Anaplasia

Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms (tumors). Sometimes, the term also includes an increased capacity for multiplication.^[1] Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to form backward". It implies dedifferentiation, or loss of structural and functional differentiation of normal cells. It is now known, however, that at least some cancers arise from stem cells in tissues; in these tumors failure of differentiation, rather than dedifferentiation of specialized cells, account for undifferentiated tumors.

Anaplastic cells display marked pleomorphism. The nuclei are characteristically extremely hyperchromatic (darkly stained) and large. The nuclear-cytoplasmic ratio may approach 1:1 instead of the normal 1:4 or 1:6. Giant cells that are considerably larger than their neighbors may be formed and possess either one enormous nucleus or several nuclei (syncytia). Anaplastic nuclei are variable and bizarre in size and shape. The chromatin is coarse and clumped, and nucleoli may be of astounding size. More important, mitoses are often numerous and distinctly atypical; anarchic multiple spindles may be seen and sometimes appear as tripolar or quadripolar forms. Also, anaplastic cells usually fail to develop recognizable patterns of orientation to one another (i.e. they lose normal polarity). They may grow in sheets, with total loss of communal structures, such as gland formation or stratified squamous architecture. Anaplasia is the most extreme disturbance in cell growth encountered in the spectrum of cellular proliferations. ^[2]

Anaplasticity and addiction

Drug addiction refers to the loss of control of an individual over the amount of drugs consumed, as well as seeking of the particular drug and is associated with loss of function in the deep layers of the prefrontal cortex ^[3] . Recently, Pier Vincenzo Piazza and Olivier Manzoni of Neurocentre Magendie in Bordeaux, France have discovered a link between consistent impairment (due to drugs) of synaptic plasticity in the brain and the transition to addiction. The impairment in synaptic plasticity is termed anaplasitcity, and refers to the inability of an individual to counteract the modification which occur in the brain due to drug intake. Synaptic plasticity is necessary for behavior to adapt to its ever-changing environmental requirements. ^[4] Furthermore, this may also explain why some individuals become addicted to a certain drug, while others, even after consistently consuming it do not. In other words, some individuals may have the ability to modify the changes that occur in the brain, while others do not. In fact, it has been shown that in rats, only a small percentage actually become addicted, while the rest maintain a steady dosage of cocaine intake, without becoming addicted to it.

The researchers discovered that rats which are addicted to cocaine are unable to undergo LTD (long-term depression) in the nucleus accumbens . LTD is a form of plasticity where the firing rate and intensity of synapses of specific neurons decreases for a period of time which could last from hours to days. It is believed that LTD allows for flexibility in behavior by allowing the brain to learn new things, and anaplasticity causes an LTD deficit in some individuals which eventually becomes chronic, therefore resulting in transition to addiction. The transition to addiction phase refers to the shift from controlled drug use to compulsive drug taking, which results in loss of control of amount consumed. ^{[5] [6]} Overall, it was found that 40% of rats had no signs of being addicted to cocaine after 50 days of self administration.^[7] Furthermore, during the first week of cocaine use, the synaptic plasticity in the nucleus accumbens was not impaired. Impairment started in week 2, when LTD became suppressed. At around week 8-10, plasticity can still be recovered in rats which intake a controlled dose of cocaine (not addicted) but anaplasitcity occurs in rats which have lost control over dosage. In addition, anaplasitcity causes drug induced stimuli to gain more and more power in controlling behavior because the brain can no longer override these commands (causes inflexible behavior), and so the individual become an addict. ^{[8] [9] [10] [11]}

Cocaine alters dendrites and dendritic spines in the prefrontal cortex of pyramidal cells . ^[12] In rats, these changes are not fully developed until in later stages of cocaine administration. ^[3]

References

1. ^ biology-online dictionary
2. ^ Kumar, Vinay, Abul Abbas, Nelson Fausto, and Richard Mitchell. Robbins Basic Pathology. 8th ed. Philadelphia: Saunders Elsevier, 2007. 176-177.
3. ^ ^{a b} Kasanetz, F et al (2012). "Prefrontal synaptic markers of cocaine addiction-like behavior in rats". Molecular Psychiatry: 1-9. 
4. ^ Kauer, JA; Malenka, RC (2007). "Synaptic plasticity and addiction". Nat Rev Neurosci 8: 844-858. 
5. ^ A.P Association (2000). American Psychiatric Press. 
6. ^ O'Brien, C.P (1997). Science 278 (66). 
7. ^ Kasanetz, F et al (2010). "Transition to addiction is associated with a persistant impairment in synaptic plasticity". Science 328: 1709-1712. 
8. ^ Luscher, C; Malenka RC (2011). "Drug-evoked synaptic plasticity in additcion from molecular changes to circuit remodeling". Neuron 69: 650-663. 
9. ^ Chen, BT; et al (2008). "Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA". Neuron 59: 288-297. 
10. ^ Stuber, GD; et al (2008). "Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons". Science 321: 1690-1692. 
11. ^ Yin, HH; et al (2009). "Dynamic reorganization of striatal circuits during the aquisition and consolidation of a skill". Nat Neurosci 12: 333-341. 
12. ^ Robinson, TE; Gorny G, Mitton E, Kolb B (2001). "Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex.". Synapse 39: 257-266. 

See also

• Hyperplasia
• Neoplasia
• Dysplasia
• Metaplasia

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