Antidepressants enhance neuronal plasticity in the visual system

In the April 18 issue of Science, scientists from the Scuola Normale Superiore in Pisa, Italy and the Neuroscience Centre at the University of Helsinki, Finland, provide new information about the mechanism of action of antidepressant drugs. In addition, the study suggests that antidepressants could also be used for the treatment of amblyopia. However, to produce a functional effect, antidepressant treatment also seems to require environmental stimuli, such as rehabilitation or therapy.

According to Professor Eero Castrén at the University of Helsinki, the original objective of the study was to learn more about why the antidepressant effect of fluoxetine (also known as Prozac) and other selective serotonin reuptake inhibitors develops so slowly, many weeks after starting treatment.

Castrén’s research group has approached this question by examining the growth factor, brain-derived neurotrophic factor (BDNF), which influences plasticity of the nervous system or in other words, the ability of brain cells to change their structure or function in response to stimuli. Antidepressants seem to act through BDNF, thus enhancing the plasticity of the nervous system, at least in certain brain areas. However, it has been unclear how antidepressant-induced increases in BDNF could relieve depression.

Neuronal plasticity of the developing visual cortex has been well characterised. Therefore, this classical model of the visual cortex was utilised to examine the effect of fluoxetine on neuronal plasticity, although there was previously no evidence that antidepressants would act on the visual system. During early childhood, if one eye remains weaker than the other eye, the neuronal connections of the stronger eye take over the visual cortex while the connections of the weaker eye retract. During a critical period of early childhood, neuronal connections are in a highly plastic state, and the vision of the weaker eye can be strengthened by covering the better eye, thus reinforcing the connections of the weaker eye to the visual cortex. In adolescence however, after the critical period has closed, plasticity is reduced and covering the better eye no longer strengthens the connections of the weaker eye which remains poor in vision throughout adulthood.

The experiments, mainly conducted by the research group of Professor Lamberto Maffei in Pisa, showed that treatment with the antidepressant, fluoxetine reopened the critical period of plasticity in the visual cortex of adult rats. In experiments where one eye of a young rat was covered during the critical period and reopened only in adulthood, vision improved in the weaker eye to finally equal that of the healthy eye when fluoxetine treatment was combined with covering the healthy eye. This fluoxetine-induced enhancement of plasticity was associated with increased BDNF and reduced cortical inhibition in the visual cortex, which advanced reorganisation of the neuronal connections.

Since fluoxetine, when combined with covering the better eye, improved vision in the weaker eye of adult rats, it is possible that antidepressants could be similarly used in amblyopic humans. The results suggest that the improved plasticity induced by antidepressants leads to a functional neuronal reorganisation in the cerebral cortex. The ability of an antidepressant to facilitate the reorganisation of neuronal connections in a brain area not associated with mood, suggests that similar treatment strategies might also be useful in the treatment of other brain disorders.

It is important to note that fluoxetine improved vision in the weaker eye only if the better eye was covered. This suggests that while antidepressants provide the possibility of rearranging cortical connections, environmental stimuli are required to guide the rearrangement to produce the desired effect.

It is possible that defective neuronal connections in cortical areas related to mood regulation might predispose people to depression. The enhanced plasticity provided by the antidepressant might allow reorganisation of cortical connections and function. However, Castrén emphasises that antidepressants do not repair the network on their own, but that functional recovery also requires environmental guidance, such as social interaction, rehabilitation or therapy.

Source: University of Helsinki

Related stories:

Trigger for brain plasticity identified
Researchers have long sought a factor that can trigger the brain's ability to learn – and perhaps recapture the "sponge-like" quality of childhood. In the August 8 issue of the journal Cell, neuroscientists at Children's Hospital Boston report that they've identified such a factor, a protein called Otx 2.
Study suggests caution on a new anti-obesity drug in children
A new class of anti-obesity drugs that suppresses appetite by blocking cannabinoid receptors in the brain could also suppress the adaptive rewiring of the brain necessary for neural development in children, studies with mice have indicated. One such drug, rimonabant (trade name Acomplia) has been developed by Sanofi-Aventis and is awaiting approval for use in the U.S., and other pharmaceutical companies are developing similar drugs.
MIT reports key pathway in synaptic plasticity
Scientists are keenly studying how neurons form synapses--the physical and chemical connections between neurons--and the "pruning" of neural circuits during development, not least because synaptic abnormalities may partially underlie many developmental and neurodegenerative diseases.
Study Provides Insight Into How the Brain Loses Plasticity of Youth
A protein once thought to play a role only in the immune system could hold a clue to one of the great puzzles of neuroscience: how do the highly malleable and plastic brains of youth settle down into a relatively stable adult set of neuronal connections? Harvard Medical School researchers report in the August 17 Science Express that adult mice lacking the immune system protein paired-immunoglobulin like receptor-B (PirB) had brains that retained the plasticity of much younger brains, suggesting that PirB inhibits such plasticity.
Boston University partners in NSF challenge to create wireless network using visible light
Boston University's College of Engineering is a partner launching a major program, under a National Science Foundation grant, to develop the next generation of wireless communications technology based on visible light instead of radio waves. Researchers expect to piggyback data communications capabilities on low-power light emitting diodes, or LEDs, to create "Smart Lighting" that would be faster and more secure than current network technology.
Jott transcribes cell calls to text
Never before have we been so connected to each other. When it comes to instant personal communication these days, the cell phone and the Internet are how we do it. A mere century ago, our options to communicate with each other were limited mostly to writing letters, using carrier pigeons, sending the occasional smoke signal, drums, messengers - you get the idea.
Iron-moving malfunction may underlie neurodegenerative diseases, aging
A glitch in the ability to move iron around in cells may underlie a disease known as Type IV mucolipidosis (ML4) and the suite of symptoms—mental retardation, poor vision and diminished motor abilities—that accompany it, new research at the University of Michigan shows.
Hallucinations in the flash of an eye
Dominic H. ffytche at the Institute of Psychiatry in London reviews what we do know and moves the field forward, by introducing a new experimental approach to studying hallucinations as they occur.

News discussion:

Medicine & Health news