Neuro (Subject) / Prüfung MolMed (Lesson)

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• Which receptor binds nerve growth factor (NGF)? TrkA-R
• The activation of which molecule(s) is/are associated with neuronal survival? NGF -> binds to TrkA -> AKT activation (master kinase for survival); target genes: FLIPs (FADD-like ICE inhibitory proteins -> procaspase decoys) and IAPs (XIAP, Survivin)The intrinsic apoptosis pathway involves activation of: CARD, Apaf-1, caspase-9
• Which is the difference between allodynia and hyperalgesia? Choose the correct definition: Allodynia= Pain resulting from normally painless stimulus; Hperalgesia= Excessive response and sense of pain to a normally painful stimulus.
• The terminals of nociceptive afferents release which one of the following transmitters? Glutamate, Substance P
• How is a nociceptor defined? A nociceptor is a sensory nerve cell that responds to damaging or potentially damaging stimuli => Free nerve endings in the skin.
• Which substance can activate TRPV1 channel, depolarize DRG neurons in a dose-dependent manner and give a burning sensation? Capsaicin
• Which type of subpopulation of DRG neurons are involved in nociception? peptidergic and non-peptidergic DRG neurons
• In mammals, a polarity signal (secreted protein) is released from the mesoderm which is necessary and sufficient to induce dorso-ventral polarity in the neural tube; the responsible gene is called ...? Sonic hedgehog
• The overall maturational pattern of histogenesis in the mammalian cerebral cortex as determined by autoradiography (rat) is ...? inside-out pattern of neurogenesis
• In vertebrates the conserved mechanism of midline crossing depends on Robo in the following pattern ...? precrossing: Robo3A high, Robo3B low, Robo1 low --> Attraction to floorplate postcrossing: Robo1 high (Slit induced), Robo3A low, Robo3B high --> Repulsion from floorplate
• Expermients that manipulate the afferent target of developing neurons such as removing muscle or transplanting an extra limb bud have shown that ... ? number of (motor) neurons depends on structures they serve/adapt to need -> eg if additional limb bud is transplanted -> reduced cell death of motor neurons and DRG cells compared to normal situation
• At the neuromuscular junction, a signal that is secreted from nerve terminals, induces receptor clustering; this proteoglycan is called ...? Agrin
• Which mammalian species show complex social lives and intelligent behavior? Compared to other mammals, how is their brain/body ratio? Brain/body weight ratio = Encephalization factor:--> humans have a bigger brain than expected for their body weight. --> Non-linear increase of brains = relative increase in brain size (humans exceed all other animals in terms of relative brain size !!) -->Human encephalization is driven by extensive use of hands and by the development of language (symbols and speech) Among primates humans show complex social lives and intelligent behavior. Compared to chimpanzees, the human neocortex:medulla ratio is two times larger. The human lateral prefrontal cortex is disproportionately large à increases the ability of humans to suppress reflexive responses to stimuli --> helps to evolve symbolic language (50.000-100.000 years ago) which causes behavioral changes independent of brain size
• How do you define ‚phylogenic reduction‘ in comparative neuroanatomy? Phylogenic reduction describes the phenome, that some animals have developed smaller brains than expected. E.g. salamander and lung fish
• What is the advantage of having a disproportionately large lateral prefrontal cortex? -->increases the ability of humans to suppress reflexive responses to stimuli --> helps to evolve symbolic language (50.000-100.000 years ago) which causes behavioral changes independent of brain size
• Which factors may be involved in mosaic versus concerted brain evolution? -->Mosaic and concerted evolution are terms that exist at opposite ends of a spectrum of evolutionary theories that explain variation in brain size. Mosaic evolution describes the adaptation of an organismal part as independent of similar adaptation in reasonably related parts, whereas concerted evolution correlates the adaption of an individual portion with the whole. The concerted hypothesis: Finlay and Darlington --> A factor that could create the magnitudes of variation in brain size is the duration and timing of cell division. The longer a time for progenitor cells to divide, the more cells would ultimately become neurons, and the larger the structure that forms in neurogenesis. mosaic genetisch und concerted timing/duration einflüsse zur brain evolution beitragen
• What does ‚Deacon‘s rule’ state? The greater invasion of spinal cord with increasing neocortical size fits an approxi mate relationship that has been called “ Deacon ’ s rule, ” which can be summarized as “ large equals well-connected. ”
• Which part of the brain shows the steepest slope in allometric development when compared to total brain volume? -->The Neocortex
• Which vertebrates do not exhibit a corpus callosum? The corpus callosum is only found in placental mammals while it is absent in marsupials (opossums, kangaroos) and monotremes (duckbill).
• Is neocortical folding a ‚shared derived‘ character in development? NO, it has developed independent among different species = ANALOGY -->Neocortical folding correlates with absolute brain size but not with phylogenetic orders -->Folding starts at a brain weight of 5-10g -->Hugh brains (e.g in dolphins) might be involved in thermogenesis
• Give approximate numbers for neuronal densities (numbers per volume) in the neocortex of mice, elephants and humans? Human`s neocortex: 16*10^9 neurons (84*10^9 neurons in the whole brain) Mice: Cortex=> 4*10^6 (total 71*10^6) Elephants: Cortex=> 5,6*10^9 (total 251*10^9) --> no/mm^3mice: 142 500elephants: 6 900humans: 10 500
• By what mechanisms are new structures developed in phylogenetic brain development? -->Larger brains are created by ‚stretching‘ brain development (keeping progenitors longer in the cell cycle), but regions maturing late are disproportionately large (‚late equals large‘, e.g. the neocortex) -->Human brain volume is maximal at age 8-9 (decreases slowly thereafter), but myelination and axon diameter increase to age > 30 -->Phylogenetically enlarged brain regions reveal more subdivisions (e.g. nuclei, cortical areas) and tend to become laminar (forming sheets) which minimizes connection lengths (conserves space and energy, e.g. the neocortex) -->Connection density decreases as neuron numbers increase - brains become modular -->The brain becomes energy-intensive: The human brain draws 15 watts of energy corresponding to appr. 16% of the entire body‘s energy consumption
• Which region/domain of voltage-gated ion channels defines the selectivity filter? S5/6
• Which modes of gating applies to voltage-gated ion channels? helical screw, transporter mode, paddle
• Which stimulus/stimuli can activate TRPV1 channels? Heat, Chilli (Capsaicin),pH
• How do Na+ ions permeate through voltage-gated Na+ channels? selectivity filter (basis of size, charge, energy of hydration of the ion)
• Which subcortical areas participate in the motor control? Basal ganglia, Cerebellum, Brainstem, Thalamus
• Which are the major projection neurons of the cerebellar cortex? Purkinje cell axon [inhibitory (GABA)] (the only output of the cerebellar cortex)
• Which pathways represent descending pathways of the motor cortex? Corticobulbar tract  corticospinal tract (pyramidal tract) Corticorubar and Corticoreticular tracts (extrapyramidal tract)
• Which functions are controlled by the cerebellum? planning of a movement  control of posture and equilibrium  control of smooth limb movements
• What is the characteristic for the direct pathway of the basal ganglia? Direct Pathway is overall Excitatory [Indirect Pathway is overall Inhibitory]
• What is characteristic for Huntington’s disease? most common hereditary neurodegenerative disease - prevalence 5-10 per 100.000 - progressive hyperkinetic movement disorder - progressive disturbance in drives, perception, thoughts and emotions - autosomal dominant disease (trinucleotide repeat disease, polyQ disease) Main Symptoms: motor – hyperkinesia, uncontrolled movements psychiatric – changes in the personality, dementia Pathology: progressive irreversible and selective neuronal loss dominating in the striatum degeneration of GABAergic projection neurons of the indirect pathway (D2 receptors) [degeneration of the direct pathway is also possible especially in juvenile forms] loss of GABAergic medium spiny neurons in striatumreduced inhibition of neurons of the external pallidumlater degeneration of other regions especially cortex intranuclear inclusion bodies (polyglutamine aggregates and proteins of the proteasome)
• What are the major clinical symptoms of Parkinson’s disease? Four cardinal symptoms: Bradykinesia, Akinesia, Rigidity, Tremor
• What is typical at pathological examination for the Parkinsonian brain? loss of DA neurons in substantia nigra (=striatal DA depletion)
• What are the specific features of multiple system atrophy? Clinical presentation: autonomic failure & motor disability  2 Forms: parkinsonism (MSA-P) and cerebellar ataxia (MSA-C) [but with time both come together] Neuropathology --> selective neurodegeneration: Striatonigral degeneration, Olivopontocerebellar atrophy, dysautonomia  Inclusion pathology of MSA: - GCI (glial cytoplasmic inclusion) [most common] - NCI (neural cytoplasmic inclusion) - NNI (neural nuclear inclusion)
• What is the function of autophagy and the proteasome system and what are there major features? Ubiquitin-proteasome system:  Responsible for a highly selective degradation of short-lived intracellular and plasma membrane proteins under basal metabolic conditions as well as misfolded or damaged proteins in the cytosol, nucleus and endoplasmic reticulum  Involves targeting of suscptible proteins by ubiquitin and only unfolded ubiquitinated proteins can pass through the narrow pore of the proteasome barrel  Autophagy: The process by which cells recycle their own non-essential, redundant or damaged organelles and macromolecular components  Adaptive response of the cell to sublethal stress such as nutrient deprivation, providing metabolites that can be used as fuel  Role in suppression of tumor growth, deletion of toxic misfolded proteins, elimination of microorganisms and antigen presentation  Autophagy forms: Macroautophagy, Microautophagy and Chaperone-mediated autophagy
• Which events are common for neurodegenerative disorders? progressive dysfunction and loss of neurons and synapses in selected vulnerable areas of the CNS  multifactorial - caused by genetic, environmental and endogenous aging factors  classified by genetic mechanism or protein deposition („protein misfolding diseases“) Common pathogenic mechanisms: abnormal protein dynamics  oxidative stress  impaired bioenergetics, mitochondrial dysfunction and DNA damage  dysruption of cellular/axonal transport  dysfunction of molecular chaperones  dysfunction of neurotrophins  neuroinflammatory/neroimmune processes
• What is the role of microglial activation in neurodegenerative disorders? MG have the greatest mitotic potential from all parenchymal cells of the CNS and are capable of self-renewal  Microglia are the immune cells/macrophages of the CNS  Microglial activation by: Cytokines, chemokines, ROS, NO  Microglia can be toxic if they produce NO, ROS, etc. but they can also be protective by clearing [TLR4: microglial cells (are major expressor of TLR4) can take up synuclein --> removement of TLR4 stops clearance of synuclein --> accumulation]
• Which cells are involved in the formation of the blood brain barrier? 1. (Richtig) Endothelial cells2. (Richtig) Microglia3. (Richtig) Astrocytes4.Neurons5.None of these
• Which peripheral immune cells can pass the blood brain barrier in neuroinflammation? 1. (Richtig) T cells2.Microglia3.Astrocytes4. (Richtig) Granulocytes5.None of these
• Due to the neurologic findings of muscle weakness, spasticity and sensory symptoms a 25-year-old woman was diagnosed with multiple sclerosis. Which of the following mechanisms contribute to her symptoms? 1.Schwann cells providing myelin sheaths on the axons in the central nervous system are degenerated2.Oligodendrocyte providing myelin sheaths on the axons in the peripheral nervous system are degenerated3. (Richtig) Oligodendrocyte providing myelin sheaths on the axons in the central nervous system are degenerated4. (Richtig?) Axonal degeneration of demyelinated axons5.None of these
• Which of the following statements is correct? neuromyelitis 1.(Richtig) Neuromyelitis optica is an astrocytopathy2.Neuromyelitis optica is an oligodendrocytopathy3. (Richtig) Neuromyelitis optica is an antibody mediated demyelinating disorder4. (Richtig) Neuromyelitis optica is an inflammatory demyelinating disorder5.None of these
• Which of the following statements is correct? anti NMDA 1. (Richtig)Anti-NMDA receptor antibodies modulate the function of the NMDA receptor2. Anti-NMDA receptor antibodies can activate complement and kill neurons by complement mediated cytotoxicity3.Anti-NMDA receptor encephalitis is an inflammatory demyelinating disease4. (Richtig)Anti-NMDA receptor antibodies lead to a transient loss of NMDA receptors on the cell surface5.None of these
• The part of the thalamus that relays visual information to the cortex is called? Lateral geniculate nucleus (LGN)
• Adjacent points in the retina that project to adjacent points in the higer order brain regions form a? retinotopic map
• NGFpromotes neurite outgrowth of the sensory neurons by activation of the receptor? trkA
• Which molecules play an important role for the segregation of neuroal crestcells from the neuraltube during development of the PNS? cadherins (cadherin-7)
• The activation of p75 receptor induces in sensory neurons ? apoptosis, growthcone collapse (ja nicht survival ankreuzen)
• The highly motal cytoskeleton of the tip of the neuronal growth cone consists of? actine, lamellipodia (actine network), filopodia (actin bundle), microtubuli
• TrkA is expressed by these subtypes of neurons from the dorsal root ganglia? small non myelinated nociceptors

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