amyloid-beta building up in the brain,
  238. and while it's important to point out
  239. that these studies don't prove
  240. that lack of sleep or poor sleep
  241. cause Alzheimer's disease,
  242. they do suggest that the failure of the brain
  243. to keep its house clean
  244. by clearing away waste like amyloid-beta
  245. may contribute to the development
  246. of conditions like Alzheimer's.
  247. So what this new research tells us, then,

  248. is that the one thing that all of you
  249. already knew about sleep,
  250. that even Galen understood about sleep,
  251. that it refreshes and clears the mind,
  252. may actually be a big part
  253. of what sleep is all about.
  254. See, you and I, we go to sleep
  255. every single night,
  256. but our brains, they never rest.
  257. While our body is still
  258. and our mind is off walking in dreams somewhere,
  259. the elegant machinery of the brain
  260. is quietly hard at work
  261. cleaning and maintaining
  262. this unimaginably complex machine.
  263. Like our housework,
  264. it's a dirty and a thankless job,
  265. but it's also important.
  266. In your house, if you stop cleaning your kitchen
  267. for a month,
  268. your home will become completely unlivable
  269. very quickly.
  270. But in the brain, the consequences
  271. of falling behind may be much greater
  272. than the embarrassment of dirty countertops,
  273. because when it comes to cleaning the brain,
  274. it is the very health and function
  275. of the mind and the body that's at stake,
  276. which is why understanding these
  277. very basic housekeeping functions of the brain today
  278. may be critical for preventing and treating
  279. diseases of the mind tomorrow.
  280. Thank you.

  281. (Applause)