They Discover The Role Of “Key” Of Astrocytes In The Formation Of Alzheimer ! http://newish.info/133360-they-discover-the-role-of-key-of-astrocytes-in-the-formation-of-alzheimer
No healing for you, spinal cord!
The nervous system can be divided into its various components in many ways. One way of dividing it up is into its different cell types. At its most basic form, this division splits the nervous system into neuronal cells and non-neuronal cells. Neuronal cells, as the name implies, encompass those most recognisable of cells - the neurons. The flagship of the cytoarchitecture of the nervous system. But of course, to those who have read any of my previous posts - there’s a world of other cells in the nervous system, not least the cells that make up the blood vessels and meninges, but in particular the glia. Glial cells outnumber neurons in the human nervous system. They outnumber neurons by a long way, with some estimates putting the ratio of glia to neurons at 10:1.
Perhaps the most ubiquitous of all the glia is the astrocyte. I’ve written about it before - they’re vital for nervous system function. They keep neurons alive, and also help the transmission of impulses (action potentials) in neurons by releasing various factors in the synapse. You understand that astrocytes are pretty darn important.
Astrocytes can also be scumbags. They’re one of the main reasons that the central nervous system (the brain and spinal cord) is so bad at repairing itself after injury. This is particularly the case in the spinal cord which contains a lot of nerve fibre tracts (aka white matter).
Diagram of a neuron. The axon (with it’s respective myelin sheath) is usually really really really long, and diagrams like this don’t do it any justice.
The nervous system is often divided into ‘White matter’ and ‘Grey matter’. This rather simplistic division can be rather effective. The grey matter is the tissue which predominately contains the synapses and cell bodies of neurons, and white matter is tissue which is occupied by the axons of the neurons. So basically, the white matter is the wiring of central nervous system. It is white because of the insulation around the axons, known as the myelin sheath (which can be likened to wires, as they propagate the electrical impulse, or the action potential). In the central nervous system, the myelin sheath is formed by a type of glial cell known as an oligodendrocyte. The insulation is made up of fat and protein giving white matter its white colour, and helps axons to conduct their nervous impulses at faster speeds.
Grey matter and White matter in a cross section of the spinal cord
Anywho, the spinal cord contains really long stretches of axons, which are descending from their cell bodies in the brain. Accidents which result in these axons being cut result in paralysis as the electrical impulses can no longer travel to their muscles. The information input into the respective muscle or glands has been cut so it can no longer be controlled by the brain - potentially causing paralysis.
Descending motor pathways. These nerve fibre tracts (in pink) are bundles of axons from neurons whose cell bodies start in the brain. The axons descend down the spinal cord to the level of the muscle they need to innervate, where they synapse with another neuron in the grey matter of the spinal cord (labelled as the ‘anterior nerve roots’ in the diagram). This subsequent neuron goes on to control its respective muscle. Cutting axons in the spine causes a break in this neural wiring, removing muscle control.
So a motorbike accident which results in paralysis most likely does so because the axons in the spinal cord get damaged. The region of the axon downstream from the lesion dies away, but the region of axon still attached to its cell body remains alive and actually tries to grow back.
Degeneration of the axon following a lesion (a cut/damage). The downstream region dies off, leaving the upstream region intact and ready to regrow.
The key word is tries. Try as lesioned axons might, their regrowth is physically impeded by spinal cord astrocytes. At lesion sites, astrocytes release a glycoprotein called chondroitin sulphate proteoglycan (CSPG) which plugs the gap. In laboratory animals, some axon regrowth can be acheived by removing this CSPG. This CSPG, although has some benefit, doesn’t seem to be a great loss to the nervous system when removed from a lesion site. The response is most likely a vestige from our evolutionary past which we don’t really need anymore. Aside from this, axon regrowth is impeded by the oligodendrocytes which express proteins on their surfaces which halt axon growth. Bearing this knowledge of inhibitory astrocytes in mind, however, much work has gone into working around this biological caveat and therapeutic strategies for spinal repair are on the horizon.
Diagram showing how astroglial CSPG halts axon regrowth. And how remvoal of CSPG theoretically should allow regrowth of axons, thus allowing nervous regeneration!
Spinal glia really become bastards when someone breaks their back.
List: Astrocyte Functions
Astrocytes are a special kind of stellate-shaped brain cells that are found throughout the central nervous system and that play a supportive role for neurons. For a long time, astrocytes were thought of as merely providing “assistance” for neuron function and survival. However, the discovery that astrocytes express voltage-gated channels and neurotransmitter receptors suggests the possibility of an active role for astrocytes in neuronal communication. Astrocytes primarily originate come from either radial glia cells or from cells in the sub ventricular zone and can be visualized with glial fibrillary acidic protein (GFAP). Below is an image of GFAP staining for astrocytes.
Other groups of glia:
- Oligodendrocytes: Provide myelin sheath in neurons present in the central nervous system (CNS). Each oligodendrocyte can myelinate multiple axons.
- Schwann Cells: Myelinate axons of neurons present in the peripheral nervous system (PNS). Schwan cells, however, only myelinate one axon.
- Microglia: Derived from bone marrow and function as antigen presenting cells. Microglia have phagocytic activity, which means they “eat up” (or clear) cellular debris and their roles are predominantly host defense.
- Regulation of brain extracellular pH via secretion of acid into the extracellular space (aka potassium buffering). Other regulatory functions of astrocytes include limiting the rise of both extracellular potassium (K+) and pH during neural activity. In addition, astrocytes can take up potassium in a variety of ways: Na+-K+ exchange, K+-Cl- cotransport and other K+ channels characterized by distinct properties.
- Regulating the uptake of glutamate near the synaptic cleft.
- Astrocytes can serve as signaling elements within an astrocyte network, between astrocytes and blood vessels, and/or between astrocytes and neurons. For example, astrocytes can signal to other neurons via Ca+2 oscillations (otherwise known as calcium waves). These calcium waves can come about in two ways: they are either triggered by neural activity (such as activation of astrocyte glutamate receptors) or spontaneoulsy via calcium release from internal stores and activation of IP3 receptors. Astrocytes may also serve as neurotransmitter transporters and receptors as well as aiding in neurotransmitter catabolism.
- Modulate synaptic and neural activity via “gliotransmission”. Known gliotransmitters (chemicals that can act on neighboring neurons, glial cells or vessels) include glutamate, cytokines, ATP, and D-serine. As illustrated below, astrocyte processes govern the amount of neurotransmitter spillage around synapse, thus controlling lateral spread of excitation.
- Modulation of brain vascular tone (i.e. vasodilation/vasoconstriction) and promotion of neurovascular coupling. Basically, astrocytes regulate cerebral blood flow. Moreover, vascular tone depends on the release of vascular agents into the perivascular space.
- Control of synapse formation, stabilization and function as well as neurogenesis. These roles have been predominantly explored in the context of brain pathology and psychiatric disorders like ALS, Alzheimer’s, brain tumors, traumatic brain injury and ischemia.
Chesler, Mitch. Properties of the brain, extracellular space and astrocyte function. Lecture given as part of the cellular neuroscience course. Fall 2009.
Just some casual energy storage
“My name is glycogen, short term energy source of short term energy sources:
Look on my α-1,6 glycosidic bonds, ye Mighty, and despair!”
Or something to that effect anyway. It sounded way better in my head.
Glycogen is a rather gnarly molecule which stores glucose. We absorb free, individual glucose molecules from the food we ingest, but we may not want to use all the glucose all at once - so we store some of it as glycogen. The glucose molecules can be stored as a polymer known as glycogen.
I felt compelled to share this wondrous molecule with the tumblrverse for the main reason that it has the most beautiful structure, almost fractal-like in its branching. Linear chains of glucose form the foundations of the glycogen molecules, where they are linked via α-1,4-glycosidic bonds, and the branches form from α-1,6 glycosidic bonds.
The carbons in glucose are specifically numbered, as shown above - which is where we get those names for the glycosidic bonds. Like in the diagram below!
The branched structure means we don’t need to store glucose in long linear chains which would just take up space. Might as well utilise more spatial dimensions than just one, after all. It’s a quick source of energy compared to fat as it takes a relatively simple chain of reactions from stimulus to glucose release to energy utilisation(glucagon, adrenaline etc, which indicate low blood glucose and energy expenditure respectively). Glycogen phosphorylase is an enzyme which releases a single glucose molecule from the chain, via attack of the glycosidic 1,4 bond with a phosphate. This cleaves off one glucose molecule with a phosphate attached to it, which is called glucose-1-phosphate.
Close up diagrams of the glucose chains which make up glycogen. Many of these add together to give the initial picture I started this post with.
The glucose-1-phosphate is then isomerised by an enzyme called phosphoglucomutase to glucose-6-phosphate (which means that the phosphate group is now attached to the 6th Carbon, as opposed to the 1st Carbon as it was when initially cleaved from glycogen), and this can enter straight into the glycolytic pathway for metabolising in order to release energy. Of course, many glycogen phosphorylase molecules will be recruited at once when required, and they’ll act at the various branches to systematically cleave glucose molecules off the glycogen to release vast quantities of glucose at once (the branching of glycogen provides a large surface area for glycogen phosphorylase enzymes to act, for simulataneous large scale release of glucose).
The glucose from glycogen is an immediate, first line source of energy in this way and is used up relatively rapidly, making time for the metabolism to prepare for the sustained, high energy release of fatty acid metabolism which is what the body inevitably switches too. Metabolising a fat takes longer than metabolising glucose molecules, but it releases looooads more energy and water.
But let’s not shift the attention from glycogen here. The majority of the brain’s energy comes from free-floating glucose in the blood, which is odd because the brain is such an energy expensive organ. There’s very little, if any, metabolically active fat in the brain, reason being that there just isn’t anywhere to store it in the compact cranial space. BUT there is some glycogen, stored in a type of non-neuronal brain cell called an astrocyte (part of a group of cells known as glia (or gleeeaaaa as my Scottish glia lecturer/dissertation supervisor says it, cause he’s awesome)). When neurons are highly active, possibly in response to some kind of experience the person is having, the free glucose in the blood is just not enough to sustain the neuronal function. Enter, astrocytes and their glycogen.
Electron micrograph of astrocytes in the brain. Red arrows are pointing to glycogen granules within the astrocytes.
Astrocytes can break down their glycogen to release glucose in times of high neuronal activity. The glucose is anaerobically metabolised into lactate - which is shuttled from the astrocyte into the neuron as a portable energy source to sustain the activity of, and power the changes in the neuron that occur in response to experience-related activity - in essence, driving neuronal plasticity - or even more in-essence, driving the processes that form memories.
To further this point, experiments in rats have shown that inhibiting brain glycogen metabolism impairs long term memory formation - BUT long term memory formation can be rescued by administering extra lactate to the rats brain! One hypothesis for sleep is that it gives the brain an opportunity to replenish depleted glycogen stores, which is one reason why sleep may be so important for memory formation and cognitive function.
Glia, glycogen and glucose - some winning players in brain function.