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      Distribution of choline acetyltransferase (ChAT) immunoreactivity in the brain of the teleost Cyprinus carpio

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          Abstract

          Cholinergic systems play a role in basic cerebral functions and its dysfunction is associated with deficit in neurodegenerative disease. Mechanisms involved in human brain diseases are often approached by using fish models, especially cyprinids, given basic similarities of the fish brain to that of mammals. In the present paper, the organization of central cholinergic systems have been described in the cyprinid Cyprinus carpio, the common carp, by using specific polyclonal antibodies against ChAT, the synthetic enzyme of acetylcholine, that is currently used as a specific marker for cholinergic neurons in all vertebrates. In this work, serial transverse sections of the brain and the spinal cord were immunostained for ChAT. Results showed that positive neurons are present in several nuclei of the forebrain, the midbrain, the hindbrain and the spinal cord. Moreover, ChAT-positive neurons were detected in the synencephalon and in the cerebellum. In addition to neuronal bodies, afferent varicose fibers were stained for ChAT in the ventral telencephalon, the preoptic area, the hypothalamus and the posterior tuberculum. No neuronal cell bodies were present in the telencephalon. The comparison of cholinergic distribution pattern in the Cyprinus carpio central nervous system has revealed similarities but also some interesting differences with other cyprinids. Our results provide additional information on the cholinergic system from a phylogenetic point of view and may add new perspectives to physiological roles of cholinergic system during evolution and the neuroanatomical basis of neurological diseases.

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          The cholinergic hypothesis of geriatric memory dysfunction.

          Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
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            Central cholinergic systems and cognition.

            The organization and possible functions of basal forebrain and pontine cholinergic systems are reviewed. Whereas the basal forebrain cholinergic neuronal projections likely subserve a common electrophysiological function, e.g. to boost signal-to-noise ratios in cortical target areas, this function has different effects on psychological processes dependent upon the neural network operations within these various cortical domains. Evidence is presented that (a) the nucleus basalis-neocortical cholinergic system contributes greatly to visual attentional function, but not to mnemonic processes per se; (b) the septohippocampal projection is involved in the modulation of short-term spatial (working) memory processes, perhaps by prolonging the neural representation of external stimuli within the hippocampus; and (c) the diagonal band-cingulate cortex cholinergic projection impacts on the ability to utilize response rules through conditional discrimination. We also suggest that nucleus basalis-amygdala cholinergic projections have a role in the retention of affective conditioning while brainstem cholinergic projections to the thalamus and midbrain dopamine neurons affect basic arousal processes (e.g. sleep-wake cycle) and behavioral activation, respectively. The possibilities and limitations of therapeutic interventions with procholinergic drugs in patients with Alzheimer's disease and other neurodegenerative disorders in which basal forebrain cholinergic neurons degenerate are also discussed.
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              Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer's disease.

              The nucleus basalis is located at the confluence of the limbic and reticular activating systems. It receives dopaminergic input from the ventral tegmental area/substantia nigra, serotonergic input from the raphe nuclei, and noradrenergic input from the nucleus locus coeruleus. Its cholinergic contingent, known as Ch4, provides the principal source of acetylcholine for the cerebral cortex and amygdala. More than half of presynaptic varicosities along its cholinergic axons make traditional synaptic contacts with cortical neurons. Limbic and paralimbic cortices of the brain receive the heaviest cholinergic input from Ch4 and are also the principal sources of reciprocal cortical projections back to the nucleus basalis. This limbic affiliation explains the role of the nucleus basalis in modulating the impact and memorability of incoming sensory information. The anatomical continuity of the nucleus basalis with other basomedial limbic structures may underlie its early and high vulnerability to the tauopathy and neurofibrillary degeneration of Alzheimer's disease. The tauopathy in Ch4 eventually leads to the degeneration of the cholinergic axons that it sends to the cerebral cortex. The early involvement of Ch4 has a magnifying effect on Alzheimer's pathology, because neurofibrillary degeneration in a small number of neurons can perturb neurotransmission in all cortical areas. Although the exact contribution of the Ch4 lesion to the cognitive changes of Alzheimer's disease remains poorly understood, the cholinergic circuitry of the nucleus basalis is emerging as one of the most strategically positioned and behaviorally consequential modulatory systems of the human cerebral cortex. J. Comp. Neurol. 521:4124-4144, 2013. © 2013 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                Eur J Histochem
                EJH
                European Journal of Histochemistry : EJH
                PAGEPress Publications, Pavia, Italy
                1121-760X
                2038-8306
                24 July 2018
                24 July 2018
                : 62
                : 3
                : 2932
                Affiliations
                [1 ]Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome
                [2 ]Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome , Italy
                Author notes
                Sapienza University of Rome, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Via Alfonso Borelli 50, 00161 Rome, Italy. arianna.casini@ 123456uniroma1.it

                Contributions: AC, CC, RV, study concept and design; AC, RV, data acquisition; AC, CC, analysis and interpretation of data; AC, RV, MT, CC, drafting of the article; MT, obtained funding; CC, study supervision. All authors had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

                Conflict of interest: The authors declare no conflict of interest.

                Article
                10.4081/ejh.2018.2932
                6060486
                30043595
                7e888e43-b2ee-4d90-8d4b-9bc830bf9452
                ©Copyright A. Casini et al., 2018

                This work is licensed under a Creative Commons Attribution NonCommercial 4.0 License (CC BY-NC 4.0).

                History
                : 27 March 2018
                : 06 July 2018
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 90, Pages: 12
                Funding
                Funding: This study was supported by the Sapienza University of Rome (Progetti di ricerca 2016 to MT).
                Categories
                Original Paper

                Clinical chemistry
                chat,immunohistochemistry,cyprinid,central nervous system
                Clinical chemistry
                chat, immunohistochemistry, cyprinid, central nervous system

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