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A stereological study of synapse number in the epileptic human hippocampus.

Alonso-Nanclares L, Kastanauskaite A, Rodriguez JR, Gonzalez-Soriano J, Defelipe J - Front Neuroanat (2011)

Bottom Line: Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients.We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher.Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Functional and Systems Neurobiology, Instituto Cajal (Consejo Superior de Investigaciones Cientificas) Madrid, Spain.

ABSTRACT
Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

No MeSH data available.


Related in: MedlinePlus

Electron microscopy to illustrate the morphology of the synapses in the sclerotic CA1. (A) Normal symmetric synapse showing a typical thin postsynaptic density (double arrow). An asymmetric synapse (single arrow) displaying a characteristic thick postsynaptic density is found on the same postsynaptic element. (B) Electron micrograph illustrating axon terminals (t) forming synapses with different appearance. The arrow indicates an asymmetric synapse established by a normal-looking axon terminal. The arrowhead points to an asymmetric synapse whose presynaptic axon terminal has an abnormal appearance and in which virtually all synaptic vesicles are close to the synaptic junction. In (A) and (B), some processes of reactive glia are indicated by asterisks. t, axon terminal. Scale bar [in (B)]: 0.5 μm in (A) and 0.4 μm in (B).
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Figure 7: Electron microscopy to illustrate the morphology of the synapses in the sclerotic CA1. (A) Normal symmetric synapse showing a typical thin postsynaptic density (double arrow). An asymmetric synapse (single arrow) displaying a characteristic thick postsynaptic density is found on the same postsynaptic element. (B) Electron micrograph illustrating axon terminals (t) forming synapses with different appearance. The arrow indicates an asymmetric synapse established by a normal-looking axon terminal. The arrowhead points to an asymmetric synapse whose presynaptic axon terminal has an abnormal appearance and in which virtually all synaptic vesicles are close to the synaptic junction. In (A) and (B), some processes of reactive glia are indicated by asterisks. t, axon terminal. Scale bar [in (B)]: 0.5 μm in (A) and 0.4 μm in (B).

Mentions: In the sclerotic CA1, numerous glial processes were widespread and the relatively few surviving pyramidal neurons were surrounded by glial processes (Figures 6 and 7). Very few synapses were observed and moreover, these sparse synapses displayed a variety of morphological alterations. These alterations mostly consisted of the presence of organelles that appeared to be degenerating in the presynaptic elements (Figure 6D), as well as a decrease or virtual lack of synaptic vesicles (Figure 7B). Although we did not observe alterations to the postsynaptic elements, we cannot discard that subtle changes passed unnoticed.


A stereological study of synapse number in the epileptic human hippocampus.

Alonso-Nanclares L, Kastanauskaite A, Rodriguez JR, Gonzalez-Soriano J, Defelipe J - Front Neuroanat (2011)

Electron microscopy to illustrate the morphology of the synapses in the sclerotic CA1. (A) Normal symmetric synapse showing a typical thin postsynaptic density (double arrow). An asymmetric synapse (single arrow) displaying a characteristic thick postsynaptic density is found on the same postsynaptic element. (B) Electron micrograph illustrating axon terminals (t) forming synapses with different appearance. The arrow indicates an asymmetric synapse established by a normal-looking axon terminal. The arrowhead points to an asymmetric synapse whose presynaptic axon terminal has an abnormal appearance and in which virtually all synaptic vesicles are close to the synaptic junction. In (A) and (B), some processes of reactive glia are indicated by asterisks. t, axon terminal. Scale bar [in (B)]: 0.5 μm in (A) and 0.4 μm in (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3046382&req=5

Figure 7: Electron microscopy to illustrate the morphology of the synapses in the sclerotic CA1. (A) Normal symmetric synapse showing a typical thin postsynaptic density (double arrow). An asymmetric synapse (single arrow) displaying a characteristic thick postsynaptic density is found on the same postsynaptic element. (B) Electron micrograph illustrating axon terminals (t) forming synapses with different appearance. The arrow indicates an asymmetric synapse established by a normal-looking axon terminal. The arrowhead points to an asymmetric synapse whose presynaptic axon terminal has an abnormal appearance and in which virtually all synaptic vesicles are close to the synaptic junction. In (A) and (B), some processes of reactive glia are indicated by asterisks. t, axon terminal. Scale bar [in (B)]: 0.5 μm in (A) and 0.4 μm in (B).
Mentions: In the sclerotic CA1, numerous glial processes were widespread and the relatively few surviving pyramidal neurons were surrounded by glial processes (Figures 6 and 7). Very few synapses were observed and moreover, these sparse synapses displayed a variety of morphological alterations. These alterations mostly consisted of the presence of organelles that appeared to be degenerating in the presynaptic elements (Figure 6D), as well as a decrease or virtual lack of synaptic vesicles (Figure 7B). Although we did not observe alterations to the postsynaptic elements, we cannot discard that subtle changes passed unnoticed.

Bottom Line: Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients.We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher.Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Functional and Systems Neurobiology, Instituto Cajal (Consejo Superior de Investigaciones Cientificas) Madrid, Spain.

ABSTRACT
Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

No MeSH data available.


Related in: MedlinePlus