The effect of vasopressin on memory processes in Macaca fascicularis]

The role of vasopressin (arginin-vasopressin) in the regulation of conditioned instrumental food-procuring reactions and different kinds of memory such as delayed reflexes, image, short-, and long-time memory was studied in monkeys. Motor and autonomic effects of vasopressin were assessed. It was found that in monkeys, vasopressin administration differently affected the simple conditioned food-procuring reactions and memory. During functional disorders of the higher nervous activity, vasopressin was more efficient in its action on memory and its restoration. Formation of two types of vasopressin effects on the higher nervous activity in evolution of mammals is discussed.     

Comparative Study of Neurochemical Compensation of Disturbed Brain Functions in Mammals

In a comparative row of mammals (hedgehogs, rabbits, monkeys), the role of the opioid neuropeptide Met-encephalin (ME) and the hypothalamic neurohormone vasopressin (VP) was studied in possibility of compensation of disturbed higher nervous functions in organic and functional pathologies of the higher nervous activity. Administration of ME and VP under conditions of destruction of neocortex in hedgehogs was found to restore predominantly congenital forms of the nervous activity. In rabbits, on administration of VP, a tendency is revealed for restoration of acquired forms of the nervous activity; however, it is of a limited character. On administration of ME and VP under conditions of functional pathology a similar regularity in restoration of disturbed higher nervous functions is observed. Injection of ME and VP to hedgehogs produced a more pronounced and longer effect on unconditioned reflexes. The effect of low doses of VP on HNA is of short-term, generally facilitating character. In rabbits, on the background of VP, the memory processes (trace conditioned responses) are briefly restored and are enhanced. In monkeys, the effect of ME and VP on acquired forms of the nervous activity and on various functional systems is of differential character. The VP compensatory effects are more pronounced after administration of low VP doses. The effects of ME and VP on congenital forms of the nervous activity are negligible. The established regularities are discussed and interpreted from the viewpoint of the concepts postulated by A.I. Karamyan about evolution of the compensatory brain activity, evolution of neocortex, and an increase of its neuroplasticity.     

Peculiarities of Neurohormonal Modulation of Memory and Learning Processes in Young and Old Monkeys <Emphasis Type="Italic">Macaca mulatta</Emphasis>

Comparative data are presented about peculiarities of neurohormonal regulation of the memory and learning processes in young and old monkeys Macaca mulatta. It is shown that the hypothalamic neurohormones, vasopressin and thyroliberine, produce on the whole a unidirectional facilitating effect on the inherited and simple forms of the nervous activity in young and old animals. It is established that vasopressin, thyroliberine, and ACTH_4–10 participate differently in regulation and compensation of disturbed higher nervous functions in old monkeys. The compensatory effects of vasopressin are more pronounced at intranasal administration of its ultrasmall (0.01 jg/kg) doses. The thyroliberine administration had the longer and more expressed disinhibition effect on the conditional reflex memory in old monkeys, as compared with young ones. The question is discussed about different effects of vasopressin and thyroliberine on the higher nervous functions in young and old monkeys from the point of view of cytoarchitectonic changes in the neocortex and of immunohistochemical changes in the hypothalamus nuclear structures.     

Evolution of tool handling activity in monkeys

Main experimental data are presented which have been obtained on lower and higher monkeys. New understanding is suggested of regularities of interaction of primates with the environmental objects. The data are discussed in relation to historic and ontogenetic development of working activity in man.     

Effect of neurosteroid dehydroepiandrosterone on the higher nervous activity of old non-human primates

The results of studies on the biological effects of the prolonged administration of physiological doses of dehydroepiandrosterone (DHEA) on behavior and state of the higher nervous activity (HNA) in old rhesus macaques that had reached the limit of biological age are presented. HNA was investigated using the procedure of motor-alimentary conditioned reflexes, which allows assessing the long-term (conditioned-reflex) memory in animals. The state of short-term (working) memory was evaluated using the test of delayed response performance. DHEA was administered intramuscularly in peach oil at a dose of 1 mg/kg every two days for three months. DHEA at the doses used improved HNA and balanced the excitatory and inhibitory processes in the brain. The motor activity and alimentary motivation were increased. The woolliness lost was restored in old monkeys under the action of DHEA; this effect persisting for a year.     

Physiological analysis of the relation between the conditioned reflex and image memory in monkeys and preschool children

Interaction of short-term and long-term memory processes is subjected to phylo- and ontogenetic changes. Progressive development includes differentiation and independent manifestation of these memory forms together with formation of a more complex pattern of interaction between the latter.     

Cataractogenic and lethal effect of selenite in rats during postnatal ontogenesis.

Male rats aged 5, 10, 15, 20, 30, 40, 50 and 60 days were injected with a single dose of sodium selenite (20 or 40 mumol/kg b.w.). For two months after the injection, all the rats were observed daily for mortality (acute up to 24 h after the injection, subacute 2--7 days after) and the incidence of permanent and intermittent cataract. With the higher dose, both forms of lethal effect were found to shift to earlier phases of ontogenetic development, subacute mortality appearing sooner than acute mortality. The cataractogenic effect produced by the administration of both 20 and 40 mumol/kg b.w. dependent on the age of the experimental animals. It appeared only in the early phases of ontogenetic development (up to the age of 15 days); cataract was not observed during later development.     

Some Evolutionary Aspects of the Food-Procuring Group Behavior in Phylogenesis of Primates

The peculiarities were studied of the intragroup competitive and cooperative behavior of primates differing by the level of phylogenetic development, beginning from low-organized species of the higher primates to high-organized anthropoid monkeys (Callithrix jacchus, Cebus apella, Macaca mulatta, Papio hamaofrijas, Pan troglodytes). It has been shown that in all monkeys, under conditions of competitive feeding situation, there were changes of the complex behavioral forms observed at individual learning. Under conditions of the activity in pairs, the females of platyrrhine (New World) and lower narrow-nose (Old World) monkeys lost the possibility to realize the skill and food needs, so the programmed tasks were solved predominantly by the males. In chimpanzees, the change of indices of instrumental activity involved to the equal degree the male and female, and solution of the alternation task was higher in individual experiments. The age differences were revealed in the competitive behavior of chimpanzees in group. The realization of formed skills depended on the complex of factors including the requirements dominating in the given situation and the age and typological peculiarities, as well as the social rank of each monkey in the community. In rhesus macaques the capability for cooperative interaction was revealed under conditions of complex operant activity.     

Somatosensory evoked potentials of median and tibial nerves in rhesus monkeys (Macaca mulatta) under captivity: influence of ontogenic status in neonatal, infant, young, adult, and senile stages

Background Somatosensory evoked potentials (SEPs) constitute a useful neurophysiologic tool commonly used to assess the functionality and developmental degree of the nervous system. Objective To analyze somatosensory pathways of the Macaca mulatta species throughout different ontogenetic statuses. Methods Twenty non‐human primates were divided into five age‐dependant groups. Recording of SEPs was executed by stimulation of lower limb at the tibial nerve and upper limb and recorded at the median nerve. Results Two wave series were observed for all groups for both limbs studied. Significant differences were found at the upper right limb at C4, C7 and also for the antecubital fossa site. The lower limbs showed a single significant right‐wing deflection. Conclusions Differences found in signals generated by the nervous system in response to somatosensory stimuli among the studied groups are thought to be developmental in origin, as the most remarkable deviations were seen in younger monkeys.     

Features of the formation and dynamics of short-term image memory in the rat

Direct and indirect methods of delayed reactions showed that short-term image memory of rats elaborated on the basis of conditioned signals in poorly developed and its duration is not more than 1 s. While testing this memory, changes in the behaviour were seen, pointing to the development of "hard state" in the higher nervous activity of animals. Short-term image memory based on complex perception was shown to be well developed in rats, and by many characteristics it approximated to the memory of highly organized animals. The ability to reproduce the short-term image memory on the basis of conditioned signals is supposed to be a complex form of psychonervous activity of animals, and in rodents it appears to be at an initial stage of development.     

Comparative aspects of a study of the self-regulation of higher nervous activity in experimental neuroses in dogs, cats and rats

The higher nervous activity has been studied by means of motor-alimentary conditioned reflexes and delayed reactions in dogs, cats and albino rats at early stages of development of experimental informational neurosis. It was shown that formation of stable pathological reactions is preceeded by self- regulational activity of the brain directed towards elimination of a pathological situation, as well as to the increase of the stability of the nervous system to pathogenic agents. Comparative studies on rodents and predatory animals indicate that in different species the same pathogenic effects on the brain may elicit different forms of self-regulation of the higher nervous activity.     

Comparative pathology of higher nervous activity

In experiments with defensive behaviour, using multiparametric recording of indices, studies have been made on the origin and development of pathological disturbances in the higher nervous activity of insectivores, carnivores and primates during presentation of difficult conditioned reflex problems or extreme stimulation. It was found that elaboration of absolute differentiation retarded conditioned reactions with a delay of 25 s in insectivores is a difficult task which results in pathological changes in the higher nervous activity. In hedgehogs, neurotic changes are immediate, all the investigated indices being affected. In carnivores, especially in primates, the onset of evident pathological changes is preceded by a long preneurotic period, i.e. a stage of self-regulation. In pathological process, more corticalized forms of the nervous activity are initially involved. Common features and differences in the development of pathological changes in the higher nervous activity among mammals are discussed.     

Age dependent typology of central nervous system activity in school children]

The age peculiarities of higher nervous activity (HNA) have been studied in 777 1st-10th form pupils at school of general education. Heterogeneity and nonuniformity of changes in indices are peculiar to age dynamics of HNA. The most intensive changes are stated in junior and senior forms.     

Aging in the musculoskeletal system of rhesus monkeys: I. Passive joint excursion

In order to describe ontogenetic change in the musculoskeletal system of rhesus monkeys, 126 Macaca mulatta from Cayo Santiago, ranging in age from 7 months to 21 years, were examined under anesthesia. Passive joint excursions were measured at the wrist, elbow, shoulder, hip, and knee. Mean ranges of excursion at these joints differed significantly between age groups and by sex. The potential for most movements appeared to decrease approximately 25 degrees over the first two decades of the macaque life span, and males generally showed less potential for movement than females in all age groups. These results are similar to those obtained for humans and are consistent with patterns of positional behavior, trauma, and osteoarthritis observed in this rhesus monkey population. Thus, to fully describe the locomotor strategy of rhesus monkeys, age- and sex-related variation in locomotor anatomy and functional capacity must be considered.     

Ontogenetic patterns of frequency-power spectra elicited by flickering light in children: a comparative study of evoked and background EEGs.

Frequency-power spectra of the EEG evoked by repeptitive photic stimulation and of the background EEG were studied during childhood in 43 awake subjects aged between 2 months and 14 years. EEG activity was recorded from the middle parieto-occipital region with the aid of a 1-channel analyzer Lysograf-Alvar, analysing 16 frequencies in the range from 2 to 28 c/sec. The responsiveness of the central nervous system to flickering light improved in the course of childhood in parallel with the significant decline of delta activity and with the prominent increase of alpha intensity in the resting EEG. The 4th month of life appeared to be a marked turning point in the development of evoked and background EEGs. From that age, the bioelectric power at the flash rate corresponding to photic "driving" began to increase together with the highest and optimal driving frequencies. The flash rate, at which evoked potentials changed into the "driven" rhythm, also shifted towards higher frequencies. Subsequently, the amount of energy in the resting EEG increased significantly within the theta, alpha and beta bands and, on the contrary, a prominent decline was observed in the delta range. Marked ontogenetic changes at this age closely coincided with the rapid development of exogenous fibres in the occipital cortex, including the thalamo-cortical conncetions, and fibres of the neuropil in cortical layer I, which might play an important role in the genesis of background and "driven" in the occipital region.     

The comparative action of relanium and oxytocin on higher nervous activity in lower monkeys]

Effects of relanium and oxytocin on higher nervous activity was studied in four rhesus monkeys (Macaca mulatta) and two baboons (Papio hamadryas). During observation of the animals in enclosure tranquilizing effect was seen only after relanium administration. Under the same conditions oxytocin practically did not change the general behaviour pattern of monkeys. However, steady behavioural transformations were observed under the conditions of competitive food-procuring behaviour and during the operant goal-directed reaction. Decreasing aggressiveness of dominants oxytocin in contrast to relanium had no negative effect upon their general motor activity and sensory perception. Differences in effects of the tranquilizer and the peptide were seen also at the unit activity level of the neurons. The first drug lowered the unit activity level and the degree of the functional connections in neuronal populations in a number of cortical structures. Administration of the second one led to selective shifts of the unit activity mainly in the frontal cortex of the monkeys.     

Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis)

We compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. Eighteen cynomolgus monkeys—6 young (4–9 years), 6 middle-aged (10–19 years), and 6 old (above 20 years)—were tested. In general, the old monkeys scored significantly worse than did the animals in the two other age groups. Longer delays between stimulus presentation and response increased the performance differences between the old and younger monkeys. The old monkeys in particular showed signs of impaired visuo-spatial memory and deteriorated memory consolidation and executive functioning. These results add to the body of evidence supporting the utility of Macaca fascicularis in studies of cognition and as a potential translational model for age-associated memory impairment/dementia-related disorders.     

Genetic factors and a polygenic model of Alzheimer's disease

Genetic factors are responsible, to a certain degree, for many, if not all, Alzheimer's disease (AD) cases. A certain proportion of early-onset (below 65 years of age) AD cases follows an autosomal dominant mode of inheritance. Three genes were identified whose mutations account for 50-70% of early-onset monogenic AD cases in AD pedigrees. These are the genes of the amyloid precursor protein (APP) and two presenilins (PS I and PS II). The polymorphic variant of apolipoprotein E, APOE epsilon 4, is a genetic causative factor in familial and sporadic cases of various early- and late-onset AD forms (it is found, in general, in 20-50% of all AD cases). The action of the epsilon 4 allele is codominant, with the AD risk increased in homozygotes (epsilon 4/epsilon 4 > epsilon 4 > epsilon 3 or epsilon 2). In contrast to the mutations in the PS I and APP genes, the APOE epsilon 4 allele is not a necessary and sufficient condition for AD development. Mutations in these genes have not been found in a proportion of familial early-onset AD cases and are not causative factors in the majority of late-onset familial and sporadic forms. The genes determining AD are evolutionarily conservative and are expressed in all human tissues as early as at initial ontogenetic stages. This raises the question as to why AD is a progressive disorder affecting certain cerebral regions only at middle or old age. A hypothesis and model are suggested to explain the interaction between evolutionary, ontogenetic, and epigenetic factors of the development of the central nervous system and the products of genes whose mutations result in AD. Findings of different mutant genes indicate that AD is a set of genetic disorders (ADs) with a common pathological manifestation.     

Behavioral compensations in a positional learning and memory task by aged monkeys

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.     

Age-related alterations in the development of adrenergic denervation supersensitivity.

The density of beta-adrenergic receptors in the central nervous system exhibits marked age-related changes. In general, there is an initial increase in receptors soon after birth followed by a decline with advancing age; the specific pattern of the development and loss of receptors is dependent upon the brain area. The ontogenetic increase in the density of adrenergic receptors coincides temporally with the development of responsiveness to catecholamines but can proceed without an adrenergic innervation. This suggests that the biosynthesis of receptors is genetically predetermined and does not require an adrenergic input for initiation. Decreasing adrenergic activity produces an increased number of beta-receptors and a supersensitive response to adrenergic agonists. The decline in beta-receptors with advanced age appears to be related to this phenomenon of denervation supersensitivity since certain aged tissues have a diminished capacity to develop an increased number of receptors in response to a reduced sympathetic input. We conclude that the decline in beta-adrenergic receptors with age may explain the age-related decrease in the sensitivity of adenylate cyclase to catecholamines, and, consequently, the reduced physiological response to adrenergic stimuli. The mechanism for this loss of receptors may be the inability of aged tissue to develop a supersensitivity response in reaction to diminished sympathetic activity.