Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome.
Livia Cosentino, Chiara Urbinati, Chiara Lanzillotta and 12 others
PMID 39300547WHAT IT FOUND
In symptomatic female Rett syndrome mice, rimonabant normalized a mitochondrial CB1 receptor pathway, restored brain ATP production, reduced blood oxidative stress, and improved spatial memory.
It impaired memory in wild-type mice and was not tested in humans.
Key findings
01In symptomatic female Rett syndrome mice, rimonabant lowered mitochondrial CB1 receptor overexpression and increased mitochondrial PKA activity in brain mitochondria.
02Rimonabant restored brain ATP production and reduced blood oxidative stress in these mice.
03Rimonabant improved spatial memory in Rett mice but impaired spatial memory in wild-type mice.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study was done in mice, not people, so it cannot show what rimonabant would do in a patient with Rett syndrome. Group sizes were small: N=3-6 for biochemical outcomes and N=5-8 for behavioural outcomes. The article does not report how mice were assigned to rimonabant or vehicle. Rimonabant impaired spatial memory in wild-type mice, so the drug effect was not uniformly beneficial. The authors say they cannot exclude that benefits came from changes in total CB1R rather than mitochondrial CB1R alone. The study used whole brain measures and did not test whether effects differ by brain region.
Declared interests
Funder named: Ministero dell’Università e della Ricerca and Ministero della Salute. The supplied text does not report other conflicts of interest.
The easy way to misread this
Do not conclude that rimonabant is a treatment for people with Rett syndrome. The study was in mice, used a drug not given to patients here, and rimonabant impaired spatial memory in wild-type mice.