New research points to potential treatment for memory loss activating a protein dysregulated in dementia

Researchers at the Universitat Autònoma de Barcelona have discovered a new molecular mechanism which regulates the formation of associative memory in the hippocampus, a region of the brain profoundly affected in the initial stages of some neurodegenerative diseases such as Alzheimer's disease. The study, directed by Carlos Saura from the Institute of Neurosciences of the Universitat Autònoma de Barcelona, is featured in this month's edition of the scientific journal Biological Psychiatry.

Associative memory is necessary to relate and remember situations, places and people at long term and is one of the cognitive functions affected by cases of dementia, such as Alzheimer's disease. This new study shows that a protein called CRTC1, which regulates genes essential for neuron function, needs to be activated in the hippocampus so that associative memory can be processed and stored.

In previous studies, the research group demonstrated that CRTC1 was disrupted in the brain of Alzheimer´s patients at early disease stages. The new study reveals that disruption of CRTC1 function also occurs while neurodegeneration is occurring.

To restore CRTC1 function, researchers used a gene therapy approach to introduce copies of this gene in a group of neurons in the hippocampus of a mouse model of neurodegeneration. Mice which already have memory deficits and neuropathology and treated with this gene-therapy approach were able to remember a negative experience they had in the past. Mice which received an innocuous treatment did not remember the experience and behaved normally. According to Carlos Saura, “The relevance of this discovery is that activation of specific neurons of the hippocampus reverses memory loss even at late stages of neurodegeneration”.

The research is this month's featured article in the prestigious psychiatry journal Biological Psychiatry and represents an important advance in what is known about molecular mechanisms involved in the formation and loss of memory taking place in various neurodegenerative diseases. “These results are exciting since they provide strong support for potential translational applications in the clinic because this molecular mechanism could be a new target to reverse memory decline in dementia”, said Dr Carlos Saura.

Original article:
Parra-Damas A., Chen M., Enríquez-Barreto L., Ortega L., Acosta S., Camats Perna J., Fullana N., Aguilera J., Rodríguez-Alvarez J., and Saura C.A. CRTC1 function during memory encoding is disrupted in neurodegeneration (2017). Biol Psychiatry 81 (2): 111-123