Abstracts

Rationale: Nerve growth factor (NGF), neurotrophine-3 (NT3) and brain-derived neurotrophic factor (BDNF) are neurotrophins (NTs) involved in neuronal survival and plasticity of neurons in the central nervous system (CNS). Neuron losses in specific brain regions and altered NTs-expression have been described in epilepsy, depression and schizophrenia. In temporal lobe epilepsy (TLE), aberrant sprouting at fascia dentate is a hallmark. In schizophrenia, decreased neuronal spine density in multiple brain regions, including the cerebral cortex and the limbic system is commonly seen. These observations suggest that the mechanisms implicated in the development of these disorders might be associated with an overexpression or deficit in the synthesis or release of neurotrophins. We investigated the immunohistochemical expression of these 3 proteins in hippocampi of mesial temporal lobe epilepsy patients with no psychiatric comorbidities (TLE, n=16) and with interictal psychosis (TLE+P, n=13) or major depression (TLE+D, n=14). Methods: Hippocampi (n=43) were surgically obtained from medically intractable TLE patients and compared to autopsy controls (n=10) with no pre-mortem neurological disorders. Specimens were equally treated and submitted to hematoxilin-eosin and imunohistochemistry for NGF, NT3 and BDNF. Hippocampal regions examined were granular layer, hilar region, CA4, CA3, CA2, CA1, prosubiculum, subiculum, parasubiculum and entorhinal cortex. Positive immunoreactive area was estimated using an image analysis system software (ImageJ). Statistical analyses were performed using SPSS 11 and difference established when p<0.05. Results: NGF immunoreactivity (IR) at granular layer was higher in TLE group (mean: 3501,205 µm2) than in TLE+P (1605,030 µm2; ANOVA, p=0.006) and autopsy control group (1311,202 µm2; ANOVA, p=0.03). TLE+D group also exhibited higher NGF-IR in the granular layer (4794,535 µm2) than TLE+P (1605,030 µm2; ANOVA, p<0.001) and necropsy group (1311,202 µm2; ANOVA, p<0.001). Similarly, NGF-IR in TLE group was higher than the other groups in the CA2 region, and higher than TLE+P in the CA1 region, prosubiculum, subiculum and parasubiculum. NT3-IR was not different among groups except in the granular layer, where TLE group had higher IR (335,495 µm2) than the necropsy group (99,570 µm2; ANOVA, p=0.04). BDNF-IR was not different among groups except in the prosubiculum, where TLE+P group had higher IR (503,152 µm2) than TLE group (170,927 µm2; ANOVA, p=0.02). Conclusions: Neurotrophins are known to play a crucial role in neuronal growth and plasticity. We found differential expression of NGF among epileptic patients with and without psychiatric comorbidities. These findings suggest that decreased NGF expression, especially in the granular layer, in TLE+psychosis may underlie comorbid manifestation of psychiatric symptoms.