Pharmacological Stimulation of the Brain Serotonin Receptor 7 as a Novel Therapeutic Approach for Rett Syndrome

Abstract Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene, characterized by severe behavioral and physiological impairments for which no cure is available. The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25 mg/kg/day for 7 days) was proved to rescue neurobehavioral alterations in a mouse model of RTT. In the present study, we aimed at gaining insight into the mechanisms underpinning the efficacy of 5-HT7R pharmacological stimulation by investigating its epigenetic outcomes in the brain of RTT female mice bearing a truncating MeCP2 mutation. Treatment with LP-211 normalized the reduced histone H3 acetylation and HDAC3/NCoR levels, and increased HDAC1/Sin3a expression in RTT mouse cortex. Repeated 5-HT7R stimulation also appeared to strengthen the association between NCoR and MeCP2 in the same brain region. A different profile was found in RTT hippocampus, where LP-211 rescued H3 hyperacetylation and increased HDAC3 levels. Overall, the present data highlight a new scenario on the relationship between histone acetylation and serotoninergic pathways. 5-HT7R is confirmed as a pivotal therapeutic target for the recovery of neuronal function supporting the translational value of this promising pharmacological approach for RTT.

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Rescue of prepulse inhibition deficit and brain mitochondrial dysfunction by pharmacological stimulation of the central serotonin receptor 7 in a mouse model of CDKL5 Deficiency Disorder

Neuropharmacology ◽

10.1016/j.neuropharm.2018.10.018 ◽

2019 ◽

Vol 144 ◽

pp. 104-114 ◽

Cited By ~ 11

Author(s):

Daniele Vigli ◽

Laura Rusconi ◽

Daniela Valenti ◽

Paolo La Montanara ◽

Livia Cosentino ◽

...

Keyword(s):

Mouse Model ◽

Mitochondrial Dysfunction ◽

Prepulse Inhibition ◽

Serotonin Receptor ◽

Pharmacological Stimulation ◽

Stimulation Of

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Relationship between behavioural response to amphetamine and propensity to develop stereotypic behaviour in pigs

Proceedings of the British Society of Animal Production (1972) ◽

10.1017/s0308229600020092 ◽

1991 ◽

Vol 1991 ◽

pp. 58-58

Author(s):

E M C Terlouw ◽

A B Lawrence ◽

A W lllius

Keyword(s):

Motor Activity ◽

Standard Dose ◽

Large Individual ◽

Excessive Drinking ◽

Brain Dopamine ◽

Pharmacological Stimulation ◽

Stereotypic Behaviour ◽

The Brain ◽

Stimulation Of

The dopamine systems In the brain are strongly involved in motor activity. Pharmacological stimulation of brain dopamine systems with dopamine agonists initially results in increased levels of motor activity that with increasing doses become more stereotyped in form. It has been suggested that in tethered sows, stereotypies develop because chronic environmental stress produces activation of brain dopamine systems (Dantzer, 1986). Furthermore, differences In the sensitivity of brain dopamine systems may form the basis of the large individual variation found in level of stereotypies (Segal and Kuczenski, 1987). Manipulation of the chain forms the major category of stereotypic behaviour during long term tethering. In addition, many pigs develop excessive drinking (Terlouw et al., in press). The present study investigated whether female nulliparous pigs differed in their response to a standard dose of amphetamine and whether this response is correlated to the amount of chain activity and drinking that developed during subsequent long term tethering.

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A Novel Therapeutic Approach for Treating Rett Syndrome.

10.46940/snnsj.03.1009 ◽

2021 ◽

pp. 1-6

Keyword(s):

Effective Treatment ◽

Rett Syndrome ◽

Pervasive Developmental Disorder ◽

Therapeutic Approach ◽

Developmental Disorder ◽

Term Treatment ◽

Short Term Treatment ◽

Typical Finding ◽

One Step ◽

Novel Therapeutic

Background: Rett syndrome is a rare X-linked dominant neuro-developmental and pervasive developmental disorder that has no satisfactory or effective treatment. The diagnosis is generally clinical and autistic feature is a typical finding in all patients. We have previously described the short-term treatment of an Iraqi girl with Rett syndrome who was first seen at the age of about three years. The girl was treated with intramuscular cerebrolysin and oral citicoline for 40 days. Treatment was associated with significant improvement with the development of purposeful movement and the ability to hold feeding bottle with assistant of the mother and feed her. She was able to stand and step one step holding furniture. She started babbling and showed some reduction in the autistic features. The aim of this paper is to describe the extended treatment of the girl with Rett syndrome which was treated with a novel therapeutic approach which included intramuscular cerebrolysin, citicoline and piracetam. Patients and methods: After the initial 40 days treatment, the girl received several treatment courses that included intramuscular cerebrolysin, citicoline and piracetam. Results: Several months of treatment resulted in improvements in behavior, autistic features and mobility and she was walking confidently holding a wall or furniture. Treatment was not associated with any side effects. Conclusion: Rett syndrome is a very complex neuro-developmental and pervasive developmental disorder that has no satisfactory or effective treatment. The use of novel therapeutic approach which included intramuscular cerebrolysin, citicoline and piracetam for the treatment of Rett syndrome resulted in within few months a significant improvement that have not been reported without treatment or with any other therapies before.

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