What promotes neuroplasticity, neurogenesis, and the formation of new neural pathways, enhancing spatial and non-spatial memory systems, and influencing cortical excitability, with anti-oxidative stress, anti-inflammatory, and anti-apoptotic (programmed cell death) effects?

From the Guidelines

Fluoxetine, a commonly prescribed antidepressant, has been shown to promote neuroplasticity, neurogenesis, and the formation of new neural pathways, enhancing spatial and non-spatial memory systems, and influencing cortical excitability, with anti-oxidative stress, anti-inflammatory, and anti-apoptotic effects. This is based on the most recent and highest quality study available, which found that fluoxetine stimulates hippocampal neurogenesis, increases BDNF, and improves neuronal survival rates 1.

Key Mechanisms

The mechanisms by which fluoxetine promotes neuroplasticity include:

• Stimulation of hippocampal neurogenesis
• Increase in BDNF
• Improvements in neuronal survival rates
• Up-regulation of the phosphorylation of Ser9 of glycogen synthase kinase-3-β and increasing β-catenin in the nucleus
• Increase in proliferation of neural progenitor cells

Comparison to Other Treatments

Other potential treatments that have been investigated for their ability to promote neuroplasticity include:

• Metformin, an anti-hyperglycemic first line therapy for type 2 diabetes mellitus, which may promote neurogenesis by activating a protein kinase CPB transcriptional coactivator pathway 1
• Antioxidant N-acetylcysteine, which is undergoing testing for safety and tolerability in patients with ovarian cancer receiving platinum based chemotherapeutic agents 1
• Ginkgo biloba, which has shown potential clinical efficacy for Alzheimer’s disease and is being tested for antioxidative and anti-inflammatory properties 1
• Electroacupuncture, which has been shown to promote neurogenesis, improve synaptic plasticity, and alleviate depression-like behavior in animal models 1

Clinical Implications

The clinical implications of these findings are that fluoxetine may be a useful treatment for promoting neuroplasticity and improving cognitive function in patients with various neurological and psychiatric disorders. However, further clinical trials are needed to confirm the efficacy of fluoxetine in humans.

Limitations

The current evidence is based on animal studies and clinical trials are needed to confirm the findings in humans. Additionally, the exact mechanisms by which fluoxetine promotes neuroplasticity are not fully understood and require further investigation.

From the Research

Factors Promoting Neuroplasticity and Neurogenesis

• Physical exercise, particularly moderate to high intensity aerobic exercise, has been shown to induce neuroplasticity and increase the level of peripheral Brain Derived Neurotrophic Factor (BDNF) 2
• Omega-3 fatty acids, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have anti-oxidative stress, anti-inflammatory, and anti-apoptotic effects, and are involved in neurogenesis and neuroplasticity 3, 4
• A diet rich in antioxidants and omega-3 fatty acids may help prevent oxidative damage and promote cognitive health during aging 4, 5
• Cognitive engagement and mental activity have been shown to enhance brain and cognitive reserve, and promote neuroplasticity 5

Mechanisms Underlying Neuroplasticity and Neurogenesis

• Neurotrophic signaling, including the increase of BDNF, plays a key role in neuroplasticity and neurogenesis 2, 5
• Inflammation, stress response, and antioxidant defense are common substrates modulated by lifestyle factors, including physical activity and diet, to promote neuroplasticity 5
• Synaptic plasticity, including long-term potentiation, and modulation of synaptic protein expression, are involved in the effects of omega-3 fatty acids on neurogenesis and neuroplasticity 3

Therapeutic Implications

• Moderate to high intensity aerobic exercise may be a fundamental therapeutic strategy to include in interventions aiming to repair or delay neurological dysfunctions 2
• Omega-3 fatty acids and antioxidants may be useful in the prevention and treatment of neurodegenerative diseases, including Alzheimer's disease and stroke 3, 6, 4
• Lifestyle modifications, including physical activity, cognitive engagement, and diet, may be an effective strategy for promoting cognitive health during aging 5