The majority of serotonin in the human body is found in:
C. The majority of distributed serotonin in human body is located in the intestines. Due to the wide distribution of serotonin receptors, side-effects of serotonergic drugs may be variable; for example 5-HT3 receptors in the area postrema or the hypothalamus are associated with nausea and vomiting. The receptors in the basal ganglia are associated with akathisia and agitation. Limbic receptors are associated with an anxiety response when serotonergic drugs are administered initially. The serotonin receptors in spinal cord may produce sexual dysfunction. The intestinal receptors constitute nearly 90% of the body’s serotonin receptors. Hence the common side-effects with most serotonergic drugs are gastrointestinal upset and diarrhoea.
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Which of the following is a feature of a second messenger?
E. The neurotransmitter that brings a signal to a neurone is considered to be the ‘fi rst messenger’. For the signal to get across to the postsynaptic neurone, it must be transformed into an intraneuronal message. This is enabled via formation of the ‘second-messenger’ molecules. Second messengers generally do not act outside the cell of origin. The most commonly encountered second messengers include cAMP and cGMP, the calcium ion (Ca2+), and the phosphoinositol metabolites such as inositol triphosphate (IP3) and diacylglycerol (DAG). Gases such as nitric oxide and carbon monoxide also act as intraneuronal second-messenger molecules. The second messengers are not hormones as they do not reach tissues via the blood stream. Unlike receptor proteins, they do not combine with the neurotransmitter molecules directly. They are present throughout the CNS.
A 55-year-old man presents to A&E dreading that he has had a stroke. He has a weakness on the right side of his face with drooling of saliva from the right corner of his mouth. On examination he is not able to close his right eye fully and cannot hold air against his right cheek. When attempting a wrinkle, the right eyebrow appears sluggish. He is not able to whistle properly. He has normal tone and power in all four limbs.
Which of the following clinical signs can be expected?
A. This patient’s presentation is suggestive of Bell’s palsy. It is the most common cause of facial paralysis, usually occurring on one side only. The lifetime prevalence is about 1 in 60 in the UK. It is most commonly seen between the ages of 15 and 45, in both men and women. Pregnancy and diabetes may increase the risk of Bell’s palsy substantially. Though the exact cause is not known, a viral etiology is suspected (herpesvirus). The symptoms usually develop overnight. Most patients present with difficulty closing the eye, drooling of saliva, and sagging of the eyebrow on one side. Less commonly, patients may have heightened sensitivity to loud noise on the affected side. Most patients (nearly 80%) recover completely within 3 weeks. Almost all patients recover within 6 months. Patients with Bell’s palsy exhibit Bell’s phenomenon. Bell’s phenomenon is a normal defense refl ex present in about 75% of the population. It results in elevation of the globes when shutting eyes closed or when the eyes are directly threatened by external agents. Such upward movement helps to protect the most important structures (cornea and lens) of one’s eyes. This elevation becomes noticeable when the orbicularis muscle becomes weak as in Bell’s palsy. Bilateral Bell’s phenomenon is found in myasthenia gravis, sarcoidosis, bilateral Bell’s palsies, congenital facial diplegia, some rare forms of muscular dystrophy, motor neurone disease, and Guillain–Barré syndrome.
Regarding the serotonin (5-HT) system in the brain, which of the follow statements is false?
C. Serotonergic cells are localized in the brainstem in a group of nuclei called the raphe nuclei. In contrast to the more circumscribed dopaminergic pathways, almost all parts of the brain receive serotonergic input. This probably explains the multiple effects of serotonin receptors on mood and behaviour. All serotonin receptors are G-protein linked, except 5-HT3 which is ligand gated. Serotonin does not cross the blood–brain barrier and thus the brain synthesizes its own serotonin. This is in turn determined by concentrations of free plasma tryptophan and transport across the blood–brain barrier. This forms the basis of the rapid tryptophan depletion test. Tryptophan hydroxylase hydroxylates tryptophan to 5-hydroxy tryptophan (5-HTP), which is further decarboxylated to serotonin (5-HT) by aromatic-L-amino acid decarboxylase (AADC) in the presence of vitamin B6 as coenzyme. The rate-limiting step in serotonin synthesis is considered to be the availability of 5-HTP. In parallel with dopamine and norepinephrine, following release into the synaptic cleft, 5-HT is either metabolized or actively transported back into the neurone by a high-affinity transporter, the serotonin reuptake transporter (SERT). SERT is encoded by a single gene on chromosome 17. The SERT gene has been recently postulated to play an important role in gene–environment interaction in disorders such as depression.
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Prion protein PrPC is seen in normal cells. Pathological changes in this protein can lead to neurodegenerative changes seen in Cruetzfeldt– Jakob disease.
Which of the following explanations in most likely for the pathological variation?
C. Prion protein (PrP) is a glycoprotein anchored to neuronal cell membranes. The normal function of prion protein is not known. Bovine spongiform encephalopathy (‘mad cow disease’) and Crutzfeldt–Jakob disease are associated with altered prion proteins. In prion diseases, the normal cellular form of PrP (called PrPC) undergoes transformation to an altered version (called scrapie-associated prion protein PrPSc). The latter accumulates in the brain to form insoluble aggregates, leading to neuronal dysfunction, but unlike other neurodegenerative diseases, prion diseases are transmissible. This is made possible because PrPSc imprints its pathological conformation onto other, normal PrPC molecules, thus ‘converting’ them to be abnormal. PrPC and PrPSc do not differ in their amino acid sequences.
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