Gene Therapy Enhances Object Recognition Memory in Young and Old Mice

Researchers here report on a gene therapy to upregulate RGS14 expression in an area of the brain associated with object recognition, showing that it enhances function in both old and young mice. Given past studies of RSG14, this is an expected result. Interestingly, increased RSG14 expression appears to produce benefits via upregulation of BDNF expression, a change that is is known to increase neurogenesis. Neurogenesis is the creation of new neurons and their integration into existing neural networks, necessary for memory function, as well as for maintenance of the brain more generally. Increased neurogenesis in adult life has been shown to produce numerous benefits in animal studies, with no obvious downsides.

Memory deficit, which is often associated with aging and many psychiatric, neurological, and neurodegenerative diseases, has been a challenging issue for treatment. Up till now, all potential drug candidates have failed to produce satisfactory effects. Therefore, in the search for a solution, we found that a treatment with the gene corresponding to the RGS14414 protein in visual area V2, a brain area connected with brain circuits of the ventral stream and the medial temporal lobe, which is crucial for object recognition memory (ORM), can induce enhancement of ORM.

In this study, we demonstrated that the same treatment with RGS14414 in visual area V2, which is relatively unaffected in neurodegenerative diseases such as Alzheimer's disease, produced long-lasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer's disease. Furthermore, we found that the prevention of memory deficits was mediated through the upregulation of neuronal arborization and spine density, as well as an increase in brain-derived neurotrophic factor (BDNF). A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer's disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.

These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer's disease. Therefore, our findings of RGS14414 gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.



Based on their 2019 paper (, it looks like the mechanism doesn't involve neurogenesis per se, but an increase of dendrite density and branching in the existing neurons, which goes up from 8 to 15 from the gene therapy. By contrast, humans already have dendrites which are considerably more complex than mice, with dendritic lengths 3 times longer ( Interestingly, they transfected the mice with the human RGS14 gene, which may be different from the mouse version and cause more dendritic branching, as in humans. This also may explain the divergent results from other research on RGS14 (see

But at the end of the day, this would mean we're looking at low-hanging fruit that human evolution has already picked. Also, it doesn't seem that this directly increases BDNF, as the effect on BDNF tapers off once dendritic arborization occurs, as noted at the end of their paper. It seems more likely this stimulates dendrite growth, which in turn requires and therefore stimulates BDNF production. But if we already have the number of dendrites it would produce, it won't stimulate much BDNF for side neurogenesis..

Posted by: Aryeh Holzer at December 28th, 2023 9:13 AM
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