WEBVTT 00:00:01.480 --> 00:00:05.740 For today's episode, we will cover autism and 00:00:05.740 --> 00:00:11.039 Parkinson's. A major region of interest for both 00:00:11.039 --> 00:00:15.380 autism and Parkinson's is the basal ganglia. 00:00:16.940 --> 00:00:20.219 And sticking with this theme, we will cover some 00:00:20.219 --> 00:00:24.559 more basal ganglia, specifically the substantia 00:00:24.559 --> 00:00:29.820 nigra. The substantia nigra is in the midbrain, 00:00:30.100 --> 00:00:34.020 sometimes called the mesencephalon, sometimes 00:00:34.020 --> 00:00:37.759 called the tegmentum, and sometimes referred 00:00:37.759 --> 00:00:41.600 to as a region of the brain stem. Essentially, 00:00:42.219 --> 00:00:45.420 the substantia nigra is towards the top of the 00:00:45.420 --> 00:00:51.020 brain stem. The translation of substantia nigra 00:00:51.020 --> 00:00:57.899 is black substance or black matter. This is because 00:00:57.899 --> 00:01:02.229 of the neuromelanin. Remember neuromelanin's 00:01:02.229 --> 00:01:07.129 roles, and it is black. Because it is black, 00:01:07.469 --> 00:01:13.530 it receives all frequencies of light. Mother 00:01:13.530 --> 00:01:19.329 Nature uses it because it is black. It was selected 00:01:19.329 --> 00:01:25.689 for specific roles. Before I say the roles, this 00:01:25.689 --> 00:01:30.069 is true with the locus coeruleus as well. Same 00:01:30.069 --> 00:01:36.810 area and same black substance. Same cause for 00:01:36.810 --> 00:01:42.510 the black, neuromelanin. Remember the locus coeruleus 00:01:42.510 --> 00:01:46.989 for epinephrine and norepinephrine? You could 00:01:46.989 --> 00:01:51.730 call it brain adrenaline. And that internal calculator 00:01:51.730 --> 00:01:55.290 we covered with the astrocytes, a type of glia 00:01:55.290 --> 00:01:59.319 cell. This internal calculator that we covered 00:01:59.319 --> 00:02:04.280 was calculating effort versus outcome. And if 00:02:04.280 --> 00:02:08.599 the outcome does not match, the glia shuts the 00:02:08.599 --> 00:02:13.819 locus coeruleus off. So melanin, the synthesis 00:02:13.819 --> 00:02:18.800 of melanin comes from tyrosine, an aromatic amino 00:02:18.800 --> 00:02:24.240 acid, those GV light detectors, 200 nanometer 00:02:24.240 --> 00:02:29.330 to 400 nanometer light. and tyrosine peaks at 00:02:29.330 --> 00:02:34.169 280 nanometer, the strongest wavelength that 00:02:34.169 --> 00:02:39.949 arrives on terrestrial land from the sun. 280 00:02:39.949 --> 00:02:45.530 nanometer light starts the UVB range, which is 00:02:45.530 --> 00:02:53.229 280 nanometer to 315. Remember nanometer. There's 00:02:53.229 --> 00:02:58.409 1 ,000 nanometers in one micron. one millimeter. 00:02:59.189 --> 00:03:05.169 And a sheet of paper is 80 to 90 microns, 80 00:03:05.169 --> 00:03:10.770 to 90 millimeters. These are very small and it 00:03:10.770 --> 00:03:14.729 fits the theme because of how small, how upstream 00:03:14.729 --> 00:03:21.069 we are going into our biology. The reason I say 00:03:21.069 --> 00:03:26.400 that is this is upstream. as we can think about 00:03:26.400 --> 00:03:30.960 going, at least for humans and our ability to 00:03:30.960 --> 00:03:35.860 measure and see things. This is quantum biology. 00:03:36.800 --> 00:03:43.479 Environmental signals. How living organisms on 00:03:43.479 --> 00:03:48.939 Earth are created. The sources of energy. How 00:03:48.939 --> 00:03:53.740 cells receive energy. Which provides energy. 00:03:54.090 --> 00:03:58.949 to the living organism. At the atomic level, 00:04:00.009 --> 00:04:03.169 how the powerhouses of the cells, remember the 00:04:03.169 --> 00:04:07.210 mitochondria, how the powerhouses of the cells 00:04:07.210 --> 00:04:13.229 receive the energy, the powers to power the powerhouses. 00:04:14.969 --> 00:04:19.089 Cells respond to environmental signals. Remember 00:04:19.089 --> 00:04:21.870 the two episodes on mitochondria and remember 00:04:21.870 --> 00:04:26.860 the cause of autism episode. Water production 00:04:26.860 --> 00:04:32.740 is coming from cytochrome c -oxidase, and a decrease 00:04:32.740 --> 00:04:37.720 of this water production from the mitochondria 00:04:37.720 --> 00:04:43.019 equals less energy. This is huge for today's 00:04:43.019 --> 00:04:50.660 topic. Autism is underdeveloped cells. Parkinson's 00:04:50.660 --> 00:04:55.660 is that process running in reverse. Cells die 00:04:55.660 --> 00:05:02.519 because they lose energy. Melanin drives transduction. 00:05:04.040 --> 00:05:08.519 A transfer of energy from the environment into 00:05:08.519 --> 00:05:14.899 and through our biology. That's it. That's all 00:05:14.899 --> 00:05:19.579 you need to know about this. That's all you need 00:05:19.579 --> 00:05:25.819 to know about autism. If you can't go here, if 00:05:25.819 --> 00:05:29.180 you don't allow yourself to go here and allow 00:05:29.180 --> 00:05:33.699 yourself to understand this, you won't understand 00:05:33.699 --> 00:05:38.220 anything with our health and life. You will not 00:05:38.220 --> 00:05:44.500 understand autism. You might think that the research 00:05:44.500 --> 00:05:49.319 in autism is pretty lost. It seems like there's 00:05:49.319 --> 00:05:53.480 so much to cover. It seems... Like we're not 00:05:53.480 --> 00:05:58.699 getting anywhere. And this is true. Centralized 00:05:58.699 --> 00:06:04.779 autism research misses this in large part. It 00:06:04.779 --> 00:06:09.540 misses there is no power to the so -called powerhouse 00:06:09.540 --> 00:06:15.240 of the cell. And if you think about an infective 00:06:15.240 --> 00:06:20.000 fix, the treatment for Parkinson's is deep brain 00:06:20.000 --> 00:06:24.750 stimulation. An electrode placed in these areas 00:06:24.750 --> 00:06:30.470 to supplement the loss of energy. Energy lost 00:06:30.470 --> 00:06:35.389 from our modern environments that neglect the 00:06:35.389 --> 00:06:41.009 environment we evolved under. Humans do this 00:06:41.009 --> 00:06:49.050 and no other species will do this. Okay, the 00:06:49.050 --> 00:06:54.959 rose of neuromelanin, this dark, Pigment. It's 00:06:54.959 --> 00:06:58.759 an antioxidant properties. Neuromelanin is our 00:06:58.759 --> 00:07:04.259 greatest defense to environmental toxins. It 00:07:04.259 --> 00:07:09.160 binds metals. This is a huge topic in current 00:07:09.160 --> 00:07:13.860 autism. It's well established. It is well recognized 00:07:13.860 --> 00:07:18.779 and accepted that environmental toxins cause 00:07:18.779 --> 00:07:23.370 autism or increase the risk of autism. But what's 00:07:23.370 --> 00:07:29.550 missing is what's changed. A top topic in autism 00:07:29.550 --> 00:07:34.990 research. It binds to atom and ions and it makes 00:07:34.990 --> 00:07:41.410 it less reactive, less toxic, less harmful. Other 00:07:41.410 --> 00:07:46.649 ways of describing this are binding or sequestering. 00:07:47.879 --> 00:07:53.240 This allows detox of the cells. Thereby, it's 00:07:53.240 --> 00:07:57.740 a neuro protection. A common and a region of 00:07:57.740 --> 00:08:04.199 interest for health is ROS, reactive oxygen species, 00:08:05.079 --> 00:08:10.560 or redox. Okay, so a lot here and we cannot cover 00:08:10.560 --> 00:08:18.069 this. ROS is a very lengthy discussion. But ROS 00:08:18.069 --> 00:08:22.750 can be harmful to mitochondria and cells and 00:08:22.750 --> 00:08:31.129 proteins, lipids, and DNA. Next is free radicals. 00:08:31.209 --> 00:08:34.370 This is of interest. We've covered some free 00:08:34.370 --> 00:08:37.830 radicals when discussing blue light, tech light, 00:08:38.649 --> 00:08:44.269 and or isolated wavelengths of light. The primary 00:08:44.269 --> 00:08:47.450 region of interest here the primary region of 00:08:47.450 --> 00:08:53.169 interest for modern health. Next for melanin 00:08:53.169 --> 00:08:57.929 is a neuronal regulation. Another easy connection, 00:08:58.169 --> 00:09:04.570 especially with dopamine. Also, electrons, the 00:09:04.570 --> 00:09:08.990 energy source from earlier. What powers the powerhouses? 00:09:10.529 --> 00:09:15.129 Remember, cytochrome sea oxidase. Reverse engineer 00:09:15.129 --> 00:09:19.289 the ATP process to the electron transport chain, 00:09:20.009 --> 00:09:22.950 to those cycles pumping out enzymes and ions 00:09:22.950 --> 00:09:26.850 and so forth, all the way back to pyruvate and 00:09:26.850 --> 00:09:31.389 TCA cycle, and uric acid, which is a very hot 00:09:31.389 --> 00:09:36.950 topic in Parkinson's. Just reverse this final 00:09:36.950 --> 00:09:41.009 output of the mitochondria, the ATP, and just 00:09:41.009 --> 00:09:45.100 backtrack, and you can find implications here 00:09:45.100 --> 00:09:48.340 from the loss of environmental signals, from 00:09:48.340 --> 00:09:54.039 the loss of transduction. And remember chromophores. 00:09:54.639 --> 00:09:58.179 The red light chromophores on cytochrome c -oxidase 00:09:58.179 --> 00:10:03.879 and the vitamin D receptors. More and more on 00:10:03.879 --> 00:10:09.659 this light topic. And humanity has seen rapid, 00:10:10.299 --> 00:10:15.470 rapid changes in light. over the past 130 years. 00:10:16.950 --> 00:10:21.889 The question is, what do you think light is? 00:10:24.110 --> 00:10:29.529 Think about it. Are we using the way we evolved 00:10:29.529 --> 00:10:35.649 or have we changed light as a convenience? What 00:10:35.649 --> 00:10:42.750 do you think light is? And is it the same today 00:10:42.750 --> 00:10:49.889 versus evolution of life on earth? This is so 00:10:49.889 --> 00:10:54.470 simple if you understand Dr. Jack Cruz's orange 00:10:54.470 --> 00:11:00.190 tree example. If you block the sun from an orange 00:11:00.190 --> 00:11:03.490 tree, will it produce the same amount of fruit? 00:11:04.049 --> 00:11:08.870 And even if the production of the fruit and also 00:11:09.039 --> 00:11:13.139 for the oranges coming in being bloomed. Will 00:11:13.139 --> 00:11:16.539 those be fully developed or maybe they're not 00:11:16.539 --> 00:11:22.419 fully developed? I use an example of this in 00:11:22.419 --> 00:11:26.940 the episode with Dr. Richard Fry when we discuss 00:11:26.940 --> 00:11:31.259 understanding the roles and sensitivity of mitochondrial 00:11:31.259 --> 00:11:35.779 functioning. And I use this example for describing 00:11:35.779 --> 00:11:40.899 autism and Alzheimer's. There's a short on YouTube 00:11:40.899 --> 00:11:44.480 that you can find if you're interested in this. 00:11:45.779 --> 00:11:51.200 With neuromelanin, with Parkinson's, hypoxia 00:11:51.200 --> 00:11:55.360 of these pigmented neurons break down melanin. 00:11:56.320 --> 00:12:01.000 The source, the power, and the electrons. This 00:12:01.000 --> 00:12:05.899 creates a loss of dopamine. Now, it's common 00:12:05.899 --> 00:12:09.740 that people think Parkinson's is a loss of dopamine, 00:12:09.779 --> 00:12:14.919 and that's true. But research often misses the 00:12:14.919 --> 00:12:18.840 neuromelanin aspect of this, this component of 00:12:18.840 --> 00:12:22.200 this biological energy, these biological concepts. 00:12:23.000 --> 00:12:26.299 So let's go upstream in the biological path. 00:12:28.019 --> 00:12:32.440 The eyes, hair, and skin. This is the starting 00:12:32.440 --> 00:12:36.299 points, the starting lines. Think about this 00:12:36.299 --> 00:12:40.789 in a linear path. If the first domino doesn't 00:12:40.789 --> 00:12:47.350 hit the next, what happens? The eyes, we have 00:12:47.350 --> 00:12:51.009 melanin here. Of course we do, lots of melanin. 00:12:51.649 --> 00:12:56.210 We have melanopsin and we have the retinal pigment 00:12:56.210 --> 00:13:01.870 epithelium or RPE. With this linear path, the 00:13:01.870 --> 00:13:06.190 goal here for this energy transduction is to 00:13:06.190 --> 00:13:10.360 remain efficient. and powerful down the line, 00:13:10.940 --> 00:13:14.899 down the path. To answer the question earlier, 00:13:15.460 --> 00:13:21.320 what is light? Melanin is chosen here because 00:13:21.320 --> 00:13:27.039 it is a dark pigment and absorbs all frequency 00:13:27.039 --> 00:13:32.860 of light. In the summer, if you go outside and 00:13:32.860 --> 00:13:36.110 you wear black versus white, there's going to 00:13:36.110 --> 00:13:38.669 be a big difference, a noticeable difference. 00:13:39.690 --> 00:13:44.110 This is why the pupil is black. This is why Mother 00:13:44.110 --> 00:13:50.129 Nature chose neuromelanin for this role. Melanin 00:13:50.129 --> 00:13:54.190 and the pupil are black to receive the full light 00:13:54.190 --> 00:14:00.110 frequencies. So light is electromagnetic field 00:14:00.110 --> 00:14:06.440 containing a wave and a particle. A photon. A 00:14:06.440 --> 00:14:11.679 wave -particle duality. Waves have the information. 00:14:12.799 --> 00:14:18.240 Photons carry the energy. In the linear example 00:14:18.240 --> 00:14:21.940 of the photon, or photons, hitting the first 00:14:21.940 --> 00:14:27.799 domino, the eye, skin or hair, has to be. It 00:14:27.799 --> 00:14:34.039 must be as much power as possible. to power the 00:14:34.039 --> 00:14:40.220 downstream processes. Biologically, this is how 00:14:40.220 --> 00:14:45.879 we make the dopamine, serotonin, proteins, whatever 00:14:45.879 --> 00:14:49.539 the example like these you want to use. Vitamin 00:14:49.539 --> 00:14:52.879 D is a popular example. Most people understand 00:14:52.879 --> 00:14:57.899 sunlight and vitamin D. You can see the Cause 00:14:57.899 --> 00:15:01.279 of Autism episode for more detail on this and 00:15:01.279 --> 00:15:05.860 also Autism and Gastrointestinal Problems episode. 00:15:06.860 --> 00:15:09.820 There's a lot of this transduction happening 00:15:09.820 --> 00:15:15.620 in the gut. Artificial light versus sunlight 00:15:15.620 --> 00:15:22.259 is the cause. UV light wavelengths keep the melanin 00:15:22.259 --> 00:15:27.879 and dopamine optimized in the midbrain. The Substantia 00:15:27.879 --> 00:15:33.639 Nigra for this Parkinson's discussion. Tyrosine 00:15:33.639 --> 00:15:37.899 is an aromatic amino acid. Remember those UV 00:15:37.899 --> 00:15:43.519 light wavelengths. Do you think artificial light 00:15:43.519 --> 00:15:49.360 is optimizing these biological processes? Don't 00:15:49.360 --> 00:15:53.419 miss the wavelengths throughout the light spectrum. 00:15:54.179 --> 00:15:59.039 This is why I ask, what do you think light is? 00:16:00.720 --> 00:16:05.480 This is also occurring on the skin with melanocytes. 00:16:06.179 --> 00:16:10.340 Something well known in autism research is thyroid 00:16:10.340 --> 00:16:16.299 and the correlation with the risk. Thyroid is 00:16:16.299 --> 00:16:20.679 tyrosine and iodine. Iodine is well established 00:16:20.679 --> 00:16:24.100 in autism as well. This is hitting us right in 00:16:24.100 --> 00:16:28.340 the face. Thyroid in Parkinson's is similar. 00:16:28.820 --> 00:16:33.139 There are strong data here. People with hypothyroidism 00:16:33.139 --> 00:16:37.419 have an increased risk of Parkinson's. Mothers 00:16:37.419 --> 00:16:41.899 with hypothyroidism, their offspring will have 00:16:41.899 --> 00:16:46.440 a higher risk of autism. This is all right here 00:16:46.440 --> 00:16:49.860 in front of us. We have all of these siloed data 00:16:49.860 --> 00:16:53.340 and research studies, but we cannot connect them 00:16:53.340 --> 00:16:56.919 because we don't go upstream. Because research 00:16:56.919 --> 00:17:00.179 has this centralized framework. And it's very 00:17:00.179 --> 00:17:05.519 confusing. Now, in our modern world, the thyroid 00:17:05.519 --> 00:17:10.720 is a pretty frequent lab test because the rates 00:17:10.720 --> 00:17:16.380 of thyroid are increasing. It's pretty common 00:17:16.380 --> 00:17:22.019 to find people, especially adults, with hypothyroidism. 00:17:22.599 --> 00:17:25.759 And we can think about the hypothalamus as the 00:17:25.759 --> 00:17:29.180 control center for the body's hormones. and then 00:17:29.180 --> 00:17:33.079 it communicates to the pituitary. And based off 00:17:33.079 --> 00:17:36.099 of these lab tests, you're probably even familiar 00:17:36.099 --> 00:17:40.880 in your own medical history. You know about T3 00:17:40.880 --> 00:17:49.039 and T4. The 3 and the 4 represents iodine. So 00:17:49.039 --> 00:17:55.920 the T3 is tyrosine, tyroxine, and iodine. If 00:17:55.920 --> 00:18:00.480 you look up autism research, One of the ways 00:18:00.480 --> 00:18:04.380 to mitigate the risk of autism is to supplement 00:18:04.380 --> 00:18:10.740 iodine. Another way that we mitigate risk factors 00:18:10.740 --> 00:18:15.140 for autism are supplementing with things like 00:18:15.140 --> 00:18:19.839 thyroxine, medication. And this is well established 00:18:19.839 --> 00:18:24.519 and it works. It mitigates the risk of autism 00:18:24.519 --> 00:18:29.380 when the mother supplementing with these medications. 00:18:31.559 --> 00:18:37.039 So the important part here is the roles of T3. 00:18:37.599 --> 00:18:42.099 The roles of the thyroid with neuronal function 00:18:42.099 --> 00:18:46.559 and motor function. This is well established, 00:18:46.619 --> 00:18:51.319 but I don't think it's well understood or appreciated. 00:18:52.779 --> 00:18:57.759 So the roles of T3 here. for brain development. 00:18:58.339 --> 00:19:02.400 This is during the fetal development. During 00:19:02.400 --> 00:19:06.380 fetal development and even in through early childhood, 00:19:07.519 --> 00:19:13.240 this T3 is critical for brain growth. It has 00:19:13.240 --> 00:19:17.740 a big influence on cell differentiation and migration. 00:19:18.319 --> 00:19:23.119 Remember the episode on autism and the embryo. 00:19:23.880 --> 00:19:27.880 and the episode covering the placenta. This is 00:19:27.880 --> 00:19:31.299 a key region of interest here. This is going 00:19:31.299 --> 00:19:36.400 to be when autism is developing in the living 00:19:36.400 --> 00:19:40.339 organism. So the T3 with the differentiation 00:19:40.339 --> 00:19:45.279 and migration, autism research has well established 00:19:45.279 --> 00:19:51.740 data on these being a problem in autism. In addition, 00:19:51.980 --> 00:19:57.140 T3's role with maturation of neurons, also another 00:19:57.140 --> 00:20:02.720 well -established data point in autism. Now the 00:20:02.720 --> 00:20:06.980 overarching goal here with this process, building 00:20:06.980 --> 00:20:11.480 the brain development, is for cognitive functions. 00:20:12.400 --> 00:20:15.980 We think about autism, it's underdeveloped, it's 00:20:15.980 --> 00:20:21.150 a neurodevelopmental problem. T3 also helps with 00:20:21.150 --> 00:20:24.869 neuronal activity. So once the cell, the neuron, 00:20:26.029 --> 00:20:31.089 is formed, T3 regulates the gene expression in 00:20:31.089 --> 00:20:35.470 the neuron. And this affects neurotransmitter 00:20:35.470 --> 00:20:39.190 synthesis and receptor expression and synaptic 00:20:39.190 --> 00:20:43.769 plasticity. All of these things are well established 00:20:43.769 --> 00:20:50.990 in the autism data. T3 also acts as a neuro protector 00:20:50.990 --> 00:20:54.829 similar to the neuromelanin and T3 has roles 00:20:54.829 --> 00:20:59.930 with reducing oxidative stress and aiding and 00:20:59.930 --> 00:21:05.869 repair processes after cell injury. T3 has roles 00:21:05.869 --> 00:21:10.029 with metabolism and energy which is well established. 00:21:10.470 --> 00:21:14.690 The lay public likely knows this. However, it's 00:21:14.690 --> 00:21:19.029 the metabolic rate of the neurons. influencing 00:21:19.029 --> 00:21:23.970 the energy availability for the neuronal firing 00:21:23.970 --> 00:21:28.670 and maintaining of the neuronal health, cell 00:21:28.670 --> 00:21:33.009 health. These all have big implications with 00:21:33.009 --> 00:21:37.450 the synaptic transmission as well. And the gene 00:21:37.450 --> 00:21:42.289 expression. So if you're thinking T3 and the 00:21:42.289 --> 00:21:45.250 pituitary and the hypothyroidism, that's all 00:21:45.250 --> 00:21:48.170 associated with hormones. And that's correct. 00:21:48.670 --> 00:21:52.829 T3 acts as a connector, like a node here that's 00:21:52.829 --> 00:21:55.890 connecting the hormones and all of these growth 00:21:55.890 --> 00:21:59.750 factors and the neuronal activity. Now, if you 00:21:59.750 --> 00:22:03.109 go downstream with these implications, it's easier 00:22:03.109 --> 00:22:06.710 for the lay public and just anybody to observe 00:22:06.710 --> 00:22:10.329 these. You might think of them as such as cognitive 00:22:10.329 --> 00:22:13.849 impairments or mood swings, some neurological 00:22:13.849 --> 00:22:17.799 symptoms even. One might go to the doctor and 00:22:17.799 --> 00:22:20.579 say I just haven't been feeling well. My energy 00:22:20.579 --> 00:22:24.740 is low I'm irritable and they will do lab work 00:22:24.740 --> 00:22:28.519 and then well indeed it'll show your TSH might 00:22:28.519 --> 00:22:31.759 be seven or eight or nine or whatever it is and 00:22:31.759 --> 00:22:34.940 then they'll put you on and You might be prescribed 00:22:34.940 --> 00:22:39.440 a couple of micrograms seventy five hundred micrograms 00:22:39.440 --> 00:22:43.019 of this medication Now you can also understand 00:22:43.019 --> 00:22:45.579 the relationship here with the motor functioning 00:22:47.470 --> 00:22:51.569 At the upstream level here, everything's related 00:22:51.569 --> 00:22:56.849 to cell health, the development of cells. If 00:22:56.849 --> 00:23:01.950 we lack energy, the cell lacks energy. So it's 00:23:01.950 --> 00:23:07.069 always coming back to the lack of or the loss 00:23:07.069 --> 00:23:12.150 of energy. For autism, this is happening in the 00:23:12.150 --> 00:23:16.630 womb, early in development, on this linear timeline. 00:23:17.450 --> 00:23:22.210 and we can move this out, stretch the timeline 00:23:22.210 --> 00:23:26.329 across these basal ganglia areas and understand 00:23:26.329 --> 00:23:30.369 the problems here with the efficiency of this 00:23:30.369 --> 00:23:33.990 pathway. Something that's looking at us right 00:23:33.990 --> 00:23:37.769 in the face with this data are the environment 00:23:37.769 --> 00:23:41.569 of the pregnant mother has changed drastically. 00:23:42.430 --> 00:23:46.609 The rates of autism matches the type of environment 00:23:46.960 --> 00:23:50.140 The mothers are in, and it's not a direct shot 00:23:50.140 --> 00:23:53.339 at the mother. It's just the modern world, the 00:23:53.339 --> 00:23:57.839 modern environment. We are losing energy to the 00:23:57.839 --> 00:24:01.160 environment. Now, if you talk to a researcher 00:24:01.160 --> 00:24:04.180 on mitochondria, they might think, yeah, it's 00:24:04.180 --> 00:24:06.900 a mitochondrial dysfunction, but they might not 00:24:06.900 --> 00:24:09.960 know why. And that's not a shot against them 00:24:09.960 --> 00:24:14.019 either. It's just the centralized framework that 00:24:14.019 --> 00:24:17.329 determines which lens. Are we looking through? 00:24:17.750 --> 00:24:20.190 What are we looking at? What are we looking for? 00:24:21.009 --> 00:24:24.589 It's very siloed. It's very narrow. It almost 00:24:24.589 --> 00:24:29.609 lacks depth, if I had to sum it up. Now, remember 00:24:29.609 --> 00:24:35.049 thyroid, row, and the biosynthesis of tyrosine 00:24:35.049 --> 00:24:38.910 here as well. I cannot harp on this enough. Remember 00:24:38.910 --> 00:24:44.369 the biosynthesis of tyrosine making thyroxine 00:24:44.369 --> 00:24:49.089 and making L -Dopa which is common with the Parkinson's 00:24:49.089 --> 00:24:53.230 theme and making dopamine and epinephrine and 00:24:53.230 --> 00:24:57.910 norepinephrine and melanin. Melanin is the missing 00:24:57.910 --> 00:25:02.890 role here. It's the underrated role. Remember 00:25:02.890 --> 00:25:06.670 melanin's role with water. So the mitochondria 00:25:06.670 --> 00:25:10.430 is here once again and the regions with this 00:25:10.430 --> 00:25:13.750 most neuromelanin are centered in the midbrain. 00:25:13.759 --> 00:25:17.299 areas that contains lots of other water in the 00:25:17.299 --> 00:25:22.960 brain. The melanin -water interaction equals 00:25:22.960 --> 00:25:28.700 more electrons. Remember, light changes the physics 00:25:28.700 --> 00:25:34.400 of water. This is what it is all about. Electrons 00:25:34.400 --> 00:25:38.079 and the environmental signals. And remember the 00:25:38.079 --> 00:25:42.000 water being produced out of mitochondria. As 00:25:42.000 --> 00:25:47.099 we age, Roughly each decade of life, we lose 00:25:47.099 --> 00:25:51.960 roughly 10 % of the water being produced in mitochondria. 00:25:52.240 --> 00:25:56.779 And this occurs across the lifespan. 10 % roughly 00:25:56.779 --> 00:26:01.200 every 10 years. So we are losing energy naturally. 00:26:01.920 --> 00:26:04.900 This is entropy. This is senescence. This is 00:26:04.900 --> 00:26:10.519 life, aging and life. Check this with heteroplasmy. 00:26:10.920 --> 00:26:14.339 If you want to... good marker, a good biological 00:26:14.339 --> 00:26:20.460 marker. Look into heteroplasmy. Now, with disease 00:26:20.460 --> 00:26:24.819 and other insults and such, we can lose more 00:26:24.819 --> 00:26:28.640 frequency of water. This rate can be increased. 00:26:29.819 --> 00:26:33.140 Now you can even begin to understand the other 00:26:33.140 --> 00:26:37.579 neurodegenerative problems and why the rates 00:26:37.579 --> 00:26:42.869 of these are increasing. Okay. I said in a previous 00:26:42.869 --> 00:26:45.390 episode because we're covering the basal ganglia 00:26:45.390 --> 00:26:48.869 quite extensively here. I would cover the direct 00:26:48.869 --> 00:26:52.269 pathway and the indirect pathway in the basal 00:26:52.269 --> 00:26:57.690 ganglia. So I'll do that now. Quick recap on 00:26:57.690 --> 00:27:00.289 the basal ganglia. There are five subcortical 00:27:00.289 --> 00:27:04.829 nuclei all working together to orchestrate movements. 00:27:05.829 --> 00:27:09.289 The basal ganglia is our goal, no goal areas. 00:27:10.089 --> 00:27:14.359 And this is where motivation and movements converge. 00:27:14.960 --> 00:27:18.700 But remember, the definition of motivation here 00:27:18.700 --> 00:27:22.900 is not defined by us and our ability to think 00:27:22.900 --> 00:27:26.740 and create. With our human cortex, motivation 00:27:26.740 --> 00:27:30.619 here is defined by the specific living organism. 00:27:31.240 --> 00:27:34.460 The nervous system just wants to respond. So 00:27:34.460 --> 00:27:37.339 that is the definition that you need to consider 00:27:37.339 --> 00:27:41.130 for motivation. The nervous system is it's going 00:27:41.130 --> 00:27:46.269 to respond based off of what it knows. This is 00:27:46.269 --> 00:27:51.809 a very different definition of motivation. So 00:27:51.809 --> 00:27:55.450 remember the five subcortical areas. There are 00:27:55.450 --> 00:27:58.809 inputs. So the cadet nucleus and the putamen. 00:27:59.470 --> 00:28:03.849 And then we have the globus pallidus internal 00:28:03.849 --> 00:28:09.490 and globus pallidus external. These form a triangle. 00:28:09.559 --> 00:28:14.619 two separate nuclei forming a triangle. And we 00:28:14.619 --> 00:28:19.940 also have the subthalamic nucleus, which is the 00:28:19.940 --> 00:28:22.660 personal assistant essentially to the thalamus. 00:28:23.420 --> 00:28:26.940 And of course the substantia nigra, the two nuclei 00:28:26.940 --> 00:28:32.299 here, the reticulata and the compacta. So these 00:28:32.299 --> 00:28:36.019 are all orchestrating movements based off of 00:28:36.019 --> 00:28:39.750 the environmental signals and the perception 00:28:39.750 --> 00:28:43.769 of the living organism's nervous system. We are 00:28:43.769 --> 00:28:47.630 orchestrating movements here. The direct pathway 00:28:47.630 --> 00:28:51.769 is trying to facilitate movements by reducing 00:28:51.769 --> 00:28:56.490 inhibitory outputs from these basal ganglia nuclei 00:28:56.490 --> 00:29:01.950 into the thalamus. This will send a signal up 00:29:01.950 --> 00:29:06.329 to the cortex for responses deemed necessary 00:29:06.329 --> 00:29:10.759 or efficient or practical, useful for the living 00:29:10.759 --> 00:29:17.660 organism. The start is neurons from the cortex 00:29:17.660 --> 00:29:22.160 of various areas of the cortex and some from 00:29:22.160 --> 00:29:24.880 the thalamus and some from the substantia nigra 00:29:24.880 --> 00:29:28.960 providing dopamine. These inputs are not exhaustive, 00:29:29.039 --> 00:29:33.319 but just kind of to explain the pathway. The 00:29:33.319 --> 00:29:36.099 direct pathway acts as more of the goal signal. 00:29:36.099 --> 00:29:40.000 So we're receiving excitatory dopamine from the 00:29:40.000 --> 00:29:44.339 substantia nigra. This is D1 -like dopamine, 00:29:44.940 --> 00:29:49.359 excitatory. The dorsal striatum then will communicate 00:29:49.359 --> 00:29:53.740 with the globus pallidus internal and the substantia 00:29:53.740 --> 00:29:58.400 nigra reticulata. It communicates to these two 00:29:58.400 --> 00:30:02.799 subdivisions by inhibiting them. It puts a break 00:30:02.799 --> 00:30:06.599 on them because the roles of the globus pallidus 00:30:06.599 --> 00:30:09.809 internal and the substantia nigra reticulata 00:30:09.809 --> 00:30:14.069 is normally to interact with the thalamus. So 00:30:14.069 --> 00:30:17.069 the dorsal striatum will shut these two nuclei 00:30:17.069 --> 00:30:21.309 off, and that frees up the thalamus. And the 00:30:21.309 --> 00:30:24.849 thalamus, being less inhibited, can then communicate 00:30:24.849 --> 00:30:29.369 back to the cortex, exciting the cortex and promoting 00:30:29.369 --> 00:30:35.970 movements. This pathway removes the break, removes 00:30:36.220 --> 00:30:41.539 the no -go side. The indirect pathway is a little 00:30:41.539 --> 00:30:46.640 bit more communication. It inhibits or kind of 00:30:46.640 --> 00:30:50.900 slows down movements, acting as a brake. So one 00:30:50.900 --> 00:30:56.220 is a go side and one is a no -go side. Similar 00:30:56.220 --> 00:31:00.460 to the direct pathway, signals come in to the 00:31:00.460 --> 00:31:04.400 input area, the conduct and containment from 00:31:04.400 --> 00:31:08.440 the cortex. and the thalamus and the midbrain. 00:31:08.579 --> 00:31:12.059 The dorsal striatum will then speak to the globus 00:31:12.059 --> 00:31:16.940 pallidus external, and it will inhibit the external 00:31:16.940 --> 00:31:22.279 area. By inhibiting the globus pallidus external, 00:31:23.079 --> 00:31:28.619 it will free up the subthalamic nucleus. It allows 00:31:28.619 --> 00:31:32.400 this area to be more active. Then the subthalamic 00:31:32.400 --> 00:31:36.569 nucleus will then speak to the Globus Pallidus 00:31:36.569 --> 00:31:40.809 internal, and the Substantia Nigra reticulata, 00:31:41.170 --> 00:31:44.369 essentially giving them free will, giving them 00:31:44.369 --> 00:31:49.630 a go -ahead signal to activate. Remember, the 00:31:49.630 --> 00:31:53.549 direct pathway inhibited these, so here we are 00:31:53.549 --> 00:31:58.269 exciting these two areas. The Globus Pallidus 00:31:58.269 --> 00:32:02.009 internal and the Substantia Nigra reticulata 00:32:02.009 --> 00:32:06.349 then speaks to the thalamus. The main goal. And 00:32:06.349 --> 00:32:09.190 these two nuclei to the thalamus says, stop. 00:32:10.049 --> 00:32:14.670 This is a no -go. And because the thalamus is 00:32:14.670 --> 00:32:20.049 inhibited or stopped, it can suppress or even 00:32:20.049 --> 00:32:23.089 slow down movements. It controls the movements. 00:32:25.089 --> 00:32:30.569 The indirect pathway is the no -go. And it uses 00:32:30.569 --> 00:32:34.849 the D2 -like dopamine. the inhibitory dopamine. 00:32:37.029 --> 00:32:39.150 What the basal ganglia is trying to accomplish 00:32:39.150 --> 00:32:43.650 here is fine -tuning of motor control. Remember 00:32:43.650 --> 00:32:46.390 the goal of the central nervous system. It's 00:32:46.390 --> 00:32:52.789 designed to move the living organism. What these 00:32:52.789 --> 00:32:56.750 two pathways are doing is fine -tuning of that 00:32:56.750 --> 00:33:01.490 motor control, this action selection. And remember 00:33:01.490 --> 00:33:05.970 the dorsal striatum is an area where goal -directed 00:33:05.970 --> 00:33:11.309 movements and behaviors are located and also 00:33:11.309 --> 00:33:16.809 habit formation. Our habits reside here. There's 00:33:16.809 --> 00:33:20.930 a lot of communication from sensory motor regions 00:33:20.930 --> 00:33:25.150 and the dorsal lateral side of the striatum, 00:33:25.390 --> 00:33:31.150 the DLS. Whereas the goal -directed resides more 00:33:31.150 --> 00:33:35.730 in the dorsal medial striatum, which is more 00:33:35.730 --> 00:33:40.450 cadet. So cadet is more go direction, and the 00:33:40.450 --> 00:33:44.150 pertainment is more habit formation. It's where 00:33:44.150 --> 00:33:47.490 habits live. And that's the goal of the central 00:33:47.490 --> 00:33:51.430 nervous system, though. We want to build learning 00:33:51.430 --> 00:33:58.009 and then send those down into habits. And these 00:33:58.009 --> 00:34:01.970 areas of the basal ganglia and this direct pathway 00:34:01.970 --> 00:34:06.670 and indirect pathway, this is how we can grasp 00:34:06.670 --> 00:34:10.670 our motor signals being processed and leading 00:34:10.670 --> 00:34:14.949 to how we coordinate downstream behaviors, downstream 00:34:14.949 --> 00:34:21.110 movements. Now Parkinson's here is a loss of 00:34:21.110 --> 00:34:24.730 timing and loss of energy. Now with everything 00:34:24.730 --> 00:34:29.019 with the substantia nigra, compacta and reticulata, 00:34:29.639 --> 00:34:33.000 you can start to understand why. The substantia 00:34:33.000 --> 00:34:36.559 nigra here, losing energy, losing its ability, 00:34:36.719 --> 00:34:40.360 its efficiency, it cannot conduct this pathway 00:34:40.360 --> 00:34:45.099 correctly. It loses its ability to coordinate 00:34:45.099 --> 00:34:49.699 these two direct pathway and indirect pathway. 00:34:50.659 --> 00:34:54.539 And if you think about it, with all the with 00:34:54.539 --> 00:34:57.519 the motor movements associated with Parkinson's 00:34:57.519 --> 00:35:02.320 and autism. This is pretty common and easy to 00:35:02.320 --> 00:35:07.099 understand here. The substantia nigra is lacking 00:35:07.099 --> 00:35:11.019 here and all of these downstream processes are 00:35:11.019 --> 00:35:16.400 off. So with autism, we get these stereotyped 00:35:16.400 --> 00:35:21.719 motor movements and stemming and repetitive restricted 00:35:21.719 --> 00:35:26.360 behaviors and so forth. In both Parkinson's and 00:35:26.360 --> 00:35:30.280 autism, it's easy to see. We love it when we 00:35:30.280 --> 00:35:34.960 can see things and observe and evaluate things. 00:35:35.139 --> 00:35:37.840 It's easy to see the motor movements here, the 00:35:37.840 --> 00:35:42.380 abnormal motor movements. In autism, it's well 00:35:42.380 --> 00:35:45.940 established that there's an increase of this 00:35:45.940 --> 00:35:50.980 D2 -like dopamine facilitated through the dorsal 00:35:50.980 --> 00:35:55.400 striata and it's implicated in the indirect pathway, 00:35:56.420 --> 00:36:01.400 we cannot inhibit motor movements. And over time, 00:36:01.960 --> 00:36:04.559 remember the discussions on neuroplasticity. 00:36:04.880 --> 00:36:08.599 These motor movements can actually become calming. 00:36:09.840 --> 00:36:13.340 We learn how to do these for calming. And they 00:36:13.340 --> 00:36:16.980 also remember the habit formation. We do these 00:36:16.980 --> 00:36:21.559 out of habit now. The more we do things, the 00:36:21.559 --> 00:36:24.719 easier it is to form the habit, which is the 00:36:24.719 --> 00:36:27.159 goal of the central nervous system. Because it 00:36:27.159 --> 00:36:30.039 doesn't want to work, it just wants to respond. 00:36:31.119 --> 00:36:33.820 And considering that the substantia nigra is 00:36:33.820 --> 00:36:38.300 not optimized, the transduction is not capable. 00:36:39.280 --> 00:36:43.719 Its loss of energy is very implicated here. This 00:36:43.719 --> 00:36:48.699 is what it's all about. If you look at go versus 00:36:48.699 --> 00:36:51.429 no -go and put them on a seesaw, The fulcrum 00:36:51.429 --> 00:36:54.409 there, the thing that is balancing on, is the 00:36:54.409 --> 00:36:57.110 substantia nigra and the dopamine coming out 00:36:57.110 --> 00:37:01.510 of the substantia nigra and into these other 00:37:01.510 --> 00:37:07.530 nuclei, facilitating these movements. If you 00:37:07.530 --> 00:37:09.670 are listening to the episode or listening to 00:37:09.670 --> 00:37:12.809 the podcast, please feel free to leave a review 00:37:12.809 --> 00:37:17.530 or rating. In podcasting, reviews, ratings, and 00:37:17.530 --> 00:37:20.349 downloads are huge. and I very much appreciate 00:37:20.349 --> 00:37:28.190 your feedback. You can contact me on X at rps47586 00:37:28.190 --> 00:37:31.889 and we can discuss anything about autism. I very 00:37:31.889 --> 00:37:34.570 much appreciate your comments and interaction. 00:37:35.789 --> 00:37:38.090 You can check out the hop link so you can have 00:37:38.090 --> 00:37:41.110 links to all of the shows across various podcasts. 00:37:42.489 --> 00:37:45.329 You can contact me on YouTube. Check out the 00:37:45.329 --> 00:37:49.400 YouTube channel and TikTok. I guess I'll try 00:37:49.400 --> 00:37:52.820 out TikTok. I'll see how that goes. I don't love 00:37:52.820 --> 00:37:58.840 it. But anyways, thank you for listening to From 00:37:58.840 --> 00:38:00.840 the Spectrum Podcast.