Chromatolysis
Encyclopedia
Chromatolysis is the dissolution of the Nissl bodies
in the cell body of a neuron. It is an induced response of the cell usually triggered by axotomy
(severing or damaging of the axon), ischemia
, toxicity to the cell, cell exhaustion, virus infections, and hibernation in lower vertebrates. Neuronal recovery can occur after chromatolysis, but most often it is a precursor of apoptosis. The term "chromatolysis" was initially used in the 1940s to describe the observed form of cell death characterized by the gradual disintegration of nuclear components; a process which is now called apoptosis
. Chromatolysis is still used as a term to distinguish the particular apoptotic process in the neuronal cells, where Nissl substance disintegrates.
ian ovarian follicle
s. The cells showed variable stages of pyknotic chromatin. These stages included chromatin condensation, which Flemming described as “half-moon” shaped and appearing as “chromatin balls” (large, smooth, and round electron-dense chromatin masses). Other stages included cell fractionation into smaller bodies. Flemming named this degenerative process “chromatolysis” to describe the gradual disintegration of nuclear components. The process he described now fits with the relatively new term, apoptosis, to describe cell death.
Around the same time of Flemming’s research, chromatolysis was also studied in the lactating mammary gland
s and in breast cancer
cells. Based on the findings of these studies, some researchers argued for the existence of a necessary cellular process to counterbalance the proliferation of cells by mitosis. It was proposed that chromatolysis played a major role in this physiological process. Chromatolysis was also thought to be responsible for necessary cell elimination in various organs during development. Again, these expanded definitions of chromatolysis are consistent with what we now term apoptosis.
In 1952, research further supported the role of chromatolysis in changing the physiology of cells during cell death processes in embryo development. It was also observed that the integrity of mitochondria is maintained during chromatolysis.
By the 1970s, studies identified the conserved structural features of chromatolysis. The consistent features of chromatolysis included the condensation of the cytoplasm and chromatin, cell shrinkage, formation of “chromatin balls,” intact normal organelle
s, and fragmentation of cells observed by the budding of fragments enclosed in the cell membrane. These budding fragments were termed “apoptotic bodies,” thus coining the name “apoptosis” to describe this form of cell death. The authors of these studies, most likely unfamiliar with older publications on chromatolysis, were essentially describing a process identical to chromatolysis.
, nucleus, and cell body. The nucleus becomes elongated and organization of Nissl bodies is disrupted. The process of Nissl dissolution is less apparent toward periphery of the cell body of the neuron, where normal-looking Nissl bodies may be present. This loss of Nissl bodies propagating from the center of the cell body outward is known as central chromatolysis. In neurons receiving axonal transection, central chromatolysis is observed in the area between the nucleus and the axon hillock following.
The enlargement of nuclear components due to axotomy can be explained by the alteration of the cell’s cytoskeleton
. The cytoskeleton maintains the nuclear components of a cell and the size of the cell body in neurons. The increase in protein within the neuron leads to this change in the cytoskeleton. The increase in protein can be explained by the increase in cytoskeleton size. Changes in the cell body cytoskeleton seem to be responsible for enhanced nuclear eccentricity following axonal injury.
One hypothesis behind the incidence of chromatolysis following axotomy is that the shortening of the axon prevents the incorporation of the axon
al cytoskeleton that undergoes formation in the injured neuron. Nuclear eccentricity can be attributed to the presence of excess axonal cytoskeleton between the nucleus and axon hillock, which causes chromatolysis. A second hypothesis proposes that blockage of axonal cytoskeletal proteins causes chromatolysis.
Central chromatolysis is the loss of basophilic staining after axotomy. The loss of staining begins near the nucleus and spreads toward the axon hillock. The basophilic rim is formed as chromatolysis compresses the cytoplasmic skeleton.
for 3, 6, and 12 days and the A- and B-cell perikarya of their L5 dorsal root ganglion
were examined. There was no morphological change in the B-cell perikarya, the A-cell perikarya however exhibited chromatolysis in 11% and 23% of the population, for the 6 and 12 days groups respectively. Acrylamide intoxication resembles neural axotomy histologically and mechanically. In each case the neuron undergoes chromatolysis and atrophy
of the cell body and axon. Also both seem to be mechanically related to a disruption of the delivery of neurofilament to the axon due to a decreased transport of a trophic factor from the axon to the cell body.
(ALS). Patients with ALS appear to have significant alterations that occur within the chromatolyzed neuronal cells. These alterations include dense conglomerates of aggregated dark mitochondria and presynaptic vesicles, bundles of neurofilament
s, and a marked increase of presynaptic vesicles. Changes to the function of the motor neurons have also been observed. The most typical functional change in chromatolytic motor neurons is the significant reduction in size of the monosynaptic excitatory postsynaptic potentials (EPSPs). These monosynaptic EPSPs also seem to be prolonged in the chromatolyzed cells of ALS patients. This functional change to the anterior horn neurons could result in the elimination of certain excitatory synaptic inputs and thus give rise to the clinical motor function impairment that is characteristic of the ALS disease.
al, and myelin degradation, accompanied by non-supportive inflammation and changes in spongiform of various regions of grey matter. A significant loss of neurons due to hippocampal degeneration has also been observed. The degenerate chromatolysis neurons seldom showed intracytoplasmic labeling for PrP.
Nissl body
A Nissl body is a large granular body found in neurons. These granules are rough endoplasmic reticulum and are the site of protein synthesis...
in the cell body of a neuron. It is an induced response of the cell usually triggered by axotomy
Axotomy
An axotomy is the cutting or otherwise severing an axon. Derived from axo- and -tomy . This type of denervation is often used in experimental studies on neuronal physiology and neuronal death or survival as a method to better understand nervous system diseases.Axotomy may cause neuronal cell...
(severing or damaging of the axon), ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, toxicity to the cell, cell exhaustion, virus infections, and hibernation in lower vertebrates. Neuronal recovery can occur after chromatolysis, but most often it is a precursor of apoptosis. The term "chromatolysis" was initially used in the 1940s to describe the observed form of cell death characterized by the gradual disintegration of nuclear components; a process which is now called apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Chromatolysis is still used as a term to distinguish the particular apoptotic process in the neuronal cells, where Nissl substance disintegrates.
History
In 1885, researcher W. Flemming described dying cells in degenerating mammalMammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
s. The cells showed variable stages of pyknotic chromatin. These stages included chromatin condensation, which Flemming described as “half-moon” shaped and appearing as “chromatin balls” (large, smooth, and round electron-dense chromatin masses). Other stages included cell fractionation into smaller bodies. Flemming named this degenerative process “chromatolysis” to describe the gradual disintegration of nuclear components. The process he described now fits with the relatively new term, apoptosis, to describe cell death.
Around the same time of Flemming’s research, chromatolysis was also studied in the lactating mammary gland
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
s and in breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
cells. Based on the findings of these studies, some researchers argued for the existence of a necessary cellular process to counterbalance the proliferation of cells by mitosis. It was proposed that chromatolysis played a major role in this physiological process. Chromatolysis was also thought to be responsible for necessary cell elimination in various organs during development. Again, these expanded definitions of chromatolysis are consistent with what we now term apoptosis.
In 1952, research further supported the role of chromatolysis in changing the physiology of cells during cell death processes in embryo development. It was also observed that the integrity of mitochondria is maintained during chromatolysis.
By the 1970s, studies identified the conserved structural features of chromatolysis. The consistent features of chromatolysis included the condensation of the cytoplasm and chromatin, cell shrinkage, formation of “chromatin balls,” intact normal organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s, and fragmentation of cells observed by the budding of fragments enclosed in the cell membrane. These budding fragments were termed “apoptotic bodies,” thus coining the name “apoptosis” to describe this form of cell death. The authors of these studies, most likely unfamiliar with older publications on chromatolysis, were essentially describing a process identical to chromatolysis.
Central Chromatolysis
Central chromatolysis is the most common form of chromatolysis and is characterized by the loss or dispersion of the Nissl bodies starting in the center of the neuron (around the nucleus) and then extending peripherally towards the plasma membrane.Peripheral Chromatolysis
Peripheral chromatolysis is much less common, but has been reported to occur after axotomy and ischemia in certain species. Peripheral chromatolysis is essentially the reverse of central chromatolysis, in which the disintegration of Nissl bodies is initiated at the periphery of the neuron and extends inwards towards the nucleus of the cell. Peripheral chromatolysis has been observed to occur in lithium-induced chromatolysis and it could be useful in investigating and countering the hypothesis that waves of enzymatic activity always progress from the perinuclear area to the peripheral of the cell.Nissl Bodies
Studies have shown that injury to spinal motor neurons results in increased size of the nucleolusNucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
, nucleus, and cell body. The nucleus becomes elongated and organization of Nissl bodies is disrupted. The process of Nissl dissolution is less apparent toward periphery of the cell body of the neuron, where normal-looking Nissl bodies may be present. This loss of Nissl bodies propagating from the center of the cell body outward is known as central chromatolysis. In neurons receiving axonal transection, central chromatolysis is observed in the area between the nucleus and the axon hillock following.
The enlargement of nuclear components due to axotomy can be explained by the alteration of the cell’s cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
. The cytoskeleton maintains the nuclear components of a cell and the size of the cell body in neurons. The increase in protein within the neuron leads to this change in the cytoskeleton. The increase in protein can be explained by the increase in cytoskeleton size. Changes in the cell body cytoskeleton seem to be responsible for enhanced nuclear eccentricity following axonal injury.
One hypothesis behind the incidence of chromatolysis following axotomy is that the shortening of the axon prevents the incorporation of the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
al cytoskeleton that undergoes formation in the injured neuron. Nuclear eccentricity can be attributed to the presence of excess axonal cytoskeleton between the nucleus and axon hillock, which causes chromatolysis. A second hypothesis proposes that blockage of axonal cytoskeletal proteins causes chromatolysis.
Central chromatolysis is the loss of basophilic staining after axotomy. The loss of staining begins near the nucleus and spreads toward the axon hillock. The basophilic rim is formed as chromatolysis compresses the cytoplasmic skeleton.
Acrylamide Intoxication
Acrylamide intoxication has been shown to be an agent for the induction of chromatolysis. In one study groups of rats were injected with acrylamideAcrylamide
Acrylamide is a chemical compound with the chemical formula C3H5NO. Its IUPAC name is prop-2-enamide. It is a white odourless crystalline solid, soluble in water, ethanol, ether, and chloroform. Acrylamide is incompatible with acids, bases, oxidizing agents, iron, and iron salts...
for 3, 6, and 12 days and the A- and B-cell perikarya of their L5 dorsal root ganglion
Dorsal root ganglion
In anatomy and neuroscience, a dorsal root ganglion is a nodule on a dorsal root that contains cell bodies of neurons in afferent spinal nerves.-Unique unipolar structure:...
were examined. There was no morphological change in the B-cell perikarya, the A-cell perikarya however exhibited chromatolysis in 11% and 23% of the population, for the 6 and 12 days groups respectively. Acrylamide intoxication resembles neural axotomy histologically and mechanically. In each case the neuron undergoes chromatolysis and atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
of the cell body and axon. Also both seem to be mechanically related to a disruption of the delivery of neurofilament to the axon due to a decreased transport of a trophic factor from the axon to the cell body.
Amyotrophic Lateral Sclerosis (ALS)
Central chromatolysis has been observed in anterior horn neurons of patients with amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(ALS). Patients with ALS appear to have significant alterations that occur within the chromatolyzed neuronal cells. These alterations include dense conglomerates of aggregated dark mitochondria and presynaptic vesicles, bundles of neurofilament
Neurofilament
Neurofilaments are the 10 nanometer intermediate filaments found specifically in neurons. They are a major component of the cell's cytoskeleton, and provide support for normal axonal radial growth...
s, and a marked increase of presynaptic vesicles. Changes to the function of the motor neurons have also been observed. The most typical functional change in chromatolytic motor neurons is the significant reduction in size of the monosynaptic excitatory postsynaptic potentials (EPSPs). These monosynaptic EPSPs also seem to be prolonged in the chromatolyzed cells of ALS patients. This functional change to the anterior horn neurons could result in the elimination of certain excitatory synaptic inputs and thus give rise to the clinical motor function impairment that is characteristic of the ALS disease.
Idiopathic Brainstem Neuronal Chromatolysis
Severe neuronal chromatolysis has been detected in the brainstems of adult cattle with the neurodegenerative condition known as idiopathic brainstem neuronal chromatolysis (IBNC). The disease has a significant correlation with abnormal labeling for prion protein (PrP) in the brain. IBNC has also been characterized by severe neuronal, axonAxon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
al, and myelin degradation, accompanied by non-supportive inflammation and changes in spongiform of various regions of grey matter. A significant loss of neurons due to hippocampal degeneration has also been observed. The degenerate chromatolysis neurons seldom showed intracytoplasmic labeling for PrP.