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Brain connections: MAP6, a new unexpected actor

The proteins intended to be the guardians of the skeletal of the neuronal cells prove to play a role in the implementation of brain connections. This discovery made by researchers at the Pathophysiology of Cytoskeleton group in a rodent model has potential applications in psychiatry.​​

Published on 30 June 2015
The cytoskeletons of our body are made up of microtubules, which have the particularity of continually assembling and disassembling. Certain proteins are there to halt this dynamic and to stabilize the microtubules. Part of the class of MAPs (microtubule-associated protein), these proteins could soon be demoted.

Indeed, work from the Physiopathology of the Cytoskeleton Group and INSERM have come to contradict this assumption. Their work reveals that MAP6 (also known as STOP) has a minor role in stabilizing microtubules in neuronal cells, and yet it has a major role in a whole other dimension.

« Studies in a rodent model lacking the MAP6 protein demonstrate that this molecule has little impact on the dynamics of neuronal microtubules", explains Annie Andrieux, laboratory director at the Physiopathology of the Cytoskeleton Group. "In contrast, we observed a decrease in brain volume and the alteration of higher mental functions (relational learning and memory, etc.)." This loss of volume does not correspond to a reduction in the number of neurons, but to an atrophy of the white matter, namely the axon bundles which connect the neurons from one zone to another in the brain. "Without MAP6, a number of bundles are affected", says the biologist. "In particular, the connections between the hippocampus and hypothalamus, grouped under the term "
fornix", are absent." By focusing on the disappearance of the fornix, the researchers discovered that MAP6 acts on Semaphorin 3E, a guide molecule responsible for building the fiber bundles. "MAP6 is needed for Semaphorin 3E to do its job", says Annie Andrieux.

Left: brain of a normal mouse. Right: brain of a mouse without MAP6

This role of MAP6, unsuspected by the scientific community until now, could have implications in psychiatry. For example, many mental and behavioral disorders are associated with a reduction in the volume of white matter. Thus, alteration of the fornix has been observed in patients with schizophrenia. "Although there are a priori a very large number of genes (and therefore proteins) at the origin of this disease, we can now imagine a treatment involving a MAP6 regulator", concludes the scientist.

Subiculum (in purple, which belongs to the hippocampal zone) cultured with cells expressing Semaphorin 3E (in green). The latter, a guide molecule, induces the production of axons (in red).

The fornix of the brain is a set of fibers connecting two important structures of the brain in the management of memory and emotions: the hippocampus and the posterior part of the hypothalamus. Gold staining of neuronal bundles on brain slices shows that the posterior portion of the fornix connecting the hypothalamus is truncated in mice invalidated for the MAP6 gene disconnecting these two major regions of the brain.

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