A 32-year-old man presents with progressive muscle weakness, cognitive impairment, and involuntary movements of upper limbs and facial muscles. A blood fi lm reveals spiked red blood cells. He is troubled by compulsive behaviour pertaining to order and symmetry.
Which of the following conditions is most likely?
A. The presence of spiked red blood cells (RBCs) together with ataxia, progressive weakness, and cognitive impairment is suggestive of neuroacanthocytosis. Patients with neuroacanthocytosis may also show personality changes characterized by impulsivity, distractibility, and compulsivity. Neuropathological findings include severe atrophy of the caudate and putamen with loss of neurones and an associated astrocytic reaction. Less severe changes are seen in the pallidum, thalamus, substantia nigra, and anterior horn cells of spinal cord. Acanthocytes are spiked RBCs seen in peripheral blood smears. Acanthocytosis is also seen in patients with abetalipoproteinaemia or hypobetalipoproteinaemia, where serum vitamin E and lipoprotein levels are abnormal.
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The recreational drug LSD exerts its hallucinogenic effect as a partial agonist at which of the following receptors?
D. The exact mechanisms of action of LSD and other hallucinogens are not completely understood as yet, but there is substantial evidence pointing towards serotonergic systems in the brain. Receptor-binding studies have shown that radiolabelled LSD binds to 5-HT2A and 5-HT1C receptors. Hallucinogens have agonist actions at the 5-HT2A receptor. The psychoactive and behavioural effects of hallucinogens are blocked by 5-HT2A antagonists. Tolerance/tachyphylaxis of hallucinogenic effect is related to down-regulation of 5-HT2A receptors. There may be a role for 5-HT2C receptors too in mediating the actions of hallucinogens. LSD is only a partial agonist at 5-HT2A, in contrast to the full agonist actions of other hallucinogens. The 5-HT2A receptor potentiates glutamatergic and dopaminergic neurotransmission when activated, while activating the inhibitory GABA interneurone system.
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Which of the following neurotransmitters is implicated in the neurobiology of addiction and behaviours associated with craving seen in recreational drug users?
B. The acute administration of all addictive drugs (except benzodiazepines) stimulates dopamine transmission in the projection from the ventral mesencephalon to the nucleus accumbens. This projection is generally referred to as the mesolimbic dopamine system. The site of action by which different street drugs activate dopamine can be classified into three distinct types:
Which of the following can be classified as a neurotrophin?
A. Neurotrophins comprise a family of proteins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins (NT)-3, -4/5, and -6. Proneurotrophins are enzymatically processed to create mature neurotrophins. Neurotrophins bind to specific tyrosine kinase receptors. Neurotrophins promote neuronal growth, differentiation, and survival, and modulate synaptic plasticity. These growth-related effects result from the interaction of neurotrophins with mitogen-activated protein kinase (MAPK) signaling pathway and the phosphatidylinositol-3 kinase pathway. In addition, the neurotrophins can inhibit cell death cascades. Reduced expression of neurotrophins such as BDNF has been proposed to underlie deficits in hippocampal neurogenesis seen in animal models of depression. Chronic antidepressant treatments are shown to upregulate neurotrophin expression, mediating relief from depression. Neurotrophin-mediated proliferation of hippocampal cells may be one of the fi nal common pathways of antidepressant effects.
Synthesis of adrenalin from noradrenalin requires which of the following enzymes in a neurone?
D. L-tyrosine is an amino acid derived from food proteins. It is also derived from the catabolism of phenylalanine in the liver by phenylalanine hydroxylase. L-tyrosine forms the precursor for the catecholamine neurotransmitters. Dopamine is the major initial product derived from L-tyrosine. Dopamine hydroxylase further converts dopamine into norepinephrine. In cells that contain phenylethanolamine N-methyltransferase (PNMT), norepinephrine undergoes further processing via methylation to produce epinephrine. Epinephrine is formed in trivial amounts in the CNS but is a major product in the adrenal medulla. Any drug that enhances the action of tyrosine hydroxylase and dopamine hydroxylase is likely to enhance noradrenergic transmission. Catecholamines are metabolized by two enzymes: monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT).
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