Abstract
In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.
Highlights
Zinc (Zn2+) is an important modulator of glutamatergic transmission in the central nervous system (CNS) [1], [2], [3]
We found an increased metallothioneins I/II (MT-I/II) expression in all hippocampal subfields of mesial temporal lobe epilepsy (MTLE) patients and in the fascia dentata of patients with temporal lobe epilepsy (TLE)-TD
In MTLE patients, MT-I/II expression correlated with astroglial population but not with neuronal population
Summary
Zinc (Zn2+) is an important modulator of glutamatergic transmission in the central nervous system (CNS) [1], [2], [3]. Studies in hippocampi from TLE patients who underwent epilepsy surgery have shown neuronal loss [18], [19], [20], increased glial reaction [21], [22], [23], [24] and reorganization of mossy fibers axon collaterals into the inner molecular layer of the granule cell dendrites [25], [19]. This synaptic reorganization of Zn2+-enriched terminals has been hypothesized to contribute to synchronous firing and epileptiform activity [19]. Besides the vesicular Zn2+, other intracellular Zn2+ pools are present in neurons [26], [27], which can contribute to neuronal death after an insult [28], [29], [27]
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