Astrocyte Role in Temporal Lobe Epilepsy and Development of Mossy Fiber Sprouting

Epilepsy affects approximately 50 million people worldwide, with 60% of adult epilepsies presenting an onset of focal origin. The most common focal epilepsy is temporal lobe epilepsy (TLE). The role of astrocytes in the presentation and development of TLE has been increasingly studied and discussed within the literature. The most common histopathological diagnosis of TLE is hippocampal sclerosis. Hippocampal sclerosis is characterized by neuronal cell loss within the Cornu ammonis and reactive astrogliosis. In some cases, mossy fiber sprouting may be observed. Mossy fiber sprouting has been controversial in its contribution to epileptogenesis in TLE patients, and the mechanisms surrounding the phenomenon have yet to be elucidated. Several studies have reported that mossy fiber sprouting has an almost certain co-existence with reactive astrogliosis within the hippocampus under epileptic conditions. Astrocytes are known to play an important role in the survival and axonal outgrowth of central and peripheral nervous system neurons, pointing to a potential role of astrocytes in TLE and associated cellular alterations. Herein, we review the recent developments surrounding the role of astrocytes in the pathogenic process of TLE and mossy fiber sprouting, with a focus on proposed signaling pathways and cellular mechanisms, histological observations, and clinical correlations in human patients.

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Reduced mossy fiber sprouting in temporal lobe epilepsy with psychosis: The role of brain derived neurotrophic factor and TRKB

Schizophrenia Research ◽

10.1016/s0920-9964(03)80593-5 ◽

2003 ◽

Vol 60 (1) ◽

pp. 70

Author(s):

J.S. Dunham ◽

J.E. Hallak ◽

C. Toro ◽

R. Guarnieri ◽

A.W. Zuardi ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Neurotrophic Factor ◽

Mossy Fiber ◽

Brain Derived Neurotrophic Factor ◽

Mossy Fiber Sprouting

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Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms22083860 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3860

Author(s):

Elisa Ren ◽

Giulia Curia

Keyword(s):

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Knowledge ◽

Focal Epilepsy ◽

Ex Vivo ◽

Hippocampal Sclerosis ◽

Control Group ◽

Epileptogenic Zone ◽

Epileptiform Discharges

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

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Epilepsy and Ecstatic Experiences: The Role of the Insula

Brain Sciences ◽

10.3390/brainsci11111384 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1384

Author(s):

Fabienne Picard ◽

Peter Bossaerts ◽

Fabrice Bartolomei

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Mystical Experience ◽

Focal Epilepsy ◽

Anterior Insula ◽

External Signal ◽

Prediction Errors ◽

Rare Form ◽

The World

Ecstatic epilepsy is a rare form of focal epilepsy in which the aura (beginning of the seizures) consists of a blissful state of mental clarity/feeling of certainty. Such a state has also been described as a “religious” or mystical experience. While this form of epilepsy has long been recognized as a temporal lobe epilepsy, we have accumulated evidence converging toward the location of the symptomatogenic zone in the dorsal anterior insula during the 10 last years. The neurocognitive hypothesis for the genesis of a mental clarity is the suppression of the interoceptive prediction errors and of the unexpected surprise associated with any incoming internal or external signal, usually processed by the dorsal anterior insula. This mimics a perfect prediction of the world and induces a feeling of certainty. The ecstatic epilepsy is thus an amazing model for the role of anterior insula in uncertainty and surprise.

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Spontaneous Excitatory Currents and κ-Opioid Receptor Inhibition in Dentate Gyrus Are Increased in the Rat Pilocarpine Model of Temporal Lobe Epilepsy

Journal of Neurophysiology ◽

10.1152/jn.1997.78.4.1860 ◽

1997 ◽

Vol 78 (4) ◽

pp. 1860-1868 ◽

Cited By ~ 22

Author(s):

Michele L. Simmons ◽

Gregory W. Terman ◽

Charles Chavkin

Keyword(s):

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Opioid Receptor ◽

Temporal Lobe ◽

Mossy Fiber ◽

Perforant Path ◽

Mossy Fiber Sprouting ◽

Receptor Inhibition ◽

Excitatory Activity ◽

Pilocarpine Model

Simmons, Michele L., Gregory W. Terman, and Charles Chavkin. Spontaneous excitatory currents and κ-opioid receptor inhibition in dentate gyrus are increased in the rat pilocarpine model of temporal lobe epilepsy. J. Neurophysiol. 78: 1860–1868, 1997. Temporal lobe epilepsy is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of neuronal loss and aberrant growth of mossy fiber collaterals into the dentate gyrus inner molecular layer. We have used the rat pilocarpine model of temporal lobe epilepsy to study the functional consequences of mossy fiber sprouting on excitatory activity and κ-opioid receptor-mediated inhibition. Using the whole cell voltage-clamp technique, we found that abnormal excitatory activity was evident in granule cells of the dentate gyrus from pilocarpine-treated rats. The frequency of spontaneous excitatory postsynaptic currents (EPSCs) was increased greatly in cells from tissue in which significant mossy fiber sprouting had developed. In the presence of bicuculline, giant spontaneous EPSCs, with large amplitudes and long durations, were seen only in association with mossy fiber sprouting. Giant EPSCs also could be evoked by low-intensity stimulation of the perforant path. Mossy fibers release not only excitatory amino acids, but also opioid peptides. κ-Opioid receptor-mediated inhibition in normal Sprague-Dawley rats was seen only in hippocampal sections from the ventral pole. In pilocarpine-treated rats, however, kappa receptor-mediated effects were seen in both ventral and more dorsal sections. Thus in this model of temporal lobe epilepsy, several types of abnormal excitatory activity were observed, thereby supporting the idea that mossy fiber sprouting leads to recurrent excitatory connections. At the same time, inhibition of excitatory activity by κ-opioid receptors was increased, perhaps representing an endogenous anticonvulsant mechanism.

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