Loss and sprouting of nitric oxide synthase neurons in the human epileptic hippocampus.
OBJECTIVE
Nitric oxide (NO) has been implicated in a variety of functions, including the control of synaptic plasticity and sensory signaling. Current evidence suggests that this unconventional neurotransmitter mediates N-methyl-d-aspartate (NMDA) receptor-linked excitotoxicity. This study describes the expression of neuronal NO synthase (nNOS) immunoreactivity (IR) in hippocampi from patients with temporal lobe epilepsy (TLE).


METHODS
Hippocampi from patients with clinical symptoms, neuroimaging, and EEG typical of hippocampal sclerosis (HS; n = 22) were compared with those from patients with neocortical temporal lesions (NONHS; n = 4) and autopsy (AUT; n = 18) patients for total cells, and nNOS-IR neuron and puncta densities.


RESULTS
Compared with AUT, HS hippocampi had significantly less nNOS-IR neuron densities in the fascia dentata (FD); hilus, and CA4, CA3, CA2, and CA1 subfields. HS hippocampi had significantly greater nNOS-IR puncta densities in the FD, as compared with AUT and NONHS.


CONCLUSIONS
Our results show that hippocampi from TLE patients exhibit a loss of nNOS-IR neurons and an abnormal FD innervation. The release of NO can influence the dynamics of ionic channels and neurotransmitter release, thus affecting neuronal membrane potential. Because the NOergic transmission does not obey the topographic constraints imposed on conventional transmitters, target cells can be stimulated even in regions with severe deafferentation. The plastic changes described here may contribute to abnormal hippocampal excitability.
Leite
J P
JP
Department of Neurology, University Campus, University of Sao Paulo School of Medicine at Ribeirão Preto, CEP 14049-900, Brazil. jpleite@fmrp.usp.br
Chimelli
L
L
Terra-Bustamante
V C
VC
Costa
E T
ET
Assirati
J A
JA
de Nucci
G
G
Martins
A R
AR
D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009411:Nerve Endings / Q000503:physiopathology; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D012598:Sclerosis
C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I