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Histology of Central Nervous System 1/5/10 cell types & structure

Cell types of the nervous system = neurons, support cells, and CT/vascular (only CT in CNS is directly connected w/vasculature).

axonal transport
:: Function = to transport proteins, organelles, lipids :: Types: transport goes in both directions: + anterograde = direction of cell body to synaptic terminal. Fxns to bring vesicles and proteins to the synaptic terminal for release. + retrograde = direction of synaptic terminal to cell body. Fxns to bring growth factors released by targets back to the perikaryon (b/c target cells send signals back to neurons to continue fxning) :: Speeds: + Slow = diffusion + Medium = proteins directly attach to microtubules and use them like a conveyer belt + Fast = >400mm/day. vesicles w/molecular “motors” attach to microtubules and use them as rails * Two types of molecular motors = kinesin and dynein families. Recognize the neg and pos sides of the microtubules. Kinesin = anterograde direction (transports vesicular contents, NT synthesizing enzymes (note NT’s are actually made in the synaptic terminal, so don’t need transporting themselves)). Dynein = retrograde direction (transports neurotrophic factors). Possible that lack of dynein may be associated w/neurodegenerative disorders. :: Clinical: + drugs are used to disrupt axonal transport. Drugs that disrupt microtubules such as vinblastin/vincristine etc block fast and medium axonal transport. If use these drugs for too long, get side effects of sensory neuropathies, etc. + disruption of axonal transport may be a commonality in many neurodegenerative diseases. Eg, in the “tauopathies” get accumulations of axonal tau, a tubulin-binding protein in neurons; this happens in Alzheimer’s, where the tau is hyperphosphorylated and may be interfering w/the retrograde axonal transport so the neurons can’t sense the trophic factors that are being sent back to them. :: Neuropil: is more a structural term than transport per se, but not sure where else to put it. Is essentially gray matter, and is made up of cell bodies, dendrites, and incoming axons w/their synaptic terminals. The axons can synapse virtually anywhere – on cell bodies (axosomatic synapse, which is a powerful signaling method), on dendrites (axodendritic synapse), and on other axons (axoaxonic synapse).

Neurons
:: morphologies + multipolar: in both CNS & PNS. Nearly ALL of neurons in CNS are of this type + Bipolar: are sensory, no dendrites, in both CNS (retina) & PNS (only in ganglia of CN VIII) + Pseudounipolar: are sensory, no dendrites, are in PNS only :: Cell body + has large, pale nucleus w/ prominent nucleolus. Large pale nucleus is indicative of ↑mRNA transciptional activity, prominent nucleolus indicates ↑rRNA transcriptional activity + large range sizes in order to support range axonal sizes (10-1000 microns) + Lots of RER – indicates lots of protein translation. Note see Nissl bodies = clumps of RER (when using acidophilic stain) + Lots of mitochondria – high metabolic rates + Lots of Golgi – high secretory fxn + note the cell body has no storage vesicles for glycogen etc. – neurons have no local energy capacity/reserves at all :: Dendrites + have extensive arborization (major diff from PNS, which has much less complex/fewer dendrites). Eg purkinje neurons of cerebellum, have primary, secondary etc dendrites, all the way out to what’s called a dendritic spine, the terminal branch. + function is to ↑receptive surface area of neuronal cell bodies, segregate different synaptic inputs (diff strengths, neurotransmitters, etc), and provide directionality of synaptic input + shape of dendritic arborization indicates function/what type of info it carries :: Axon + divided into 3 segments 1. Initial segment (axon hillock) = region w/lowest threshold for excitation – generates AP (no AP’s in dendrites or cell body). Looks pale/void on histo. 2. Axon proper = filled w/microtubules (fxn in transport) and intermediate filaments (neurofilament protein, maintains structural integrity). The plasma membrane (axolemma) is electrically excitable and conveys the AP to the synaptic terminal 3. Synaptic terminal = region where synaptic transmission occurs Support Cells = neuroglia = “nerve glue” Quick recap of PNS: support cells of PNS are the Schwann cells, which myelinate axons, buffer ions in the extracellular space, and phagocytize axons post-injury. Also have Satellite cells, which are associated w/cell bodies and dendrites rather than axons. For CNS, support cells broadly categorized into Macroglial cells, Microglial cells, and Ependymal cells. :: Macroglial cells + Astrocytes * Structure = protoplasmic (“naïve”, healthy astrocyte) or fibrous (at one point was phagocytosing). Glial Fibrillary Acidic Protein (GFAP) = type of interfilament protein uniquely expressed in astrocytes, may allow astrocytes to assume particular morphologies (note, pathologists looks for this when dx astrocyte tumors etc). When activated, astrocytes express all of the neurotransmitter receptors! * Have multiple fxns: 1. Maintain ionic environment (remove glutamate, K, etc) 2. Become phagocytic in response to injury (then turn into fibrous astrocytes) 3. Signal capillary endo cells to form tight junctions (ie BBB) 4. Signal arteriolar sm muscle cells to control local cerebral bl flow 5. All astrocytes in the brain are connected via an electrical syncitium. Fxn unknown. + Oligodendrocytes * Fxn is first/foremost to form myelin. Virtually all axons in CNS are myelinated (in peripheral fewer axons are myelinated). Also help maintain ionic env around axons (at nodes of Ranvier) so AP’s can propagate. * Myelin formation: a single Schwann cell is associated w/a single axon in the PNS, and can only myelinate a single “internodal segment”. However in the CNS a single oligodendrocyte can myelinate multiple internodal segments on multiple axons (note internodal segments in CNS are much shorter than in PNS) :: Microglial cells = brain macrophages + are monocytes that have left blood and now reside in the brain, move around monitoring for damage. + are activated by CNS injury to become phagocytic :: Ependymal cells = “spent” neural stem cells associated w/the ventricular area. + during development, stem cells give rise to marginal/intermediate zones that become white matter/neurons. The area that doesn’t grow becomes the ependymal cells, a single cell layer thick of ciliated cuboidal epithelial cells lining ventricular spaces of the CNS. However, in the area that forms as the choroid plexus, these cells become “modified” and form the epithelium of the choroid plexus: they produce CSF, and participate (tight junctions) in the bl-CSF barrier. (note, ependymal cells elsewhere in the brain do NOT form tight junctions, so CSF and brain parenchyma are in free communication.