https://caltcm.memberclicks.net/assets/documents/acc_aha_chf_2013_guidelines.pdf

2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

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.

https://science.sciencemag.org/content/sci/217/4558/408.full.pdf

The Cholinergic Hypothesis of Geriatric Memory Dysfunction

We examine two different descriptions of the behavioral functions of the hippocampal system. One emphasizes spatially organized behaviors, especially those using cognitive maps. The other emphasizes memory, particularly working memory, a short-term memory that requires iexible stimulus-response associations and is highly susceptible to interference. The predictive value of the spatial and memory descriptions were evaluated by testing rats with damage to the hippocampal system in a series of experiments, independently manipulating the spatial and memory characteristics of a behavioral task. No dissociations were found when the spatial characteristics of the stimuli to be remembered were changed; lesions produced a similar deficit in both spatial and nonspatial test procedures, indicating that the hippocampus was similarly involved regardless of the spatial nature of the task. In contrast, a marked dissociation was found when the memory requirements were altered. Rats with lesions were able to perform accurately in tasks that could be solved exclusively on the basis of reference memory. They performed at chance levels and showed no signs of recovery even with extensive postoperative training in tasks that required working memory. In one experiment all the characteristics of the reference memory and working memory procedures were identical except the type of memory required. Consequently, the behavioral dissociation cannot be explained by differences in attention, motivation, response inhibition, or the type of stimuli to be remembered. As a result of these experiments we propose that the hippocampus is selectively involved in behaviors that require working memory, irrespective of the type of material (spatial or nonspatial) that is to be processed by that memory.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F9ABFA09F5AC96A64D15572521BD2C6C/S0140525X00062713a.pdf/div-class-title-hippocampus-space-and-memory-div.pdf

Hippocampus, space, and memory

The acute effects of corticosteroids on cognition: integration of animal and human model studies

The hippocampus and contextual retrieval of information from memory: A theory

Impairment of shuttle box avoidance learning following prolonged alcohol consumption in rats.

Hypothermia after acute ethanol and benzyl alcohol administration.

Effect of hippocampal lesions and intertrial interval on single-alternation performance in the rat.

This study tests the hypothesis that glutamate receptors are altered in the brains of alcoholics as a result of chronic alcohol neurotoxicity. Release of the neurotransmitter glutamate after seizures or brain ischemia may damage postsynaptic neurons by increasing calcium flux through N-methyl-D-aspartate (NMDA) receptor-gated ion channels. Alcohol has two opposite effects on glutamate receptor ion channel complexes, depending upon the duration of exposure. Acute exposure to alcohol inhibits ion flow through these receptor-channel complexes, whereas chronic exposure up-regulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of up-regulated channels, thereby making postsynaptic neurons vulnerable to excitotoxic damage. We selected 13 histologically normal brains from alcoholics and 13 brains from controls from our brain bank that were matched for age, postmortem interval, and storage time. Maximal binding and affinities of glutamate receptor subtypes were determined by quantitative autoradiography in the superior frontal cortex, Brodmann area 8. The most alcohol-sensitive subtype, NMDA receptor-channel complexes, were modestly but consistently increased in alcoholics. This included agonist sites (NMDA-sensitive [3H]glutamate), and antagonist site ([3H]CGP-39653), and a [3H]MK-801 binding site in the channel interior, although the increase of the latter did not reach statistical significance. Age, autopsy delay, time in storage, liver diseases, thiamine deficiency, CNS medications, and various diseases causing acute and chronic hypoxia did not significantly affect receptor density or affinity. In contrast, the other two glutamate channel subtypes, AMPA and kainate receptors, were not significantly different in alcoholics compared with controls. In conclusion, chronic alcoholism moderately increases the density of the NMDA subtype of glutamate receptors in the frontal cortex. This up-regulation may represent a stage of alcohol-induced chronic neurotoxicity.

Glutamate Receptors in the Frontal Cortex of Alcoholics

The brain damage of chronic alcoholics has been assumed to be a consequence of malnutrition and of thiamine deficiency. In order to explore the possibility that brain damage can be the result of ethanol toxicity per se without the additional effect of nutritional deficiency, the following study was designed. Ethanol was administered to three-month-old female C57BL/6J mice in the form of a nutritionally adequate liquid diet which contained 35% of its caloric content in the form of ethanol. Control groups were fed either an equivalent liquid diet containing sucrose in amounts which were isocaloric with the ethanol used in the test group or laboratory chow. Two weeks after ethanol (or sucrose) had been omitted from the diet, the mice were tested in a shuttle box for acquisition of an avoidance task consisting of 30 trials daily. There was progressive impairment of learning in mice consuming ethanol from three to five months in comparison with the control groups. This learning deficit persisted for at least 4½ months after ethanol feeding had been discontinued. Nearly lethal food deprivation did not cause impairment of learning under the conditions of this experiment. Autopsy studies after the conclusion of performance testing revealed essentially no damage to liver, heart, kidney or lungs. It was concluded that progressive impairment of learning performance was caused by prolonged ethanol consumption per se and not by malnutrition.

Gerhard Freund

Papers

Impairment of shuttle box avoidance learning following prolonged alcohol consumption in rats.

Hypothermia after acute ethanol and benzyl alcohol administration.

Effect of hippocampal lesions and intertrial interval on single-alternation performance in the rat.

Glutamate Receptors in the Frontal Cortex of Alcoholics

Impairment of avoidance learning by prolonged ethanol consumption in mice.