Title : Can we stimulate neuroplasticity with the cell signaling molecule ghrelin?
The increase in human lifespan during the last century is accompanied by an increased risk for development of age-related disorders including neurodegenerative diseases (NDD) such as Alzheimer’s and Parkinson’s disease. These pathologies are characterised by impairment of synaptic activity and plasticity, and loss of neurons in motor, sensory and cognitive systems. The neuropeptide and gastric hormone ghrelin has a very promising therapeutic potential for treatment of NDD with its ability to stimulate the repair and activity of neurons. Therefore, we subjected cultured cerebral and cerebellar cortex neurons, and organotypic cortical slices from rat brains to hypoxia for 6 hours, followed by 24 hours normoxya and treatment with ghrelin. We further quantitatively analyzed immunostainings for ghrelin’s receptor (GHSR1), synaptic marker synaptophysin and transcription factor Pax6, a regulator of neural progenitor cell fate. In the cortex, hypoxia down-regulated Pax6 levels, increased GHSR1 expression and its internalization into the nucleus. Additionally, hypoxia drastically reduced the number of synapses. Ghrelin supplementation of the culture medium during the recovery period normalized the expression levels of Pax6 and GHSR1, and significantly elevated synapse density, as compared with the control cultures or with the pre-hypoxic levels. Our findings suggest that ghrelin stimulates neurogenic factors in non-neurogenic brain areas and stimulates synaptic plasticity, both extremely important for protection against neurodegeneration and accompanying dementia.
What will audience learn from your presentation?
- Our study provides some new insights about the mechanisms of ghrelin’s neuroprotective effect against neuronal damage.
- This information opens avenues for development of new diagnostic and therapeutic approaches to the neurodegenerative diseases manifested with impaired neuronal and synaptic plasticity.
- We hope that our results will have a significant clinical relevance and could be used as a platform for other labs and universities to expand their research or teaching.