UCI neurobiologists restore youthful vigor to adult brains

brainplasticity

Reactivated plasticity points to new treatments for developmental disorders

They say you can’t teach an old dog new tricks. The same can be said of the adult brain. Its connections are hard to change, while in children, novel experiences rapidly mold new connections during critical periods of brain development.

UC Irvine neurobiologist Sunil Gandhi and colleagues wanted to know whether the flexibility of the juvenile brain could be restored to the adult brain. Apparently, it can: They’ve successfully re-created a critical juvenile period in the brains of adult mice. In other words, the researchers have reactivated brain plasticity – the rapid and robust changes in neural pathways and synapses as a result of learning and experience.

And in doing so, they’ve cleared a trail for further study that may lead to new treatments for developmental brain disorders such as autism and schizophrenia. Results of their study appear online in Neuron.

The scientists achieved this by transplanting a certain type of embryonic neuron into the brains of adult mice. The transplanted neurons express GABA, a chief inhibitory neurotransmitter that aids in motor control, vision and many other cortical functions.

Much like older muscles lose their youthful flexibility, older brains lose plasticity. But in the Gandhi study, the transplanted GABA neurons created a new period of heightened plasticity that allowed for vigorous rewiring of the adult brain. In a sense, old brain processes became young again.

In early life, normal visual experience is crucial to properly wire connections in the visual system. Impaired vision during this time leads to a long-lasting visual deficit called amblyopia. In an attempt to restore normal sight, the researchers transplanted GABA neurons into the visual cortex of adult amblyopic mice.

“Several weeks after transplantation, when the donor animal’s visual system would be going through its critical period, the amblyopic mice started to see with normal visual acuity,” said Melissa Davis, a postdoctoral fellow and lead author of the study.

These results raise hopes that GABA neuron transplantation might have future clinical applications. This line of research is also likely to shed light on the basic brain mechanisms that create critical periods.

“These experiments make clear that developmental mechanisms located within these GABA cells control the timing of the critical period,” said Gandhi, an assistant professor of neurobiology & behavior.

He added that the findings point to the use of GABA cell transplantation to enhance retraining of the adult brain after injury. Furthermore, this work sparks new questions as to how these transplanted GABA neurons reactivate plasticity, the answers to which might lead to therapies for currently incurable brain disorders.

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Scientists Identify the Signature of Aging in the Brain

Immunofluorescence microscope image of the choroid plexus. Epithelial cells are in green and chemokine proteins (CXCL10) are in red

Immunofluorescence microscope image of the choroid plexus. Epithelial cells are in green and chemokine proteins (CXCL10) are in red

Weizmann Institute researchers suggest that the brain’s “immunological age” is what counts

How the brain ages is still largely an open question – in part because this organ is mostly insulated from direct contact with other systems in the body, including the blood and immune systems. In research that was recently published in Science, Weizmann Institute researchers Prof. Michal Schwartz of the Neurobiology Department and Dr. Ido Amit of Immunology Department found evidence of a unique “signature” that may be the “missing link” between cognitive decline and aging. The scientists believe that this discovery may lead, in the future, to treatments that can slow or reverse cognitive decline in older people.

Until a decade ago, scientific dogma held that the blood-brain barrier prevents the blood-borne immune cells from attacking and destroying brain tissue. Yet in a long series of studies, Schwartz’s group had shown that the immune system actually plays an important role both in healing the brain after injury and in maintaining the brain’s normal functioning. They have found that this brain-immune interaction occurs across a barrier that is actually a unique interface within the brain’s territory.

This interface, known as the choroid plexus, is found in each of the brain’s four ventricles, and it separates the blood from the cerebrospinal fluid. Schwartz: “The choroid plexus acts as a ‘remote control’ for the immune system to affect brain activity. Biochemical ‘danger’ signals released from the brain are sensed through this interface; in turn, blood-borne immune cells assist by communicating with the choroid plexus.This cross-talk is important for preserving cognitive abilities and promoting the generation of new brain cells.”

This finding led Schwartz and her group to suggest that cognitive decline over the years may be connected not only to one’s “chronological age” but also to one’s “immunological age,” that is, changes in immune function over time might contribute to changes in brain function – not necessarily in step with the count of one’s years.

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