Abstract
Accumulating evidence points to the association of epilepsy, particularly, temporal lobe epilepsy (TLE), with psychiatric disorders, such as schizophrenia. Among these illnesses, the hippocampus is considered the regional focal point of the brain, playing an important role in cognition, psychosis, and seizure activity and potentially suggesting common etiologies and pathophysiology of TLE and schizophrenia. In the present review, we overview abnormal network connectivity between the dentate gyrus (DG) and the Cornus Ammonis area 3 (CA3) subregions of the hippocampus relative to the induction of epilepsy and schizophrenia. In light of our recent finding on the misguidance of hippocampal mossy fiber projection in the rodent model of schizophrenia, we discuss whether ectopic mossy fiber projection is a commonality in order to evoke TLE as well as symptoms related to schizophrenia.
Highlights
Numerous clinical studies report that up to 30% of individuals with epilepsy often present distinct psychiatric symptoms, such as intellectual aurae, dreamy states, complex visual illusion, and auditory hallucinations [1,2,3,4,5,6,7,8,9,10]
Consistent with this observation, hippocampal postmortem brain analyses from individuals with schizophrenia revealed elevated expression of brain-derived neurotrophic factor (BDNF) mRNA as well as GluN2B-containing NMDA receptors, and postsynaptic density protein 95 (PSD-95) proteins, in the Cornus Ammonis area 3 (CA3) subregion, all of which indicate an increase in synaptic strength through, in part, increasing levels of molecules involved in glutamatergic synaptic transmission [39,40,41]
It is becoming evident that Temporal lobe epilepsy (TLE) and schizophrenia share commonality in various aspects, leading us to postulate similar etiology of these disorders
Summary
Numerous clinical studies report that up to 30% of individuals with epilepsy often present distinct psychiatric symptoms, such as intellectual aurae, dreamy states, complex visual illusion, and auditory hallucinations [1,2,3,4,5,6,7,8,9,10]. Glutamatergic dysfunction is becoming a well-accepted concept underlying the pathophysiology of schizophrenia, it is largely elusive exactly how altered glutamate signaling initiates and manifests schizophrenic illness Consistent with this observation, hippocampal postmortem brain analyses from individuals with schizophrenia revealed elevated expression of brain-derived neurotrophic factor (BDNF) mRNA as well as GluN2B-containing NMDA receptors, and postsynaptic density protein 95 (PSD-95) proteins, in the CA3 subregion, all of which indicate an increase in synaptic strength through, in part, increasing levels of molecules involved in glutamatergic synaptic transmission [39,40,41]. The abnormal collaterals ectopically innervate from the hilus to the molecular layer of the DG, making contacts with apical dendrites of granule cells and forming extra excitatory synapses This abnormal synaptic morphology is called mossy fiber sprouting, which occurs in animal models of epilepsy, and in individuals with TLE and bipolar disorder [57,58,59,60,61, 76]. The role of aberrant mossy fiber projection is unclear, one suggests that synapses produced by mossy fiber sprouting are functionally active, because axon selection depends on excitatory pre- and postsynaptic activity, resulting in hyperexcitation of the DG and the CA3, the origin of epileptogenesis [45,46,47,48,49]
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