From the Guidelines
Besides fluoxetine, metformin has been shown to promote neurogenesis, neuroplasticity, and angiogenesis, 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 recent evidence from a 2023 study published in the BMJ, which suggests that metformin may promote neurogenesis by activating a protein kinase CPB transcriptional coactivator pathway involved with the typical genesis of neurons from neural progenitor cells 1.
Key Findings
- Metformin, an anti-hyperglycemic first line therapy for type 2 diabetes mellitus, has been identified as a potential neurogenesis targeted treatment 1.
- Other potential treatments under investigation include antioxidant N-acetylcysteine, ginkgo biloba, mesna, ganglioside-monosialic acid, and transdermal nicotine, which target neuronal protection, differentiation, and neurogenesis 1.
- Non-pharmaceutical approaches such as brain training, physical brain stimulation using techniques such as transcranial magnetic stimulation, and exercise are also being investigated as potential therapeutic avenues for enhancing neuroplasticity and cognitive function 1.
Mechanisms of Action
- Metformin's ability to promote neurogenesis is thought to be mediated by the activation of a protein kinase CPB transcriptional coactivator pathway involved with the typical genesis of neurons from neural progenitor cells 1.
- Other treatments under investigation may work through various mechanisms including increasing neurotrophic factors like BDNF and NGF, reducing inflammation, promoting angiogenesis, enhancing mitochondrial function, and facilitating the formation of new synapses 1.
Clinical Implications
- Metformin may be a useful adjunctive treatment for patients with cognitive impairment, particularly those with a history of cancer treatment.
- Further research is needed to fully elucidate the effects of metformin and other potential treatments on neuroplasticity, neurogenesis, and cognitive function in humans.
From the Research
Neuroplasticity, Neurogenesis, and Angiogenesis
- Besides Fluoxetine, physical exercise has been shown to promote neuroplasticity, neurogenesis, and angiogenesis, enhancing spatial and non-spatial memory systems, and influencing cortical excitability, with anti-oxidative stress, anti-inflammatory, and anti-apoptotic effects 2.
- Running has been found to correlate with an increase of hippocampal neurogenesis and plasticity, although the gene pathways involved are only partially coincident with those of fluoxetine 2.
Mechanisms of Action
- Fluoxetine has been shown to exert its therapeutic effects, at least in part, by promoting neuroplasticity through increased brain-derived neurotrophic factor (BDNF)/tropomyosin-related receptor kinase B (TrkB) signalling 3.
- The neuroplastic effects of fluoxetine are not solely mediated by the inhibition of the serotonin transporter (5-HTT), but might rely, at least in part, on 5-HTT-independent direct activation of TrkB 3.
- Fluoxetine has been found to attenuate stress-induced depressive-like behavior through modulation of hippocampal GAP43 and neurogenesis in male rats 4.
Neuroprotective Effects
- Fluoxetine has been shown to have neuroprotective effects, including decreased neuronal loss and inflammation, improved survival and functional recovery, enhanced neurogenesis, and prevented an early pathological increase in neural stem cell recruitment in the subgranular zone (SGZ) of the hippocampus 5.
- Fluoxetine has been found to promote neurogenesis or angiogenesis in the dentate gurus (DG), and enhance axonal and dendritic reorganization 6.
Behavioral Effects
- Fluoxetine has been found to alleviate the symptoms of post-stroke depression (PSD), and help motor recovery in stroke patients 6.
- Chronic administration of fluoxetine has been shown to induce increased excitability of mature granule cells (GCs), and promote behavioral recovery after stroke in animal experiments 6.