Comparative analysis of dentate gyrus from naive Wistar rats and human hippocampus using molecular tools

Much of the studies related to the hippocampus are aimed to elucidate the diseases which affect this structure, such as Mesial Temporal Lobe Epilepsy (MTLE) and Alzheimer’s disease (AD). However, to better understand the pathophysiology of these diseases, which are not fully elucidated, we must focus in other structures from the Hippocampal Formation, that can be involved with these mechanisms, such as the DG¹. The DG itself is also subdivided into dorsal and ventral in rodents and posterior and anterior in humans². Moreover, the neurodegenerative diseases, as others, are usually investigated using animal models, mainly rodents, due to its possibility of study the development of the diseases and not only its final stage³. However, despite its remarkable similarities with humans, it is necessary to evaluate the differences between the two species to validate the rodents as a suitable model for human pathologies. Therefore, here we present the comparative multi-OMICs analysis of the laser microdissected DG from rat and humans, intending to characterize and describe both species, validating the rat as a good animal model for human pathologies. We also present the comparative analysis of dorsal and ventral DG isolated from the rats.

Download Full-text

Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

Epilepsy Research and Treatment ◽

10.1155/2011/758407 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Julio Lachos ◽

Michela Zattoni ◽

Heinz-Gregor Wieser ◽

Jean-Marc Fritschy ◽

Thomas Langmann ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Temporal Lobe Epilepsy ◽

Gene Expression Profile ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Human Hippocampus ◽

Mesial Temporal Lobe ◽

Underlying Pathophysiology

One of the main putative causes of therapy refractory epilepsy in mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis is the overexpression of multidrug transporters (MDTs) at the blood-brain barrier (BBB). It steps up the removal of antiepileptic drugs (AEDs) out of the brain cells across the BBB resulting in a low concentration of AEDs within the target cells. Some of the mechanisms of AED resistance are most likely to be genetically determined. To obtain more information about the underlying pathophysiology of intractability in epilepsy, we compared the global gene expression profile of human hippocampus and hippocampal-derived microvascular endothelial cells from MTLE with HS patients and controls. At the level of MDT, a significant up-regulation was found for ABCB1 (P-gp), ABCB2, ABCB3, and ABCB4, which was mainly related to endothelial cells. The data on the MDT were validated and extended by quantitative RT-PCR. Surprisingly, inflammatory factors such as interleukins (IL-1α, IL-1β, IL-6, and IL-18) and cytokines (TNF-α and TGF-β1) were found to be up-regulated in hippocampal parenchyma. The overexpression of P-gp, IL-1β, and IL-6 was also confirmed by immunohistochemistry (IHC). Our results suggest that complex expression changes of ABC-transporters may play a decisive role in pharmacoresistance in MTLE. Further studies on the new and unexpected overexpression of inflammatory cytokines may unlock hitherto undiscovered pathways of the underlying pathophysiology of human MTLE.

Download Full-text

Neurocysticercosis and microscopic hippocampal dysplasia in a patient with refractory mesial temporal lobe epilepsy

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2006000200026 ◽

2006 ◽

Vol 64 (2a) ◽

pp. 309-313 ◽

Cited By ~ 14

Author(s):

Alexandre Valotta da Silva ◽

Heloise Helena Martins ◽

Carolina Mattos Marques ◽

Elza Marcia Targas Yacubian ◽

Américo Ceiki Sakamoto ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Refractory Epilepsy ◽

Hippocampal Formation ◽

Granular Cell ◽

Mesial Temporal Lobe Epilepsy ◽

Epidemiologic Studies ◽

Neuronal Markers ◽

Symptomatic Epilepsy ◽

Mesial Temporal Lobe

Epidemiologic studies suggest that neurocysticercosis (NC) is the main cause of symptomatic epilepsy in developing countries. The association between NC and mesial temporal lobe epilepsy (MTLE) has been reported by several authors. Recent data have shown that the presence of NC does not influence the clinical and pathological profile in MTLE patients and suggest that not all cysticercotic lesions are inevitably epileptogenic. We describe a 50-years-old woman with partial seizures due to NC which evolve to MTLE. The patient was submitted to a corticoamygdalohippocampectomy to treat refractory epilepsy. An immunohistochemical study using neuronal markers was made on hippocampal formation. Besides the typical aspects of Ammon's horn sclerosis (AHS), the microscopic examination demonstrates cellular features of hippocampal malformation including dysmorphic neurons and focal bilamination of granular cell layer. We suggest that, in this case, a developmental disorder lowered the threshold for the NC-induced seizures and contributed to the establishment of refractory epilepsy.

Download Full-text