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 neurogenesis targeted treatments 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 involved with the typical genesis of neurons from neural progenitor cells 1. Additionally, acupuncture has been shown to promote neurogenesis and improve synaptic plasticity in the hippocampus, with potential mechanisms including the regulation of 5-HT receptor levels and the GluN2B/CaMKII/CREB signaling pathway 1. However, fluoxetine remains the most well-studied and widely used treatment for promoting neuroplasticity.
Clinical Implications
The use of fluoxetine to promote neuroplasticity has significant clinical implications, particularly in the treatment of cognitive impairment and depression. Fluoxetine should be considered as a potential treatment option for patients with cognitive impairment or depression, particularly those who have not responded to other treatments. Further research is needed to fully understand the mechanisms by which fluoxetine promotes neuroplasticity and to explore its potential use in other clinical contexts.
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