Introduction
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social communication and behavior. The causes of ASD are not fully understood, but some studies suggest that oxidative stress and inflammation in the brain may play a role. Oxidative stress is an imbalance between the production and removal of reactive oxygen species (ROS), which can damage cells and tissues. Inflammation is a response of the immune system to injury or infection, which can also cause tissue damage and impair brain function.
One potential way to prevent or treat ASD is to use substances that can reduce oxidative stress and inflammation in the brain. Agmatine is a natural compound that is produced from the amino acid arginine. Agmatine has been shown to have neuroprotective, anti-inflammatory, and antioxidant effects in various animal models of neurological disorders. However, the effects of agmatine on ASD have not been well studied.
A recent paper published in the Iranian Journal of Basic Medical Sciences1 investigated the effects of agmatine consumption during pregnancy on the development of ASD-like behaviors in rat offspring. The authors also measured the levels of oxidative stress markers and histopathological changes in the brain tissue of the rats.
Methods
The authors used a well-established rat model of ASD, in which pregnant rats are injected with valproic acid (VPA) on the 12th day of gestation. VPA is an anticonvulsant drug that can induce ASD-like behaviors and brain abnormalities in the offspring. The authors divided the pregnant rats into four groups: control, VPA, agmatine, and VPA + agmatine. The control group received saline injections, the VPA group received VPA injections, the agmatine group received agmatine injections, and the VPA + agmatine group received both VPA and agmatine injections. The doses of VPA and agmatine were 600 mg/kg and 40 mg/kg, respectively. The injections were given intraperitoneally (into the abdominal cavity).
The offspring were born and weaned normally, and then subjected to various behavioral tests at 8 weeks of age. The tests included the open field test, the social interaction test, the three-chamber test, and the marble burying test. These tests are commonly used to assess ASD-like behaviors in rodents, such as locomotor activity, anxiety, social preference, social novelty, and repetitive behavior.
The authors also collected brain tissue samples from the offspring and measured the levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in the hippocampus and cerebellum. MDA is a marker of lipid peroxidation, which is a type of oxidative damage to cell membranes. GSH and SOD are antioxidants that can scavenge ROS and protect cells from oxidative stress. The authors also performed histopathological examinations of the brain tissue samples, looking for signs of neuronal degeneration, inflammation, and apoptosis (cell death).
Results
The authors found that VPA injection during pregnancy induced ASD-like behaviors in the offspring, as evidenced by reduced locomotor activity, increased anxiety, decreased social preference and social novelty, and increased repetitive behavior. Agmatine injection during pregnancy attenuated these behavioral abnormalities, especially in the VPA + agmatine group. The authors also found that VPA injection during pregnancy increased the levels of MDA and decreased the levels of GSH and SOD in the hippocampus and cerebellum of the offspring, indicating increased oxidative stress and reduced antioxidant defense. Agmatine injection during pregnancy reversed these biochemical changes, restoring the balance between ROS production and removal. Furthermore, the authors found that VPA injection during pregnancy caused histopathological changes in the brain tissue of the offspring, such as neuronal loss, inflammation, and apoptosis. Agmatine injection during pregnancy prevented these changes, preserving the integrity and function of the brain tissue.
Conclusion
The authors concluded that agmatine consumption during pregnancy can reduce ASD-like behaviors and brain damage in rat offspring exposed to VPA. They suggested that agmatine may exert its beneficial effects by modulating oxidative stress and inflammation in the brain. They also proposed that agmatine may be a potential therapeutic agent for ASD, but further studies are needed to confirm its safety and efficacy in humans.
FAQ
How does valproic acid induce ASD-like behaviors and brain damage in rat offspring?
Valproic acid (VPA) is an anticonvulsant drug that can also cause birth defects and neurodevelopmental disorders in humans. VPA can cross the placenta and affect the fetal brain development by interfering with various molecular pathways, such as epigenetic regulation, neurogenesis, synaptogenesis, neurotransmission, and neuroinflammation. VPA can also increase the production of reactive oxygen species (ROS) and reduce the antioxidant defense in the brain, leading to oxidative stress and tissue damage. These effects can result in behavioral and brain abnormalities in the offspring that resemble ASD symptoms, such as impaired social interaction, communication, and learning.
How does agmatine reduce oxidative stress and inflammation in the brain?
Agmatine is a natural compound that can modulate various receptors and enzymes involved in the regulation of ROS production and removal. Agmatine can also inhibit the activation of inflammatory cells and cytokines that can cause brain damage and impair neuronal function. Agmatine can also enhance the expression of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione (GSH), that can scavenge ROS and protect cells from oxidative stress. By reducing oxidative stress and inflammation in the brain, agmatine can prevent or reverse the behavioral and brain abnormalities induced by VPA.
What are the advantages and disadvantages of using agmatine as a potential therapeutic agent for ASD?
The advantages of using agmatine as a potential therapeutic agent for ASD are:
- Agmatine is a natural compound that is endogenously produced in the body and has a low toxicity profile.
- Agmatine has multiple mechanisms of action that can target different aspects of ASD pathophysiology, such as oxidative stress, inflammation, neurotransmission, and neuroplasticity.
- Agmatine can be administered orally or intraperitoneally, which can facilitate its delivery and absorption in the body.
The disadvantages of using agmatine as a potential therapeutic agent for ASD are:
- Agmatine has not been tested in human clinical trials for ASD, so its safety and efficacy in humans are unknown.
- Agmatine may have interactions with other drugs or substances that can affect its pharmacokinetics and pharmacodynamics, such as antidepressants, opioids, alcohol, and nicotine.
- Agmatine may have side effects or adverse reactions in some individuals, such as hypotension, nausea, vomiting, diarrhea, and headache.
Source:
https://ijbms.mums.ac.ir/article_23307_2ffdf3ade1dac6b1c007ad73ab399179.pdf