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Просмотр полной версии : SSRI antidepressants and neuronal plasticity (Science)



CopperKettle
26.04.2008, 07:01
A short review at Schizophrenia Research Forum:

Prozac and Plasticity—Antidepressant’s Action an Eye Opener (http://www.schizophreniaforum.org/new/detail.asp?id=1432)


25 April 2008. Selective serotonin reuptake inhibitors such as fluoxetine (better known as Prozac) have always been a bit of a puzzle. Though they quickly elevate serotonin levels, it can take weeks for these drugs to have a noticeable antidepressant effect. Research from the past decade suggests that these drugs have a much more profound and gradual mode of action, possibly related to increased synthesis of new neurons and new neural connections.

In last week’s Science, researchers led by Jose Maya Vetencourt and Lamberto Maffei at the Institute for Neuroscience, National Research Council, Pisa, Italy, collaborating with Eero Castrén's group at the University of Helsinki, reported that antidepressants do, indeed, induce changes in neuronal connections and that these neural rearrangements are functionally significant. They found that antidepressants can...

There's also a short Q&A session with one of the authors, Eero Castrén.

Reference:
Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O’Leary OF, Castren E, Maffei L. The antidepressant fluoxetine restores plasticity in the adult visual cortex (http://www.ncbi.nlm.nih.gov/pubmed/18420937?dopt=Abstract). Science April 18, 2007;320:385-388.


We investigated whether fluoxetine, a widely prescribed medication for treatment of depression, restores neuronal plasticity in the adult visual system of the rat. We found that chronic administration of fluoxetine reinstates ocular dominance plasticity in adulthood and promotes the recovery of visual functions in adult amblyopic animals, as tested electrophysiologically and behaviorally. These effects were accompanied by reduced intracortical inhibition and increased expression of brain-derived neurotrophic factor in the visual cortex. Cortical administration of diazepam prevented the effects induced by fluoxetine, indicating that the reduction of intracortical inhibition promotes visual cortical plasticity in the adult. Our results suggest a potential clinical application for fluoxetine in amblyopia as well as new mechanisms for the therapeutic effects of antidepressants and for the pathophysiology of mood disorders.

Discussion in the Russian language section:
СИОЗС-антидепрессанты и нейрональная пластичность (http://forum.neuroscience.ru/showthread.php?t=2238)

This Week in Science (http://www.sciencemag.org/cgi/content/full/sci;320/5874/285l)

The mechanism of action of antidepressant drugs is still unclear, but neuronal plasticity may be important. Maya Vetencourt et al. (p. 385 (http://www.sciencemag.org/cgi/content/short/320/5874/385)) investigated whether chronic treatment with antidepressants restores plasticity in the adult visual system of the rat. The authors used two classical models of plasticity, the ocular dominance shift of visual cortical neurons following monocular deprivation and the recovery of visual function in the adult after long-term monocular deprivation. Surprisingly, chronic administration of antidepressants increased brain-derived neurotrophic factor expression in the visual cortex and reduced intracortical inhibition, thus restoring ocular dominance plasticity in adulthood and promoting the recovery of vision in adult rats. Antidepressants may thus increase plasticity throughout the brain, potentially explaining their antidepressant effects.

Science 18 April 2008:
Vol. 320. no. 5874, p. 285
DOI: 10.1126/science.320.5874.285l

summer
26.04.2008, 08:38
Amblyopia, or lazy eye, is a disorder of the visual system that is characterized by poor or indistinct vision in an eye that is otherwise physically normal, or out of proportion to associated structural abnormalities. It has been estimated to affect 1–5% of the population.

The problem is caused by either no transmission or poor transmission of the visual image to the brain for a sustained period of dysfunction or during early childhood. Amblyopia normally only affects one eye, but it is possible to be amblyopic in both eyes if both are similarly deprived of a good, clear visual image. Detecting the condition in early childhood increases the chance of successful treatment.

Physiology

Amblyopia is a developmental problem in the brain, not an organic problem in the eye (although organic problems can induce amblyopia which persist after the organic problem has resolved). The part of the brain corresponding to the visual system from the affected eye is not stimulated properly, and develops abnormally. This has been confirmed via direct brain examination. David H. Hubel and Torsten Wiesel won the Nobel Prize in Physiology or Medicine in 1981 for their work demonstrating the irreversible damage to ocular dominance columns produced in kittens by sufficient visual deprivation during the so-called "critical period". The maximum critical period in humans is from birth to two years old.

Symptoms

Many people with amblyopia, especially those who are only mildly so, are not even aware they have the condition until tested at older ages, since the vision in their stronger eye is normal. However, people who have severe amblyopia may experience associated visual disorders, most notably poor depth perception. Amblyopes may suffer from poor spatial acuity, low sensitivity to contrast and some "higher-level" deficits to vision such as reduced sensitivity to motion. These deficits are usually specific to the amblyopic eye, not the unaffected "fellow" eye. Amblyopes also suffer from problems of binocular vision such as limited stereoscopic depth perception and usually have difficulty seeing the three-dimensional images in hidden stereoscopic displays such as autostereograms. However perception of depth from monocular cues such as size, perspective, and motion parallax is normal.

http://en.wikipedia.org/wiki/Amblyopia

CopperKettle
26.04.2008, 08:47
David H. Hubel and Torsten Wiesel won the Nobel Prize in Physiology or Medicine in 1981 for their work demonstrating the irreversible damage to ocular dominance columns produced in kittens by sufficient visual deprivation during the so-called "critical period".

Yeah, heard about that peculiar period in felines. Never knew it brought a Nobel. Poor kitties.

summer
26.04.2008, 08:56
Yeah, heard about that peculiar period in felines. Never knew it brought a Nobel. Poor kitties.

Well, phenomenon is not feline-specific. Actually, this Wikipedia entry describes similar feature in human beings. It didn't get a Nobel yet. :) But protective effect of antidepressants may be well worth it.

CopperKettle
26.04.2008, 18:14
An interesting quote concerning the environment enrichment:


Maffei’s lab has previously shown that raising rats in an enriched environment has effects equivalent to those of fluoxetine: an enriched environment enhances plasticity in adult visual cortex and allowed a recovery of an amblyopic eye in adults (Sale et al., 2007 (http://www.schizophreniaforum.org/pap/annotation.asp?powID=117657)).