Altered synaptic circuitry in the human temporal neocortex removed from epileptic patients

Marco, Pilar; DeFelipe, Javier

doi:10.1007/pl00005608

Cited by 78 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, those data conflict with other findings that failed to show a difference in overall neuronal density between TLE and control neocortex (Babb et al, 1984). Most of those investigations based their conclusions either on qualitative evaluations (DeFelipe et al, 1993;Ferrer et al, 1994, Marco et al, 1996Spreafico et al, 1998) or semiquantitative measurements (Babb et al, 1984;Sisodiya et al, 1995;Emery et al, 1997;Marco and DeFelipe, 1997;Mitchell et al, 1999) that estimated cells in the two-dimensional plane. In studies of cortical abnormalities in other diseases, a methodological advance, i.e., design-based stereology, allows cells to be counted using three-dimensional probes and has proved highly successful in establishing whether neurons are lost (Everall et al…”

contrasting

confidence: 48%

“…Our results suggest that the reduction in volume is independent of a change in neuronal number. Qualitative assessments of neocortical tissue in TLE cases have uncovered small regions depleted of parvalbumin immunoreactivity and reduced in synapses (DeFelipe et al, 1993;Marco and DeFelipe, 1997;Spreafico et al, 1998;DeFelipe, 1999). Although such analyses provide important explanations for the pathology accompanying seizures, they pro- Figure 7.…”

Section: No Neuronal Loss In Tle Neocortexmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal Hypertrophy in the Neocortex of Patients with Temporal Lobe Epilepsy

et al. 2001

View full text Add to dashboard Cite

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease. Key words: temporal lobe epilepsy; stereology; Brodmann's area 38; ectopia; cortical atrophy; neuronal hypertrophy; hippocampal sclerosisHippocampal sclerosis (HS) is the most frequently encountered pathologic abnormality in intractable epilepsy. There is however increasing evidence of more widespread temporal lobe pathology in HS patients (Nakasato et al., 1992;Sisodiya et al., 1995) and prevalent temporal lobe hypometabolism in patients with temporal lobe epilepsy (TLE) (Rausch et al., 1994). Moreover, magnetic resonance imaging (MRI) studies show a reduction in temporal lobe volume both ipsilateral and contralateral to the seizure focus (Lee et al., 1995Marsh et al., 1997). Volume reduction is also independent of the presence of HS (Sisodiya et al., 1997), which indicates that it underlies a broader spectrum than mesial temporal disease alone.Pathologic studies of TLE neocortex are dominated by those focused on readily detectable lesions and gross developmental abnormalities (Choi and Matthias, 1987;Haines et al., 1991;Raymond et al., 1995). There are far fewer investigations of subtle morphological abnormalities in the neocortex than in the hippocampus (Mathern et al., 1995), even though such studies might be expected to answer basic questions about epileptogenic activity originating outside the hippocampus and gross volume reductions in the temporal lobe.A common view of cortical pathology in TLE is that of neuronal loss. This notion is based on reports of reduced numbers of inhibitory neurons (DeFelip...

show abstract

contrasting

confidence: 48%

Section: No Neuronal Loss In Tle Neocortexmentioning

confidence: 99%

Neuronal Hypertrophy in the Neocortex of Patients with Temporal Lobe Epilepsy

et al. 2001

View full text Add to dashboard Cite

show abstract

“…A similar explanation probably applies to the decline in synaptophysin expression seen in other degenerative disorders (Ince et al, 1995;Samuel et al, 1997;Ferrer et al, 2000), following experimental lesions (e.g., Masliah et al, 1991;Gonzales-Dunia et al, 2000), with aging Eastwood et al, 1994), and with age-associated memory impairment (Smith et al, 2000). Equally, the localized increases of synaptic proteins seen in temporal lobe epilepsy (Honer et al, 1994;Looney et al, 1999;Proper et al, 2000) are associated with synaptic sprouting (Marco and DeFelipe, 1997), and this relationship likely exists during lesion-induced plasticity too (Boschert et al, 1996;Bergmann et al, 1997).…”

Section: What Do Altered Synaptic Protein Levels In Schizophrenia Mean?mentioning

confidence: 88%

Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia

Harrison¹,

Eastwood²

2001

Hippocampus

201

View full text Add to dashboard Cite

Cytoarchitectural changes in the hippocampal formation have been prominent among the various neuropathological abnormalities reported in schizophrenia. Replicated positive findings include decreased neuronal size and alterations in presynaptic and dendritic markers. These findings, in the absence of neurodegenerative changes, suggest that there are alterations in the neural circuitry in schizophrenia. These may represent the anatomical correlate of the aberrant functional connectivity described in neuroimaging studies, which in turn contributes to the psychotic and cognitive symptomatology of the disorder. The identity of the affected hippocampal circuits remains unclear; there is evidence for both glutamatergic and GABAergic involvement, and perhaps for a gradient of pathology in which changes are most apparent in CA4 and the subiculum, and least in CA1. The data, their interpretation, and their limitations are discussed, with particular emphasis upon molecular and immunological studies of synaptic protein gene expression.

show abstract

“…In most patients with mesial TLE, the temporal neocortex is nevertheless involved, as evidenced from PET studies, 42 morphologic analysis, 43 and pathologic findings. 44,45 Clear relationships between neuronal loss and seizures and between the sprouting phenomenon and neuronal loss have been shown to exist in several studies. [26][27][28][29][30][46][47][48] Sprouting and new synapse formation occur both in hippocampus and in neocortical layer V, and a relationship between sprouting and the amount of interictal spikes generated at these sites has been demonstrated in an experimental model.…”

Section: Methodsmentioning

confidence: 96%

Intractable temporal lobe epilepsy with rare spikes is less severe than with frequent spikes

Rosati¹,

Aghakhani²,

Bernasconi³

et al. 2003

Neurology

View full text Add to dashboard Cite

This study identified a subgroup of patients with nonlesional intractable TLE with no or few IEA. Oligospikers have a later age at seizure onset, less frequent and less severe seizures, besides a lower incidence of HA. The similarity of etiologic factors compared with patients with frequent IEA suggests that the rarity of spikes could reflect a disease not really distinct but less severe, even though still intractable and incapacitating enough to consider surgery. In spite of the absence or paucity of IEA, oligospikers have excellent surgical outcome.

show abstract

Altered synaptic circuitry in the human temporal neocortex removed from epileptic patients

Cited by 78 publications

References 40 publications

Neuronal Hypertrophy in the Neocortex of Patients with Temporal Lobe Epilepsy

Neuronal Hypertrophy in the Neocortex of Patients with Temporal Lobe Epilepsy

Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia

Intractable temporal lobe epilepsy with rare spikes is less severe than with frequent spikes

Contact Info

Product

Resources

About