GnRH-secreting neuron dysfunction recognized in Down syndrome.
Current research has actually revealed that the neurons that launch the hormone referred to as gonadotropin-releasing hormone (GnRH), which is known to manage recreation via the hypothalamus, may also run on other brain locations that might be associated with other functions, such as cognition.
Due to this, the Lille Neuroscience & & Cognition lab team under the instructions of Vincent Prévot, Inserm Research Director, examined the mechanism managing GnRH in mouse models of Down syndrome.
The lab demonstrated that 5 strands of microRNA managing the production of this hormonal agent– which are found on chromosome 21– are inefficient. This supernumerary chromosome then results in abnormalities in the nerve cells that produce GnRH. These findings were verified at both cellular and genetic levels. The Inserm researchers were able to demonstrate that the progressive cognitive and olfactory deficiencies seen in the mice were closely connected to dysfunctional GnRH secretion.
Bring back GnRH production to restore cognitive function.
The Inserm scientists were then able to demonstrate that restoring physiological GnRH system function brings back cognitive and olfactory functions in trisomic mice.
These findings in mice were discussed with Nelly Pitteloud, teacher at the Faculty of Biology and Medicine of the University of Lausanne and head of the Endocrinology, Diabetology, and Metabolism Department at CHUV. Her research study focuses on genetic GnRH shortage, an uncommon disease which manifests by the absence of spontaneous the age of puberty. These patients are given pulsatile GnRH treatment in order to recreate the natural pulsatile rhythm of this hormonal agents secretion, in order to induce puberty.
The scientists therefore decided to test the efficacy of pulsatile GnRH therapy on cognitive and olfactory deficits in trisomic mice, following a protocol similar to that used in humans. After 15 days, the group had the ability to demonstrate the restoration of cognitive and olfactory functions in mice.
Pulsatile GnRH therapy enhances cognitive function and neural connection in a little patient group.
The next stage for the doctors and researchers included a pilot medical trial in patients to examine the impacts of this treatment. 7 guys with Down syndrome, in between 20 and 50 years of age, received one subcutaneous dose of GnRH every 2 hours for 6 months by means of a pump put on the arm. Cognition and olfactory tests along with MRI exams were carried out before and after the treatment.
From the scientific perspective, cognitive performance increased in 6 of the 7 clients with much better three-dimensional representation, better understanding of guidelines, improved thinking, attention, and episodic memory. However, the treatment had no effect on the capability to smell. These measures to enhance cognitive functions were validated by brain imaging carried out by the CHUV Department of Clinical Neurosciences, which revealed a considerable increase in functional connectivity.
These data recommend that the treatment acts on the brain by enhancing the communication between certain areas of the cortex. “Maintaining the GnRH system appears to play a crucial role in brain maturation and cognitive functions,” describes Prévot. “In Down syndrome, pulsatile GnRH treatment is looking appealing, especially as it is an existing treatment without any substantial side results,” includes Pitteloud.
These promising findings now justify the launch of a bigger research study– with the addition of women– to verify the effectiveness of this treatment in people with Down syndrome, but likewise for other neurodegenerative conditions such as Alzheimers disease.
Reference: “GnRH replacement saves cognition in Down syndrome” by Maria Manfredi-Lozano, Valerie Leysen, Michela Adamo, Isabel Paiva, Renaud Rovera, Jean-Michel Pignat, Fatima Ezzahra Timzoura, Michael Candlish, Sabiha Eddarkaoui, Samuel A. Malone, Mauro S. B. Silva, Sara Trova, Monica Imbernon, Laurine Decoster, Ludovica Cotellessa, Manuel Tena-Sempere, Marc Claret, Ariane Paoloni-Giacobino, Damien Plassard, Emmanuelle Paccou, Nathalie Vionnet, James Acierno, Aleksandra Maleska Maceski, Antoine Lutti, Frank Pfrieger, S. Rasika, Federico Santoni, Ulrich Boehm, Philippe Ciofi, Luc Buée, Nasser Haddjeri, Anne-Laurence Boutillier, Jens Kuhle, Andrea Messina, Bogdan Draganski, Paolo Giacobini, Nelly Pitteloud and Vincent Prevot, 2 September 2022, Science.DOI: 10.1126/ science.abq4515.
A pilot research study using 7 clients to investigate GnRH pulsatile injection treatment was brought out. The Inserm scientists were able to show that the progressive cognitive and olfactory shortages seen in the mice were carefully connected to inefficient GnRH secretion.
Seven men with Down syndrome, in between 20 and 50 years of age, got one subcutaneous dosage of GnRH every 2 hours for 6 months by means of a pump put on the arm. “Maintaining the GnRH system appears to play an essential role in brain maturation and cognitive functions,” explains Prévot. “In Down syndrome, pulsatile GnRH therapy is looking promising, especially as it is an existing treatment with no significant side effects,” includes Pitteloud.
There are a variety of signs related to Down syndrome (DS), which is triggered by trisomy of chromosome 21, including intellectual special needs and olfactory loss.
A brand-new treatment has been shown to improve cognitive function..
In order to boost the cognitive capabilities of a little sample of Down syndrome clients, an Inserm group at the Lille Neuroscience & & Cognition laboratory (Inserm/Universit é de Lille, Lille University Hospital) has actually collaborated with their equivalents at Lausanne University Hospital (CHUV). Initially, the scientists exposed the dysfunction of the GnRH neurons in an animal model of Down syndrome and its ramifications for the conditions cognitive function impairment.
A pilot study using seven patients to investigate GnRH pulsatile injection treatment was carried out. The findings were encouraging: the treatment increased cognitive function and brain connection. The findings were just recently published in the journal Science..
Down syndrome, likewise referred to as trisomy 21, impacts around one in every 800 births and triggers a range of medical symptoms, including cognitive impairment. 77% of individuals who have the condition have symptoms that resemble those of Alzheimers illness as they end up being older. It is also regular to have a progressive loss of scent starting in the prepubertal duration, with potential sexual maturation deficits occurring in males. This is common in neurodegenerative diseases.
