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Neurotrophins in mesial temporal lobe epilepsy with and without psychiatric comorbidities

Ludmyla Kandratavicius1, Mariana Raquel Monteiro, Joao Alberto Assirati

  • 1From the Department of Neurosciences and Behavior, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil (LK, MRM, JEH, JPL); Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil (LK, JEH, JPL); National Institute of Science and Technology in Translational Medicine (INCT-TM-CNPq), Brazil (JEH); Department of Surgery, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil (JAA Jr., CGC Jr.).

Journal of Neuropathology and Experimental Neurology
|October 17, 2013
PubMed

Insights

Mossy fiber sprouting in epilepsy is linked to neurotrophin expression in the hippocampus. These findings suggest distinct brain changes may underlie psychiatric issues in epilepsy patients.

Area of Science:

  • Neuroscience
  • Neuropathology
  • Epileptology

Background:

  • Epilepsy and psychiatric disorders frequently co-occur, but clinicopathologic links are poorly understood.
  • Previous research identified differential mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (MTLE) patients with psychosis (MTLE + P) or major depression (MTLE + D).
  • Neurotrophins (NTs) are implicated in promoting MFS, suggesting a role in epilepsy-related brain changes.

Purpose of the Study:

  • To investigate the relationship between MFS, neuronal density, and neurotrophin (NGF, BDNF, NT3) immunoreactivity in the hippocampi of MTLE patients with and without psychiatric comorbidities.
  • To explore correlations between these factors and seizure characteristics, neuropsychological scores, and psychiatric medication use.

Main Methods:

  • Analysis of hippocampal tissue from MTLE patients (with and without psychiatric history), and control necropsies.
  • Assessment of mossy fiber sprouting (MFS), neuronal density, and immunoreactivity for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT3).
  • Correlation analysis with seizure frequency, seizure type, neuropsychological scores, and psychiatric medication (fluoxetine, haloperidol).

Main Results:

  • MFS correlated with hippocampal NGF immunoreactivity and seizure frequency.
  • Patients with secondarily generalized seizures had less NGF immunoreactivity than those with complex partial seizures.
  • Increased NT immunoreactivity was observed in MTLE patients compared to controls, but it was lower in MTLE + P patients, correlating with neuropsychological scores.
  • Fluoxetine use in MTLE + D patients was associated with higher BDNF immunoreactivity.
  • Haloperidol use in MTLE + P patients correlated with decreased neuronal density and NGF/BDNF immunoreactivity in specific hippocampal subfields.
  • No significant differences in NT3 immunoreactivity were found among groups.

Conclusions:

  • A strong association exists between MFS and neurotrophin expression in the hippocampi of MTLE patients.
  • Distinct structural and neurochemical differences in the hippocampus may contribute to the development or persistence of psychiatric comorbidities in MTLE.
  • These findings highlight potential therapeutic targets for managing psychiatric aspects of epilepsy.

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