Adrenomedullin increases cAMP accumulation and BDNF expression in rat DRG and spinal motor neurons

Iranian Journal of Basic Medical Sciences, 2021 · DOI: https://doi.org/10.22038/ijbms.2021.54796.12289 · Published: July 1, 2021

Neurology Genetics

Simple Explanation

This study investigates the effects of adrenomedullin (AM) on dorsal root ganglion (DRG) and spinal motor (SM) neurons in rats. AM is a peptide highly expressed in the spinal cord. The study looks at how AM affects certain signaling pathways and the expression of neurotrophic factors. The researchers isolated and cultured DRG and SM neurons from rat embryos. They then used various methods to assess the expression of AM and its receptors, as well as the levels of cAMP, p-CREB, p-AKT, p-GSK-3β, BDNF, and NT-3 after AM treatment. The findings suggest that both DRG and SM neurons are targets of AM in the spinal cord. AM increases BDNF expression, which may have a beneficial role in protecting and regenerating sensory and motor neurons.

Study Duration

Not specified

Participants

120 Female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
AM increases cAMP accumulation and p-CREB levels in both DRG and SM neurons. This suggests a role for the cAMP/CREB signaling pathway in AM's effects.
2
AM increases p-AKT and p-GSK-3β in DRG neurons, but not in SM neurons, indicating different signaling mechanisms in these two types of neurons.
3
AM significantly increases BDNF expression in both DRG and SM neurons, and also increases NT-3 levels, particularly in SM neurons.

Research Summary

The study examined the expression of adrenomedullin (AM) and its receptors in rat dorsal root ganglion (DRG) and spinal motor (SM) neurons, finding that both neuron types express AM, CLR, RAMP2, and RAMP3. AM increased cAMP accumulation and p-CREB levels in both DRG and SM neurons, and increased p-AKT and p-GSK-3β in DRG neurons but not SM neurons. AM significantly increased BDNF expression in both DRG and SM neurons. These findings suggest that AM may have a beneficial role in protecting, supporting the survival, and promoting the regeneration of sensory and motor neurons in the spinal cord.

Practical Implications

Therapeutic Potential

AM could potentially be used as a therapeutic agent to protect and regenerate sensory and motor neurons in conditions such as spinal cord injuries or neurodegenerative diseases.

Targeted Therapies

The differing effects of AM on AKT/GSK-3β pathways in DRG versus SM neurons suggest the possibility of developing targeted therapies that selectively modulate these pathways for specific neuronal populations.

Further Research

Further studies are needed to fully elucidate the mechanisms by which AM exerts its neuroprotective and regenerative effects, particularly the role of BDNF and NT-3 in these processes.

Study Limitations

1
The study was performed on rat embryonic neurons, and the results may not be directly applicable to adult humans.
2
The exact underlying mechanisms by which AM increases BDNF and NT-3 expression were not fully elucidated.
3
The study did not investigate the long-term effects of AM on neuronal survival and regeneration.

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