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Manual The Clinical Neurobiology of the Hippocampus: An integrative view

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However, in the rapidly growing field of hippocampal research, the clinical aspects of diseases that affect the hippocampus are greatly under-represented, and clinical approaches and concepts are scattered throughout various clinical and basic scientific disciplines. This book explores clinical approaches to the range of diseases that affect the hippocampus.

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It brings together and reviews the common methods, clinical findings, concepts, mechanisms and, where applicable, therapeutic strategies for these clinical approaches. The clinical spectrum of hippocampal dysfunction encompasses a wide range of neurological, behavioural, and psychiatric symptoms and surpasses the ability to encode, store, and retrieve information. The relevance of hippocampal involvement in clinical diseases goes beyond mere neuropsychological deficits and includes psychopathological states in various conditions, such as acute amnesic syndromes, Alzheimer's disease, temporal lobe epilepsy TLE , sleep, stroke medicine, limbic encephalitis, neurodevelopmental disorders, stress- and trauma-related disorders, depression, and schizophrenia.

Keywords: hippocampus , clinical approaches , hippocampal research , therapeutic strategies , clinical diseases , psychopathological states , depression. Forgot password? Don't have an account? All Rights Reserved. OSO version 0. University Press Scholarship Online.

The Clinical Neurobiology of the Hippocampus - Thorsten Bartsch - Oxford University Press

Sign in. Not registered? The function of the hippocampus has been extensively studied from a behavioral, biochemical and neuroanatomical perspective, establishing the hippocampus as an excellent model for studying the function of a protein. Cytoglobin Cygb was identified as the fourth vertebrate heme-globin in 5 , 6.

Cygb has, despite low sequence homology with the canonical hemoglobin and myoglobin, retained the classical globin fold and can reversibly bind oxygen and other diatomic gasses 7. Cygb is expressed in a number of tissues and is also found in neurons of the brain where Cygb is localized in the soma, neuronal processes and nuclei 8 , 9. Within the mouse brain, Cygb is expressed in distinct areas with large regional differences in the expression levels.

The areas with pronounced Cygb expression are the hippocampus, reticular thalamic nucleus RT , habenula, laterodorsal tegmental nucleus and the pedunculopontine tegmental nucleus 8 , 10 , The Cygb expression patterns in the mouse brain were recently determined to be identical in the rat and human brain, demonstrating that the rodent brain can be used as a translational model for studying Cygb in humans, at least at the anatomical level 12 , Furthermore, Cygb overexpression protects against ischemic cell death in vivo 21 , although not when expressed at endogenous levels In our previous studies, Cygb-immunoreactivity ir was shown to be highly co-localized with one of the enzymes producing NO, namely neuronal nitric oxide synthase nNOS , in the mouse brain 9 and found that the majority of the nNOS-ir neurons of the rat hippocampus co-localized with Cygb-ir However, due to the larger number of Cygb-ir cells in the hippocampus, the majority of Cygb-ir cells remain uncharacterized The aim of the present study was to extend our previous study 13 in the rat hippocampus by providing a detailed neurochemical phenotype of the Cygb-ir neurons in association with the subpopulation co-expressing nNOS.

Knowledge regarding the neurochemical phenotypes of neurons expressing the protein of interest can be a valuable tool, as it will allow the investigator to determine if the protein of interest is primarily co-localized with one other protein or groups of proteins associated with known specific functions or pathways.


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Six male Wistar rats g from Taconic Denmark , were used in the experiment. Animal care and all the experimental procedures were conducted in accordance to the principles of Laboratory Animal Care Law on Animal Experiments in Denmark, publication , November 23, and approved by the Faculty of Health, University of Copenhagen Copenhagen, Denmark.

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The IHC protocol has been described previously SOMA is a neuroendocrine peptide hormone and regulates a number of secondary hormones via its G protein-coupled receptors. VIP is a major regulatory peptide in the brain and is involved in a number of processes, including circadian and neuroendocrine control. PV is a calcium-binding protein involved in numerous physiological processes. HO-1 is an enzyme that catalyzes the degradation of heme groups to produce biliverdin, iron and the gas-neurotransmitter carbon monoxide.

When two rabbit primary antibodies were used in continuation, a previously described protocol 23 was used. Briefly, following the initial block of endogen peroxide with H 2 O 2 treatment, the first primary antibody, which was highly diluted, was detected with a biotin-conjugated donkey anti-rabbit code , dilution; Jackson Immunoresearch Laboratories, Inc.

The Clinical Neurobiology of the Hippocampus: An integrative view

The second primary antibody was detected with a donkey anti-rabbit Alexa The image analysis in the higher magnification, the images were captured by the spinning disk confocal section of the microscope. Intense Cygb-ir was observed throughout the rostral-caudal extend and in the majority of the hippocampal structures, with the highest density in the dentate gyrus DG and hilus Fig. In the pyramidal cell layer Py , in fields CA1—CA3, evident Cygb-ir was detected in the cell soma, nuclei and processes of the pyramidal cells Fig.

PV-ir interneurons and processes were observed in the same areas as Cygb-ir. SOMA-ir was highly expressed throughout the hippocampus Fig. Outside the hippocampus, such as the RT, a high degree of co-localization between Cygb-ir and the neurochemical marker, PV, was also observed Fig. D The merged image of A—C is shown. A high degree of co-localization was observed between Cygb-immunoreactivity ir red and PV-ir green throughout the hippocampus and the majority of the PV-ir neurons did not co-localize with nNOS-ir cyan.

The area within the white box is magnified in Fig. A high degree of co-localization is shown between Cygb-immunoreactivity ir red and HOir green in the DG. As for vasoactive intestinal peptide, SOMA-immunoreactivity ir green neurons primarily belonged to the sub-population of Cygb-ir red neurons, also co-localizing nNOS-ir cyan. Co-localization of cytoglobin Cygb -immunoreactivity ir and parvalbumin PV -ir in the reticular thalamic nucleus.


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C All the PV-ir neurons co-expressed with Cygb-ir. The images on the right side are higher magnifications of the area within the white square in A. The Z-stack image analysis of the areas within the white squares in Figs. High magnification images of the white squares in Figs. The yellow arrows D indicate that certain cells co-store Cygb and PV, the purple arrows indicate the cells co-storing Cygb and nNOS and the white arrow show a cell co-expressing all three.

The white vertical and horizontal lines indicate the Y-Z and X-Z axis, respectively.

Despite intensive research 32 over the past 12 years, the function of Cygb remains an enigma. To the best of our knowledge, the present study is the first detailed characterization of the neurochemical phenotype of Cygb-ir neurons in the rat hippocampus and can, in combination with other methods, contribute to an improved understanding of the Cygb function.

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Temporary inhibition of dorsal or ventral hippocampus by muscimol: Distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning. The hippocampus uses information just encountered to guide efficient ongoing behavior. Lydia T. Yee, David E. Warren, Joel L.

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