Neurotrophic Factors in Epileptogenesis and Seizure Modulation

Neurotrophic factors are secreted proteins that govern neuronal survival, differentiation and synaptic plasticity. In the context of epilepsy, they exert complex influences on network excitability and structural remodelling. Brain-derived neurotrophic factor (BDNF) is the most extensively studied, with evidence for both pro-epileptogenic actions—through promotion of aberrant synaptic sprouting and enhanced excitatory transmission—and anti-epileptogenic effects via neuroprotection and support of inhibitory circuitry. Other members of the family, such as glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor-2 (FGF-2) and ciliary neurotrophic factor (CNTF), modulate excitatory/inhibitory balance, neuroinflammation and neuronal network stability. Dysregulation of tropomyosin receptor kinase B (TrkB) signalling and downstream cascades—including ERK and PI3K/AKT—has been implicated in maladaptive plasticity. Understanding how neurotrophic factors influence epileptogenesis offers routes to biomarker discovery and novel therapeutic strategies aimed at restoring physiological network function.

Research from Nature Portfolio

Deletion of Phospholipase Cγ1 in GABAergic Neurons Increases Seizure Susceptibility in Aged Mice – Targeted ablation of PLCγ1 in inhibitory interneurons leads to a reduction in GABAergic synaptic density within hippocampal subregions, disrupting excitatory/inhibitory balance and precipitating handling-induced seizures. The study highlights a critical role for PLCγ1 in maintaining inhibitory synapse integrity and suggests that modulation of this enzyme may intersect with TrkB-dependent neurotrophic signalling.

Neurotrophic Factors in Epileptogenesis and Seizure Modulation publication trend

The graph below shows the total number of articles in neurotrophic factors in epileptogenesis and seizure modulation across all publications each year (not limited to Nature Index journals).

Technical terms

Neurotrophic factor: A protein that supports neuronal growth, survival and synaptic function.

Epileptogenesis: The process by which a normal brain develops the predisposition to generate spontaneous seizures.

Seizure modulation: The alteration of neuronal excitability or network synchrony to change seizure threshold or frequency.

Brain-derived neurotrophic factor (BDNF): A key neurotrophin that binds TrkB to regulate synaptic plasticity and neuronal resilience.

Glial cell line-derived neurotrophic factor (GDNF): A factor that promotes neuronal survival and influences network excitability, with emerging biomarker potential.

Tropomyosin receptor kinase B (TrkB): The high-affinity receptor for BDNF, activating intracellular cascades such as ERK and PI3K/AKT.

Excitatory/inhibitory balance (E/I balance): The equilibrium between excitatory and inhibitory synaptic inputs critical for stable neural circuit function.

References

1. Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice. Neurobiology of Disease (2024).
2. Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate. International Journal of Molecular Sciences (2023).
3. The Possible Role of Brain-derived Neurotrophic Factor in Epilepsy. Neurochemical Research (2023).
4. Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice. Scientific Reports (2019).