Man ought to know that from the brain, and the brain only arises our pleasures ,joy ,laughter and jests , as well as our sorrows ,pains ,griefs and tears!“
Hippocrates (460- 370 BC) Often referred to as Father of Medicine.
Brain is very much comparable to space where each expedition opens up yet another vista which is altogether anew! The brain is the organ which collects information from the internal and external environment, processes and stores it, and is retrieved in due course as reflected in our conscious as well as not so conscious behaviour and day to day activities. On the whole Brain makes us what we appear and what we are!
Brain as well as the entire nervous system is composed of neurons which communicate with each other and share information continuously round the clock! This has always been a matter of unbound curiosity for mankind from time immemorial.
It was the Nobel laureates, Dr Ramon Y. Cajal, Spanish neuroscientist of early twentieth century and a little later Dr Otto Loewi from Germany, who together pioneered the discovery of neurotransmitters. For the first time they propounded that the neurons are the signaling units of the nervous system which use certain chemicals known as neurotransmitters to talk to each other and deliver. This concept in itself has been a major milestone in the history of medicine and Neurosciences which gave Nervous tissue as a whole, a status of unique communicating organ system and Brain as its fountain head.
Neuron is the other name of nerve cell, a unit of nerve tissue such as brain or spinal cord. It consists of cell body in the middle containing nucleus, which prepares all important proteins that gives Neurons its integrity. It has two ends, the forward end is known as axon. The backward -receiving end is known as dendritic end which has many tails to which the axons of other neurons joins through synapses. . Each synapse , 20 to 50 nm ( one nano meter is billionth part of a meter ) long , a junction between two nerve cells or between nerve cell and other effector cells such as glands, where electrical signals liberate certain chemical , a neurotransmitter molecule specific to their functional objective . A Synapse has pre synaptic membrane followed by synaptic cleft, a potential space and post synaptic membrane on the other side. Electrical activity on the pre synaptic end is converted through calcium channels to release neurotransmitters which create a modified electrical current propagating to varieties of end organs such as skeletal muscles, skin, mucosa, secreting glands, immune system etc. These chemical molecules are of many types depending on the nature and function of the end organs, to name a few, Acetylcholine, Nor - adrenaline, Dopamine etc and many neuropeptides.
Professor Avid Carlsson of Goteborg university , Germany, for the first time established that Dopamine is the key transmitter molecule which controls movement . His research brought to the fore that lack of Dopamine, a neurotransmitter present in certain parts of the brain neurons, leads to paucity of movement, a kind of paralysis and therefore is the cause of “Parkinson’s Disease”. Professor Carlsson developed a bio - assay (measuring the concentration or potency in tissues) system to measure tissue level of Dopamine in different areas of brain such as basal ganglia (dense collection of neurons just below cerebral cortex) which has particularly very high level in normal state.
And to prove his point further L-Dopa , the direct precursor of “Dopamine “ when administered to the patients of Parkinson’s disease ,it improved the movement related disability quickly and almost regularly and since then it continues to be the mainstay of “Parkinson’s Diseases “ treatment . He used , extracts of plant of Indian habitat ( Raulphia Serpentina ) popularly known as ‘Sarpgandha ‘or Indian snake root , known as “Reserpine”when given to animals in laboratory , it depleted normally present Dopamine from brain tissues leading to pathological state of ‘Parkinsonism ‘. Again This plant extract induced Parkinsonism was easily reversed with the administration of ‘ L- Dopa’ , thus establishing the aetiology of Parkinson’s disease . This disease was first brought to the notice of modern medical science in 1817 by Dr James Parkinson by observing only six patients . The description given by Dr Parkinson in a paper titled “An essay on the Shaking Palsy “continues to be surprisingly accurate enough to be in current clinical practice as the main tool to diagnose Parkinson’s disease even two hundred years after!
Besides the discovery of neurotransmitter for the treatment for Parkinson’s disease, Professor Carlsson opened the floodgates for innovation in the field of Neuroscience and Psychiatry by introducing the major role of neurotransmitters. He propounded that it is the imbalance of different neurotransmitters which cause neuropsychiatric illnesses and it’s tactful manipulation can treat even intractable neurological and also mental illnesses such as , schizophrenia, bipolar disease , depressive disorder etc and opened entirely a new field of ‘psychopharmacology ‘. This de - stigmatised the treatment of neuro psychiatric diseases to some great extent and minimised the requirement of mental asylums!
Carlsson partnered with currently famous covishield vaccine maker AstraZeneca and developed SSRI (Selective Serotonin Receptor Inhibitors) drug, named as Zimeldin and later on Fluoxetine, a front line molecule to treat depression and anxiety. It broke all time sales record driven by its immense popularity!
Other Neurotransmitter such as Glutamate, is supposed to ‘prime’ the neurons to fire as and when appropriate. Schizophrenia and autism has been associated with reduced level of Glutamate production or its inability to be used by the neurons appropriately.
Likewise neurotransmitter Serotonin affects sleep, appetite and mood. Depressed people have lower levels of serotonin.
Dr Carlsson remained active till his last days and worked with his scientist daughter and produced a novel molecule code named as OSU 6162, a serotonin stabiliser to treat post stroke fatigue.
He was awarded the coveted Nobel prize in physiology or medicine in the year 2000 along with Dr Greengard of Rockfeller university, USA for elaborating the cellular mechanism of neurotransmitters and Dr Kandel of Columbia university for understanding the synapses in brain biology.
The Author is former Professor and Head of Medicine, RIMS, Ranchi.