Interictal psychosis following temporal lobe surgery: dentate gyrus pathology

2014 ◽  
Vol 44 (14) ◽  
pp. 3037-3049 ◽  
Author(s):  
M. Thom ◽  
M. Kensche ◽  
J. Maynard ◽  
J. Liu ◽  
C. Reeves ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Granule Cell ◽  
Cellular Response ◽  
Granule Cells ◽  
De Novo ◽  
Hippocampal Sclerosis ◽  
Mossy Fibre ◽  
Cannabinoid Type 1 Receptor ◽  
Cell Dispersion

BackgroundDe novointerictal psychosis, albeit uncommon, can develop in patients following temporal lobe surgery for epilepsy. Pathological alterations of the dentate gyrus, including cytoarchitectural changes, immaturity and axonal reorganization that occur in epilepsy, may also underpin co-morbid psychiatric disorders. Our aim was to study candidate pathways that may be associated with the development of interictal psychosis post-operatively in patients with hippocampal sclerosis (HS).MethodA total of 11 patients with HS who developed interictal psychosis (HS-P) post-operatively were compared with a matched surgical HS group without psychosis (HS-NP). Resected tissues were investigated for the extent of granule cell dispersion, mossy fibre sprouting and calbindin expression in the granule cells. We quantified doublecortin, mini-chromosome maintenance protein 2 (MCM2) and reelin-expressing neuronal populations in the dentate gyrus as well as the distribution of cannabinoid type 1 receptor (CBR1).ResultsThe patterns of neuronal loss and gliosis were similar in both groups. HS-P patients demonstrated less mossy fibre sprouting and granule cell dispersion (p < 0.01) and more frequent reduction in calbindin expression in granule cells. There were no group differences in the densities of immature MCM2, doublecortin and reelin-positive cells. CBR1 labelling was significantly lower in Cornu ammonis area CA4 relative to other subfields (p < 0.01); although reduced staining in all hippocampal regions was noted in HS-P compared with HS-NP patients, the differences were not statistically significant.ConclusionsThe alterations in dentate gyrus pathology found in HS-P patients could indicate underlying differences in the cellular response to seizures. These mechanisms may predispose to the development of psychosis in epilepsy and warrant further investigation.

Balloon cells associated with granule cell dispersion in the dentate gyrus in hippocampal sclerosis

2008 ◽  
Vol 115 (6) ◽  
pp. 697-700 ◽  
Author(s):  
M. Thom ◽  
L. Martinian ◽  
L. O. Caboclo ◽  
A. W. McEvoy ◽  
S. M. Sisodiya
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Hippocampal Sclerosis ◽  
Balloon Cells ◽  
Cell Dispersion

Dentate gyrus and hilus transection blocks seizure propagation and granule cell dispersion in a mouse model for mesial temporal lobe epilepsy

Hippocampus ◽  
2011 ◽  
Vol 21 (3) ◽  
pp. 334-343 ◽  
Author(s):  
Johan Pallud ◽  
Ute Häussler ◽  
Mélanie Langlois ◽  
Sophie Hamelin ◽  
Bertrand Devaux ◽  
...  
Keyword(s):  
Mouse Model ◽  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Granule Cell ◽  
Mesial Temporal Lobe Epilepsy ◽  
Cell Dispersion ◽  
Mesial Temporal Lobe ◽  
Seizure Propagation

scholarly journals Hippocampal Transplants of Fetal GABAergic Progenitors Regulate Adult Neurogenesis in Mice with Temporal Lobe Epilepsy

2022 ◽  
Author(s):  
Muhammad Nauman Arshad ◽  
Simon Oppenheimer ◽  
Jaye Jeong ◽  
Bilge Buyukdemirtas ◽  
Janice R Naegele
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Adult Neurogenesis ◽  
Granule Cell ◽  
Granule Cells ◽  
Granule Cell Layer ◽  
Spontaneous Seizures ◽  
Type 3

GABAergic interneurons within the dentate gyrus of the hippocampus regulate adult neurogenesis, including proliferation, migration, and maturation of new granule cells born in the subgranular zone (SGZ) of the dentate gyrus (DG). In temporal lobe epilepsy (TLE), some adult-born granule cells migrate ectopically into the hilus, and these cells contribute to increased hyperexcitability and seizures. Yet, transplanting embryonic day 13.5 fetal mouse medial ganglionic eminence (MGE) GABAergic progenitors into the hippocampus of mice with TLE ameliorates spontaneous seizures, due in part, to increased postsynaptic inhibition of adult-born granule cells. Here, we asked whether MGE progenitor transplantation affects earlier stages of adult neurogenesis, by comparing patterns of neurogenesis in naive mice and epileptic (TLE) mice, with or without MGE transplants. In naive and TLE mice, transplanted MGE cells showed comparable migration and process outgrowth. However, in TLE mice with MGE transplants, fewer adult-born Type 3 progenitors migrated ectopically. Furthermore, more Type 3 progenitors survived and migrated into the granule cell layer (GCL), as determined by immunostaining for doublecortin or the thymidine analogue, bromodeoxyuridine (BrdU). To determine whether MGE transplants affected earlier stages of adult neurogenesis, we compared proliferation in the SGZ two-hours after pulse labeling with BrdU in naive vs. TLE mice and found no significant differences. Furthermore, MGE progenitor transplantation had no effect on cell proliferation in the SGZ. Moreover, when compared to naive mice, TLE mice showed increases in inverted Type 1 progenitors and Type 2 progenitors, concomitant with a decrease in the normally oriented radial Type 1 progenitors. Strikingly, these alterations were abrogated by MGE transplantation. Thus, MGE transplants appear to reverse seizure-induced abnormalities in adult neurogenesis by increasing differentiation and radial migration of adult-born granule cell progenitors, outcomes that may ameliorate seizures.

scholarly journals Circuit-based interventions in the dentate gyrus rescue epilepsy-associated cognitive dysfunction

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2705-2721 ◽  
Author(s):  
Julia B Kahn ◽  
Russell G Port ◽  
Cuiyong Yue ◽  
Hajime Takano ◽  
Douglas A Coulter
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Cognitive Dysfunction ◽  
Temporal Lobe ◽  
Granule Cell ◽  
Granule Cells ◽  
Dorsal Hippocampus ◽  
Cell Activity ◽  
Downstream Target ◽  
Behavioural Performance

Abstract Temporal lobe epilepsy is associated with significant structural pathology in the hippocampus. In the dentate gyrus, the summative effect of these pathologies is massive hyperexcitability in the granule cells, generating both increased seizure susceptibility and cognitive deficits. To date, therapeutic approaches have failed to improve the cognitive symptoms in fully developed, chronic epilepsy. As the dentate’s principal signalling population, the granule cells’ aggregate excitability has the potential to provide a mechanistically-independent downstream target. We examined whether normalizing epilepsy-associated granule cell hyperexcitability—without correcting the underlying structural circuit disruptions—would constitute an effective therapeutic approach for cognitive dysfunction. In the systemic pilocarpine mouse model of temporal lobe epilepsy, the epileptic dentate gyrus excessively recruits granule cells in behavioural contexts, not just during seizure events, and these mice fail to perform on a dentate-mediated spatial discrimination task. Acutely reducing dorsal granule cell hyperactivity in chronically epileptic mice via either of two distinct inhibitory chemogenetic receptors rescued behavioural performance such that they responded comparably to wild type mice. Furthermore, recreating granule cell hyperexcitability in control mice via excitatory chemogenetic receptors, without altering normal circuit anatomy, recapitulated spatial memory deficits observed in epileptic mice. However, making the granule cells overly quiescent in both epileptic and control mice again disrupted behavioural performance. These bidirectional manipulations reveal that there is a permissive excitability window for granule cells that is necessary to support successful behavioural performance. Chemogenetic effects were specific to the targeted dorsal hippocampus, as hippocampal-independent and ventral hippocampal-dependent behaviours remained unaffected. Fos expression demonstrated that chemogenetics can modulate granule cell recruitment via behaviourally relevant inputs. Rather than driving cell activity deterministically or spontaneously, chemogenetic intervention merely modulates the behaviourally permissive activity window in which the circuit operates. We conclude that restoring appropriate principal cell tuning via circuit-based therapies, irrespective of the mechanisms generating the disease-related hyperactivity, is a promising translational approach.

scholarly journals Increased Reelin Promoter Methylation Is Associated With Granule Cell Dispersion in Human Temporal Lobe Epilepsy

2009 ◽  
Vol 68 (4) ◽  
pp. 356-364 ◽  
Author(s):  
Katja Kobow ◽  
Ina Jeske ◽  
Michelle Hildebrandt ◽  
Jan Hauke ◽  
Eric Hahnen ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Granule Cell ◽  
Promoter Methylation ◽  
Cell Dispersion ◽  
Human Temporal Lobe

Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy

2009 ◽  
Vol 111 (6) ◽  
pp. 1237-1247 ◽  
Author(s):  
László Seress ◽  
Hajnalka Ábrahám ◽  
Zsolt Horváth ◽  
Tamás Dóczi ◽  
József Janszky ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Pyramidal Neurons ◽  
Hippocampal Sclerosis ◽  
Mesial Temporal Lobe Epilepsy ◽  
Drug Resistant ◽  
Hippocampal Dentate Gyrus ◽  
Mossy Cells ◽  
Mesial Temporal Lobe

Object Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Methods Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Results Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. Conclusions In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

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