Cornu Ammonis Subfields Research Articles

Epidermoid cyst involving the medial temporal lobe: Surgical pathologic features of the epileptogenic lesion

Epidermoid cysts in the middle fossa are rare and may involve the temporal lobe and lateral ventricle. Affected patients often suffer from seizures, but the pathomechanisms underlying the epileptogenic lesions have remained unclear. Here we report the surgical pathological features of the hippocampus in a 31-year-old woman with mesial temporal lobe epilepsy (mTLE), in whom an epidermoid cyst involving the right basal cistern and inferior horn of the lateral ventricle was evident. The ictal electrocorticogram indicated seizure onset at the parahippocampal gyrus. An anterior temporal lobectomy and amygdalohippocampectomy were performed. Histologically, the hippocampus showed marked atrophy with severe loss of pyramidal neurons in the cornu Ammonis subfields and granule cell loss in the dentate gyrus. At the ventricular surface of the hippocampus, there were small granulomatous lesions with spicularly anchored keratin substance. These features indicated multiple and chronic stab wounds by the cyst contents and consequent local inflammatory responses within the parenchyma. The predisposition to adhesion between the tumor and hippocampus may have caused neurons to develop abnormal irritability to certain chemical mediators present in the cyst. Epileptogenicity involving the atrophic hippocampus and medial temporal lobes nearby may have developed in association with these processes. This case appears to provide information that is useful for surgical planning in patients with mTLE and epidermoid cysts involving the medial temporal lobe.

Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders

Brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor (trkB-TK+) and glutamic acid decarboxylase (GAD67) mRNA levels have previously been found to be reduced in the prefrontal cortex of patients with schizophrenia. To determine whether this reduction extends to other brain regions, we measured the expression levels of BDNF, trkB-TK+ and GAD67 mRNA in regions of the hippocampus, including the dentate gyrus (DG), cornu ammonis subfields (CA1-4), subiculum and entorhinal cortex (EC) of individuals with schizophrenia, bipolar disorder, major depression and unaffected controls. In situ hybridization was performed on postmortem brain tissue obtained from the Stanley Foundation Consortium and analyzed using film-based quantification. Analyses of covariance comparing the expression of mRNA among all groups revealed a significant decrease in BDNF mRNA in CA4 in the bipolar disorder group compared with controls (33%). We found trkB-TK+ mRNA levels to be significantly reduced in CA4 in the schizophrenia group (36%) and in layer II of the EC in the bipolar disorder and major depression groups (28%, 21%, respectively) compared with controls. In addition, GAD67 mRNA levels were reduced in patients with schizophrenia in both the DG (23%) and CA4 (60%) compared with controls. Individuals with major depression also expressed significantly less GAD67 mRNA (44%) compared with controls in CA4 of the hippocampus. It is necessary to account for factors that influence the molecular preservation in postmortem brain tissue, including pH, postmortem interval and tissue storage time. Moreover, there are limitations to the sensitivity of the film-based method of quantification. Our findings show abnormal BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders, indicating that fundamental properties of hippocampal signalling transmission, plasticity and circuitry may be affected in individuals with these major mental illnesses.

Neurogranin phosphorylation fine-tunes long-term potentiation.

Learning-related potentiation of synaptic strength at Cornu ammonis subfield 1 (CA1) hippocampal excitatory synapses is dependent on neuronal activity and the activation of glutamate receptors. However, molecular mechanisms that regulate and fine-tune the expression of long-term potentiation (LTP) are not well understood. Recently it has been indicated that neurogranin (Ng), a neuron-specific, postsynaptic protein that is phosphorylated by protein kinase C, potentiates synaptic transmission in an LTP-like manner. Here, we report that a Ng mutant that is unable to be phosphorylated cannot potentiate synaptic transmission in rat CA1 hippocampal neurons and results in a submaximal expression of LTP. Our results provide the first evidence that the phosphorylation of Ng can regulate LTP expression.

Mesial temporal lobe epilepsy: Clinical and neuropathologic findings of familial and sporadic forms

To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of São Paulo School of Medicine at Ribeirão Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm's stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm's staining in the fascia dentata-inner molecular layer (p< 0.05). Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.

Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization.

Comparison of central corticosteroid receptor expression in male Lewis and Fischer rats

The histocompatible inbred Lewis (LEW) and Fischer (F344) rat strains exhibit marked phenotypic differences in the hormonal activity of the hypothalamic–pituitary–adrenal (HPA) axis. As such they provide an important comparative model for the study of HPA regulation including the central feedback regulation by the glucocorticoid transcription factors, the mineralocorticoid receptor (MR) and the glucocortiocoid receptor (GR). In adult male rats, basal nadir plasma corticosterone values were similar in the two strains whereas the amplitude and duration of the corticosterone response to restraint were significantly reduced in LEW. MR and GR mRNA expression were compared in LEW and F344 throughout the rostrocaudal extent of the hippocampus. Hippocampal MR expression was consistent throughout the rostrocaudal extent and similar in F344 and LEW males. Hippocampal GR expression was consistent throughout the rostrocaudal extent, but significantly greater in the rostral dentate gyrus and Cornu ammonis subfields in LEW males compared with F344 males. The LEW phenotype of relatively high hippocampal GR expression and HPA hypoactivity is shared by outbred rats exposed to neonatal handling and GR-overexpressing transgenic mice. Whether or not this relationship is causal, as well as the functional significance of the rostral-extent specific GR difference, remains to be elucidated.

Non-spatial acquisition and retention deficits following small excitotoxic lesions within the hippocampus in monkeys

Marmoset monkeys with excitotoxic lesions confined to cornu ammonis subfields 1–3, subiculum and pre-subiculum, but sparing the entorhinal cortex, were impaired on retention and learning of conditional object–choice discriminations. For each of these discriminations, the monkeys were required to choose one of two objects depending on which of two patterned backgrounds was used on each trial. Two styles of order of trial presentation were used: ‘random’ presentation which maximised the degree of interference between trials, and ‘runs’ presentation which was intended to encourage the monkeys to learn each component of the discrimination separately. Before surgery monkeys found the discriminations more difficult to learn when the trials were presented in the ‘runs’ style than when presented in the ‘random’ style suggesting that the task is best learnt by applying a conditional rule. After surgery a significant ‘group×style’ interaction indicated that the ‘runs’ style was especially difficult for the lesioned monkeys. From these results we suggest that the hippocampus is involved in learning about and remembering non-spatial, conditional relations between objects.