Mini Museum 3 by

Docent: Andrew V. Schally

parmar57 — 2024-02-23 16:18:31 UTC

Andrzej Viktor "Andrew" Schally was born in Wilno, Poland, now known as Vilnius, Lithuania, in 1926. Living his early life during World War 2, Schally lived in a Jewish-Polish community in Romania. He moved to England in 1945, where he joined the National Institute of Medical Research¹. He then moved to Canada where he worked and studied at McGill University¹. At McGill, he studied endocrinology. He researched in a lab devoted to adrenal cortical steroids and ACTH. In 1955, he helped demonstrate the presence of corticotropin-releasing factors in the hypothalamic and neurohypophysial hormones, regulating pituitary function¹. In 1962, he became a citizen of the United States¹. Here, he led research in a VA laboratory devoted to the hypothalamus. After six months, he became the Chief of the Endocrine and Polypeptide Laboratories at the VA in New Orleans¹. In this lab, he eventually discovered the structure of certain key hormones such as thyrotropin-releasing hormones, luteinizing hormone-releasing hormones, and follicle-stimulation hormones². These discoveries led to the understanding that the hypothalamus was the controlling factor of the pituitary gland². As a result, he became a Nobel Laureate for Medicine or Physiology in 1977². This work opened the door to new research in contraception, diabetes, abnormal growth, and other mental disorders².

Sources:

https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

https://libguides.tulane.edu/famousalumni/AVSchally#:~:text=or%20Physiology%2C%201977-,Dr.,hormones%20and%20follicle%2Dstimulating%20hormones.

Discovery of Peptides

parmar57 — 2024-02-23 21:11:12 UTC

The Fischer peptide synthesis is what is presented here. It shows how to artificially synthesize peptides for experimentation. Emil Fischer discovered peptides at the beginning of the 20th century. Fischer wanted to understand protein synthesis. He contributed to the knowledge of proteins by separating and identifying individual amino acids¹. He discovered peptides such as glycogen by reacting different proteins together. To do so, Fischer produced phenylhydrazine, a base that helped reveal sugar molecules' structures which allowed him to produce several sugars artificially and map the structure of their molecules². Additionally, Fischer discovered the method the peptide synthesis by elongating a peptide through a reaction of amino acids and then removing a reversible protecting group². This discovery of peptides was the foundation of protein synthesis. It inspired further research on protein synthesis and peptide formation, leading to a better understanding of how the human body works and neurotransmission as well. Without Fischer's discovery, Schally wouldn't have been able to explore the role of peptides in the nervous system.

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De Usu Partium

parmar57 — 2024-02-23 21:58:07 UTC

The De Usu Partium is a collection of works written by Galen between 165 CE and 175 CE in Rome. In this work of anatomy and physiology, Galen describes different body parts and their function¹. He reveals basic medical concepts and anatomical details¹. Roman laws didn't allow people to dissect animals². He found these anatomical structures and learned physiology through his live dissections called vivisections on animals². These animals include pigs and dogs². In De Usu Partium, Galen describes the hypothalamic infundibulum and the pituitary gland as the draining route and receptacle for mucus passing from the brain ventricular structures to the nasopharynx³. Even though he was wrong, Galen's contributions to anatomy inspired generations of scientists to further research the human body. Moreover, his discovery of the hypothalamus and pituitary gland inspired heavy research on the brain.

https://watermark.silverchair.com/jama_207_12_036.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAz8wggM7BgkqhkiG9w0BBwagggMsMIIDKAIBADCCAyEGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMSlvlOfojbgwrsy3pAgEQgIIC8i7G_6SKviFrn-gBlxnEJaDWCnjxUYCEjbHpEMGoso7JIDLWBXtkJ5cuk3iTCSJ56mHecbCZSqERyFPCU_KHYNKh2UvHF7KdDBTVpZzBDd530iFjTaGaHLScDxAxwYsJ3T-zl-jsPKdIrt3-79SZlofKkWZv-hRx8rx2MzuVuutupfhvi3WzM8XogrsXVG74IrXBMBxHnTWJp87PLYoVavuy09ZzxD6gSOyg9iSyNsJvJQ3aD-4P4fNdJEmTQq07ANvcQxCs0aLXyNfZRZyB4xY7XdSmc1E2XgK0IelyeuBcVjgjRsPCq8iaFjcuLK_iIbhSprlFifvT_Px0VIFZcdcFmSeGtlqRycVvhhyNnvSeMIigKbepm0m9Sp30R0T6RVtxq1A4IN6kMfZecJUnXb7R7r0fwcJPcSKUIjR29Yn6cyKd3FdpKTvqWgqBoljCwpasGVPPqjbBC7Lb3qtrzb1yvJVFAPgI5RYUGGtUiscs9Vbm5mJuivgOgJqAxZ1I-P8C0XxVlY5_I3xDhjfASLt0tlmCR8siNOCATlw85HG-cv_Y5KLEnVpmd_dC4VjD367Wyj8y1P2L4-dka24irBerDwKvFo2Gf_oWQR627BBNtYa1xEgjMMk-66ktlaSCA39g0jH3JvKfj_u_47uDNRjMD5lXDBBvVXvMtWqcz1QmL0vCjv_FsgxRuhfavtkhqxuJ2OmpPslLQRZxHec62MmejqvjGMVBnjnNfSF9EH82CYxpX5aEuXg7wElanzJ9RKhn6gpYf11ITKJWz6Q2zQID0m7WTh4BORbgKp1eph_qQgdtP0_7uKDp9XC23CIYYV1VBfJJ5MQ7rNSyvsj2chxzJ4OJifMriyCKK7jO7pwRFqnioXNN3vY8Qi-CYM0nzCyKe0dziKGc88A86egHzxISTH1xMEi8nKgFMLhBEsTOBpZSgNCGM17sS8izEzasuNMussSGI3zxaeeUpXN0Hsi6A_qafZ0ViKPiXlr-DNW7ZKo

Amaker, T., Barber, C., Benson, A., Beyerl, Z., Bogdan, K., Crocker, L., Doppelheuer, E., Gonzalez, H., Heal, S., Strong, R., O’Dell, A., O’Haren, D., Pavlish, J., Prus, L., Reese, E., Sasnett, M., Shadinger, J., Smith, A., Todd, S., … Rothemich, K. (2020b, July 29). Galen’s Anatomical Anomalies & Discoveries. Science Technology and Society a Student Led Exploration. https://opentextbooks.clemson.edu/sciencetechnologyandsociety/chapter/ancient-anatomy-galen/

https://www.ncbi.nlm.nih.gov/books/NBK279126/#:~:text=Galen%20described%20the%20hypothalamic%20infundibulum,the%20pituitary%20gland%20the%20rete

The hypothalamus' true function

parmar57 — 2024-02-23 22:33:21 UTC

Wilhelm His Sr., a pioneer of neuroembryology, defined the modern interpretation of the hypothalamus. His' ideas supported the transversal nature and general comparable dorsoventral patterning of the alar plate¹. His was a Swiss anatomist who invented the microtome². The microtome is a specialized precision cutting instrument that accurately and repeatedly slices sections from a block of embedded tissue². Using these technologies, His could better study the organization and function of tissues and cells under a microscope¹. In doing so, he created this drawing, which models the forebrain subdivisions. The hypothalamus was the V.1 region¹. Without His' discovery, Schally wouldn't have been able to understand the role of the hypothalamus to this extent. His' discovery of the true nature of the hypothalamus contributed to Schally's research on peptide formation in the brain.

De Systeme Nerveux

parmar57 — 2024-02-23 22:53:56 UTC

Marie Jean Pierre Flourens (1794-1869) was a French physiologist who believed that the brain acted as a functional entity where specific parts of the brain controlled specific functions. He used ablation and stimulation methods on mammalian species to discover his findings. Flourens had several significant discoveries related to the nervous system that heavily advanced the field of neuroscience and psychology¹. For example, he believed that the medulla is responsible for many vital functions such as respiration¹. His use of ablation in experimentation led to a better understanding of localized functions in the brain. While his experimentation was crude and rudimentary, it was a byproduct of his time since he didn't have the accurate knowledge or proper equipment to conduct these experiments². Flourens' ablation studies were critical for advancing knowledge on brain localization and function². Moreover, Flourens disproved the pseudoscience practice of phrenology, preventing further neuroscientists from following the wrong path². Flourens' research greatly impacted the future of neuroscientists, leading to a new sector and thought of how the brain functions.

This work presented is Flourens' Du Systeme Nerveux. This works that explain the nervous systems and its several functions.

Sources:

1) Yildirim, F. B., & Sarikcioglu, L. (2007). Marie Jean Pierre Flourens (1794 1867): an extraordinary scientist of his time. Journal of neurology, neurosurgery, and psychiatry, 78(8), 852. https://doi.org/10.1136/jnnp.2007.118380

2) https://karger.com/ene/article/61/5/311/124627/Marie-Jean-Pierre-Flourens-1794-1867-and-Cortical

Electroshock Brain Therapy

parmar57 — 2024-02-23 23:05:04 UTC

Electroshock was introduced by Ugo Cerletti in 1930 as the first modern example a of therapeutic application of brain stimulation for severe psychosis¹. The electric current evoked an epileptic seizure that somewhat remodeled the neural connections, helping patients improve¹. This idea was inspired by the belief that the brain passed messages through only electrical signaling, not with chemical signaling. As a result, many brain stimulation technologies were originally based on electrical stimulation, not chemical stimulation. This viewpoint slowly changed over time as new discoveries were made.

This entry is presented to show the early stages of neurotransmission understanding². Without understanding the purpose of electric potentials in the brain, other understandings of brain signaling and neurotransmission would not have been possible².

1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157831/#:~:text=Electroshock%2C%20introduced%20by%20Ugo%20Cerletti,1940%3B%20Kalinowsky%2C%201986).

2) https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/action-potentials-and-synapses#:~:text=Synapses%20can%20be%20thought%20of,into%20or%20out%20of%20the

Corticosteroid treatment origins

parmar57 — 2024-02-23 23:14:03 UTC

In 1933, American chemists successfully isolated cortisol within extracts from the adrenal gland¹. In 1948, the first patient with rheumatoid arthritis was treated with cortisone and then other rheumatologic patients received the same treatment soon after². This started a new investigation into cortisol and corticosteroids². They understood that cortisone stimulates native cortisone production, ACTH. Many researchers started looking into this line, including Schalley when he went to McGill. Schalley's research on cortisone and ACTH inspired him to further his pursuit of endocrinology, leading him to eventually create a lab for the VA and Tulane which led to his Nobel Prize³.

https://cortisone-info.com/en/general-information/what-is-its-history/#:~:text=In%201933%2C%20a%20team%20of,issued%20from%20these%20animal's%20glands.

https://pubmed.ncbi.nlm.nih.gov/22018177/

https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

Ergot and Acetylchlorine

parmar57 — 2024-02-23 23:29:12 UTC

Ergot has always been referenced throughout history¹. Ergot mushrooms have often been known to give people hallucinations, paranoia, twitches, and many more reactions. In the Middle Ages, it was often mixed with flour unintentionally, causing many people to be afflicted by these symptoms¹. It has even been referenced in a tablet from 600 BC. Henry Hallett Dale (1875-1968), an American pharmacologist, discovered that ergot mushrooms had many pharmaceutical properties. With the help of chemists, he was able to extract many amines, such as one similar to adrenalin and acetylcholine². With the help of a chemist, Dale could describe the chemical structure and pharmacological action of drugs that mimicked nerve stimulation in the nervous system². He found that acetylcholine best mimicked stimulation of parasympathetic nerves². By 1936, he confirmed that neurotransmitters were secreted at all peripheral synapses and through leech experimentation, he found that acetylcholine was released at the neuromuscular junction². This led to the discovery that there were possibly chemical interactions in neurotransmission, something with Schalley further explored.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640538/

https://karger.com/ene/article/60/3/162/123616/Henry-Dale-and-the-Discovery-of-Chemical-Synaptic

Confirming Chemical Transmission

parmar57 — 2024-02-23 23:49:44 UTC

Otto Loewi, a Pharmacology professor in Austria, found evidence that supported the chemical mediation of nerve impulses. He stimulated the vagus and sympathetic fibers to the frog's heart and isolated the two substances that had different effects when applied to a second heart preparation¹. He called Acceleransstoff the substance that stimulated the sympathetic stimulation and Vagustoff the substance that stimulated vagal stimulation¹. Through his experimentation of frog hearts in 1921, Loewi concluded that chemical messengers had to play a part in neurotransmission². Specifically, he found out that acetylcholine was a chemical messenger that played a part in neurotransmission. Through his research, he discovered several components of chemicals and neurotransmission that are still taken into account today². Loewi provided the foundation and evidence for Dale's initial research. His research was instrumental to Schally's understanding of peptides and neurotransmission by setting the foundation that chemical substances affect neurotransmission.

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Thryotropin-Releasing Hormone

parmar57 — 2024-02-24 00:05:59 UTC

Schally's primary research was on the hypothalamus and pituitary gland. Starting in 1962, Schally researched Thryotropin-releasing hormone (TRH). It's a hormone produced by neurons in the hypothalamus that is widely distributed in the CNS and regarded as a modulator of neuronal activities in extrahypothalamic regions¹ including the cerebellum. It has an important role in regulating energy homeostasis through its regulation of thyroid hormone levels. Schally specifically was able to isolate TRH and determine the amino acids. His lab was able to determine the correct amino acid sequence and subsequently, the structure. As a result, he was able to synthesize TRH, helping greatly advance studies regarding it.

Luteinizing hormone-releasing hormone

parmar57 — 2024-02-24 00:12:34 UTC

Once he finished his efforts on TRH, Schally focused on Luteinizing hormone-releasing hormone (LH-RH) as he saw its potential in clinical applications. Schally first isolated LH-RH from several hypothalami and proved it as a polypeptide¹. He then completed the structure and confirmed it by synthesis. He found that LH-RH was a physiological hormone and he was able to create synthetic LH-RH readily available¹. Once readily available, he further moved his efforts. However, his research on LH-RH was incredibly important. Through LH-RH testing, we can better predict ovulation cycles and testosterone release to better understand how to support pregnancies². This, along with his research on TRH, helped him win the Nobel Prize in science.

Sources:

1) https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

2) https://www.ncbi.nlm.nih.gov/books/NBK539692/#:~:text=In%20males%2C%20LH%20stimulates%20testosterone,the%20corpus%20luteum%20%5B8%5D.

Contemporary Entry: Neuropeptide Therapy

parmar57 — 2024-02-24 03:12:25 UTC

Schally's Nobel Prize-winning research inspired many scientists to look into neuropeptides. So far, many researchers have found that neuropeptides modulate the activity of co-released neurotransmitters to increase or decrease the strength of synaptic signaling¹. Neuropeptides function similarly to peptide hormones and modulate nearly all bodily functions¹. Now, people have started to use neuropeptides for several functions. For example, neuropeptide theory has been heavily researched. Neuropeptides help increase various growth factors in the brain and enhance what the brain is naturally capable of doing². Neuropeptide therapy helps with energy, concentration, mood regulation, and much more. Current researchers are trying to see if peptide therapy can help address neurodegenerative diseases such as Alzheimer's and dementia. For example, amino acid modifications and enhancing delivery and pharmacokinetics have drastically improved treatments for neurodegenerative diseases¹. Schally leaves behind a lasting legacy in the neuroscience world as he sets the foundation a new sector of neuroscience and a new set of treatments and preventative measures for neurological diseases.

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