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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

Correlative light and electron microscopy of the CA1 region from a sclerotic hippocampus. (A) Photomicrograph of a 2-μm-thick semithin plastic section stained with 1% toluidine blue to show the numerous astrocytes and very few neurons. (B) Low-power electron micrograph taken after sectioning the semithin preparation of the boxed area in (A) showing the same group of astrocytes. (C) Electron micrograph illustrating the adjacent neuropil with abundant glial processes (some of them indicated with asterisks) and a synapse (arrow). (D) Higher magnification of the asymmetric synapse indicated with an arrow in (C). Note that the presynaptic element is filled with degenerating structures and a prominent postsynaptic density is evident (arrowheads). (E) Electron micrograph of an isolated neuron (n) and its adjacent neuropil. (F) Higher magnification of the boxed area in (E) to indicate the presence of glial processes (asterisk) around the neuronal cell body (n). Scale bar [in (F)]: 70 μm in (A), 11 μm in (B), 2.8 μm in (C), 0.5 μm in (D), 5.6 μm in (E), and 1 μm in (F).
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Figure 6: Correlative light and electron microscopy of the CA1 region from a sclerotic hippocampus. (A) Photomicrograph of a 2-μm-thick semithin plastic section stained with 1% toluidine blue to show the numerous astrocytes and very few neurons. (B) Low-power electron micrograph taken after sectioning the semithin preparation of the boxed area in (A) showing the same group of astrocytes. (C) Electron micrograph illustrating the adjacent neuropil with abundant glial processes (some of them indicated with asterisks) and a synapse (arrow). (D) Higher magnification of the asymmetric synapse indicated with an arrow in (C). Note that the presynaptic element is filled with degenerating structures and a prominent postsynaptic density is evident (arrowheads). (E) Electron micrograph of an isolated neuron (n) and its adjacent neuropil. (F) Higher magnification of the boxed area in (E) to indicate the presence of glial processes (asterisk) around the neuronal cell body (n). Scale bar [in (F)]: 70 μm in (A), 11 μm in (B), 2.8 μm in (C), 0.5 μm in (D), 5.6 μm in (E), and 1 μm in (F).

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)

Correlative light and electron microscopy of the CA1 region from a sclerotic hippocampus. (A) Photomicrograph of a 2-μm-thick semithin plastic section stained with 1% toluidine blue to show the numerous astrocytes and very few neurons. (B) Low-power electron micrograph taken after sectioning the semithin preparation of the boxed area in (A) showing the same group of astrocytes. (C) Electron micrograph illustrating the adjacent neuropil with abundant glial processes (some of them indicated with asterisks) and a synapse (arrow). (D) Higher magnification of the asymmetric synapse indicated with an arrow in (C). Note that the presynaptic element is filled with degenerating structures and a prominent postsynaptic density is evident (arrowheads). (E) Electron micrograph of an isolated neuron (n) and its adjacent neuropil. (F) Higher magnification of the boxed area in (E) to indicate the presence of glial processes (asterisk) around the neuronal cell body (n). Scale bar [in (F)]: 70 μm in (A), 11 μm in (B), 2.8 μm in (C), 0.5 μm in (D), 5.6 μm in (E), and 1 μm in (F).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Correlative light and electron microscopy of the CA1 region from a sclerotic hippocampus. (A) Photomicrograph of a 2-μm-thick semithin plastic section stained with 1% toluidine blue to show the numerous astrocytes and very few neurons. (B) Low-power electron micrograph taken after sectioning the semithin preparation of the boxed area in (A) showing the same group of astrocytes. (C) Electron micrograph illustrating the adjacent neuropil with abundant glial processes (some of them indicated with asterisks) and a synapse (arrow). (D) Higher magnification of the asymmetric synapse indicated with an arrow in (C). Note that the presynaptic element is filled with degenerating structures and a prominent postsynaptic density is evident (arrowheads). (E) Electron micrograph of an isolated neuron (n) and its adjacent neuropil. (F) Higher magnification of the boxed area in (E) to indicate the presence of glial processes (asterisk) around the neuronal cell body (n). Scale bar [in (F)]: 70 μm in (A), 11 μm in (B), 2.8 μm in (C), 0.5 μm in (D), 5.6 μm in (E), and 1 μm in (F).
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