Neuroscience
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Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vulnerability of hippocampal subfields to AD processes, neuroimaging researchers have tried to capture corresponding morphological changes within the hippocampus. ⋯ However, controversies remain regarding changes in hippocampal subfield structure in normal aging and regarding correlations between specific subfield volume and memory abilities, very likely because of the strong methodological variability between studies. Overall, hippocampal subfield analysis has proven to be a promising technique in the study of AD. However, harmonization of segmentation protocols and studies on larger samples are needed to enable accurate comparisons between studies and to confirm the clinical utility of these techniques.
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Despite the ongoing fundamental controversy about the physiological function of sleep, there is general consensus that sleep benefits neuronal plasticity, which ultimately supports brain function and cognition. In agreement with this are numerous studies showing that sleep deprivation (SD) results in learning and memory impairments. ⋯ When restricted sleep becomes a chronic condition, it causes a reduction of hippocampal cell proliferation and neurogenesis, which may eventually lead to a reduction in hippocampal volume. Ultimately, by impairing hippocampal plasticity and function, chronically restricted and disrupted sleep contributes to cognitive disorders and psychiatric diseases.
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Epileptogenesis refers to the development and extension of tissue capable of generating spontaneous seizures, resulting in the development of an epileptic condition and/or progression of epilepsy after the condition is established. The hippocampus is the seizure-initiating zone in many epilepsy patients as well as in animal models of epilepsy. During epileptogenesis, the hippocampus undergoes structural changes, including mossy fiber sprouting; alterations in dendritic branching, spine density, and shape; and neurogenesis. ⋯ Here we review conventional and more advanced MRI methods for detecting hippocampal tissue changes related to epileptogenesis. In addition, we summarize how diffusion tensor imaging can reveal cellular damage and plasticity, even at the level of hippocampal subfields. Finally, we discuss challenges and future directions for using novel MRI techniques in the search of biomarkers associated with epileptogenesis after brain injury.
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Hippocampal anatomy and network organization are capable to generate drug-resistant temporal lobe epilepsy (TLE) in humans and particularly vulnerable to segmental neuronal cell loss. Surgical hippocampectomy has been proven successful in treatment and available human tissue specimens allow systematic clinico-pathological examination. Different patterns of hippocampal cell loss have been identified in TLE patients and are recently classified by the International League against Epilepsy (ILAE) into four distinct subtypes in order to stratify the heterogenous group of TLE patients also with respect to postsurgical outcome. Another important aim of the international consensus classification system of hippocampal sclerosis (HS) is to gain further insights into the morpho-functional organization of human memory frequently compromised in TLE patients.
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Environmental enrichment (EE), which mimics the wealth of sensory, motor and cognitive stimuli that arise through intense interactions with the ambient environment, results in enhanced hippocampal long-term potentiation (LTP) and spatial learning. A key molecular factor in the mediation of these changes is the brain-derived neurotrophic factor (BDNF). One of the downstream cascades that is activated by BDNF is the cascade linked to the small GTPase, Ras, that triggers mitogen-activated protein kinase (MAPK) activity and is part of the cAMP response element-binding protein (CREB) pathway that can lead to synaptic restructuring to support LTP. ⋯ In addition, EE results in an equivalent enhancement of LTP transgenics and Wts, coupled with a decrease in Ras activity to Wt levels. This suggests that permanent activation of Ras in neurons of synRas animals following EE results in an altered feedback regulation of endogenous Ras activity that is not a key factor in LTP enhancements. The maintenance of Ras within a physiological range may thus be required for the optimization of LTP in the hippocampus.