Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome.

Ludmyla Kandratavicius,Carlos Gilberto Carlotti,Joao Pereira Leite,Jaime Eduardo Hallak,Joao Alberto Assirati

doi:10.1186/s40478-014-0081-2

Abstract

Epilepsy and psychiatric comorbidities are frequently associated, but their common biological substrate is unknown. We have previously reported altered structural elements and neurotrophins (NTs) expression in mesial temporal lobe epilepsy (MTLE) patients with psychiatric comorbidities. NTs receptors can regulate neurotransmission and promote neuroplasticity, being important candidates in the regulation and manifestation of psychopatological states and seizure-related events. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, MTLE + interictal psychosis derived from epilepsy surgery, and control necropsies were investigated for p75NTR, TrkB, TrkA, and TrkC immunohistochemistry. Increased expression of p75NTR, decreased TrkA, unaltered TrkC, and complex alterations involving TrkB expression were seen in MTLE groups. Increased TrkB expression in patients without complete seizure remission and in those with secondarily generalized seizures was seen. Decreased p75NTR expression associated with interictal psychosis, and increased TrkB in those with psychosis or major depression was also reported, although their p75NTR/TrkB ratios were lower than in MTLE without psychiatric comorbidities. Our results provide evidence of alterations in expression of NTs receptors in the epileptogenic hippocampus that are differentially modulated in presence of psychiatric comorbidities. As already explored in animal models, even in chronic human MTLE increased TrkB expression, among other NT receptors alterations, may play a major role in seizure type, frequency and surgery outcome.

Highlights

Psychiatric comorbidities are frequent in epileptic patients, the precise nature of this association is still matter of debate [1,2]
Two patients in Mesial temporal lobe epilepsy (MTLE) group, one patient in MTLE + D, and four patients in MTLE + P group presented with auras and seizures post-surgery, frequency was decreased if compared with pre-surgery period
The remaining of patients without complete remission had only auras, and the proportion of patients with this outcome was higher in the group with history of major depression when compared to MTLE without psychiatric comorbidities (Fisher’s Exact Test, p = 0.046)

Summary

Introduction

Psychiatric comorbidities are frequent in epileptic patients, the precise nature of this association is still matter of debate [1,2]. We have recently shown neuropathological data suggesting that there is a Hippocampal NTs are upregulated in MTLE patients [9,10] and in animal models of epilepsy [11,12,13,14,15,16]. In human MTLE, a qualitative study performed in the dentate gyrus and Ammon’s horn showed increased p75NTR expression in glia and remaining neurons, and few alterations in Trk expression [20]. In animal models of epilepsy, increased NT receptors expression has been related to increased excitability [21,22,23,24,25]

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Discussion

Conclusion