Change in heat loss as a part of adaptation to repeated cold exposures in adult and aged male C57BL/6J mice.

Previous studies have shown that adult mice increase cold-induced heat production as a result of repeated exposures to cold, but that aged mice do not. The objective of the present study was to investigate changes in heat loss during repeated cold exposures in adult and aged C57BL/6J mice. Mice were partially restrained for three hours at 6 degrees C, three times at one-week intervals. Dry heat loss was inferred from measurements of differential temperature between the incoming and outgoing air in the experimental chamber. During the first cold exposure, aged mice showed less heat loss (both total and adjusted for body temperature) than adult animals, suggesting greater peripheral vasoconstriction in aged mice. With repeated cold exposures, both age groups showed increased heat loss, but the aged mice showed greater increase of heat loss, so that by the third cold stress test, no significant differences in heat loss between adult and aged mice were observed. The increase of heat loss after repeated cold exposures in aged mice might reflect a lesser peripheral vasoconstriction, serving to reduce the possibility of tissue necrosis in the cold.

The effect of exercise training in a cold environment on thermoregulation in adult and aged C57BL/6J mice.

We studied the effect of exercise training in cold environment (six weeks of daily, one-hour runs on a treadmill at ambient temperature of 6 +/- 1 degrees C at 60-65% of VO2max) on cold-induced metabolic heat production, heat loss, and cold tolerance in adult and aged C57BL/6J male mice. In adult mice, exercise training in cold environment resulted in greater cold-induced heat production and cold tolerance without changes in heat loss, similar to the effects of daily cold exposure without exercise. In aged mice, daily cold exposures did not affect cold tolerance and cold-induced heat production, but exercise training in the cold resulted in greater cold-induced heat production and cold tolerance. Heat loss in aged mice increased similarly after both repeated cold exposures and exercise training in the cold. Therefore, mechanisms of effect of exercise training on cold tolerance are different in adult and aged animals. Exercise training in cold environment does not affect cold-induced heat production and cold tolerance in adult mice, but improves them in aged animals.

The effect of exercise training in cold on shivering and nonshivering thermogenesis in adult and aged C57BL/6J mice.

To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and nonshivering thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6 degrees C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced nonshivering thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment.

Heat loss during cold exposure in adult and aged C57BL/6J mice.

Metabolic heat production (MHP), colonic temperature (Tco), and nonevaporative (dry) heat loss were measured in ADULT and AGED C57BL/6J male mice during cold exposure. Dry heat loss was assessed as a differential temperature (Td) between incoming and outgoing air through the chamber for indirect calorimetry. The average Td during cold exposure normalized to surface area for ADULT mice was significantly higher than that for the AGED animals (0.0618 +/- 0.0003 degree C/cm2 and 0.0553 +/- 0.0005 degree C/cm2, respectively). Linear regression analysis showed that at the same Tco AGED mice showed lower values of Td normalized to surface area, indicating that at the same body temperature they were losing less heat than ADULT animals. It was concluded that age-related decline in cold tolerance in mice is not due to a lack of ability to reduce heat loss during cold exposure. On the contrary, AGED animals had lower heat loss in comparison with ADULT. We suggest that augmentation of heat conservation mechanisms is an adaptive response to diminishing cold-induced heat production.

Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection.

OBJECTIVES: To define the incidence of congenital cytomegalovirus (CMV) infection in a defined population in Israel as diagnosed by urine polymerase chain reaction (PCR), and to assess the utility of this method for screening for congenital CMV infection. DESIGN: A convenient sample of urine specimens from asymptomatic newborns were subjected to CMV PCR. Positive results were validated by urine tube culture and by determination of serum CMV IgM antibodies. Maternal CMV IgG was determined in a representative sample of mothers. Newborns with positive urine specimens underwent full clinical evaluation. Epidemiological characteristics of the mothers were extracted from the medical records. SETTINGS: Two medical centres in Israel with different population characteristics. PATIENTS: A total of 2000 newborns (1000 in each medical centre). MAIN OUTCOME MEASURE: Presence of CMV DNA in the urine. RESULTS: Despite significant epidemiological differences between the populations in the two hospitals, the CMV seroprevalence was similar, 80.5% and 85%. Fourteen of the 2000 newborns screened (0.7%) were PCR positive. Urine culture was positive in nine of 10 specimens; IgM was positive in only two of 13 newborns with positive PCR. Eleven newborns underwent full or partial evaluation, and only one (9%) was symptomatic. CONCLUSIONS: The incidence of congenital CMV infection in the study population was 0.7%; over 90% were asymptomatic. Urinary CMV PCR is a reliable, rapid, and convenient method, and thus may serve as a screening tool for the detection of congenital CMV infection.

Neurophysiological mechanisms of cortical-subcortical interactions in the organization of behavior.

Experimental data are discussed within the framework of the fundamental areas of studies of the neurophysiological mechanisms of behavior. The first of these is the study of the activity of individual neurons, which is characterized by plastic rearrangements based on synaptic, molecular (neurochemical), and submolecular (genetic) processes. The second area is the study of the activity of neuron systems, which unite the cells of different microgroups, and of systems including neural elements of different brain structures. Data on plastic rearrangements of neuronal activity in different structures during different types of behavior lead to the conclusion that the brain has special systems of relationships which characterize the interactions of blocks of neurons, in which the plasticity of a single neuron can maintain the integration processes of the whole system. Our own data, along with results of Russian and foreign physiological and clinical investigations, suggest that neurons unite into different functional blocks at different phases of conditioned reflex behavior, thus determining the dominance status of different centers and the vector of a purposive behavioral act in a given situation at a given time. Possible directions for further basic studies of the interactions between innate and phylogenetically acquired functionally specific neuron units are discussed on the basis of hypotheses which have been advanced to explain the neurophysiological organizational mechanisms of higher brain functions.

The morphological basis of age-induced memory changes.

The results are presented of a layer-by-layer electron microscopic study of the cortex (40th area) in persons aged 78, 79, and 83 years whose anamneses did not include any neuropsychic disorders and who had died during surgical intervention These findings are examined in the light of current hypotheses about the morphological substrate of the mechanisms of memory. Cortical changes are uncovered which, according to these hypotheses, lie at the basis of the memory mechanisms. These include changes of the cytoplasm, neurocytes, dendrites, spines, axons, and their terminals. The same types of changes are found in the auditory cortex of old cats used for the control of the degree of preservation of elements of the human cortex.

Structure of neuronal activity of the caudate nucleus of monkeys during decision-making and the realization of the motor program in different variants of a delayed spatial choice task.

In this paper the results of investigations of the participation of caudate nucleus neurons in the decision-making process and the process of organization of the program of a future motor response during the performance by Macaca mulatta monkeys of a delayed spatial choice tasks of varying degrees of complexity are presented. The presence in the caudate nucleus of spatially selective neurons, which are subdivided into two groups, was established: the position of conditional signals is reflected in the activity of one of the groups, and the direction of the future motor response is reflected in the activity of the other. The decision-making process is reflected in the impulse activity of neurons of the head of the caudate nucleus in two of its aspects: as the formation or choice of a specific motor program (spatially selective activity) and as a transitional factor from the instructive to the executive phase of the behavior.

Corticostriatal mechanisms of behavior.

This article presents the results of three series of experiments on cats, dogs, and lower primates, performed to investigate the structural, neurophysiological, and mediator mechanisms of the corticostriatal systems involved in the organization of behavior. Morphological studies of corticostriatal connections showed that along with the diffuse distribution of afferent terminals within the striatum, there were also elements of topical organization defined by anteroposterior and mediolateral gradients. Neurophysiological experiments on dogs and lower primates were used to study the spike activity of the prefrontal region of the cortex and the head of the caudate nucleus during training to conditioned first- and second-order reflexes and during the solution of complex problems involving delayed spatial selection. Studies demonstrated that while in dogs, most of the neurons recorded showed a transition to responses to the conditioned signal at a particular stage of carrying out a conditioned response, in monkeys all cells recorded showed specific responses at different periods of solving the task at all stages of the study. Neuropharmacological experiments on dogs showed that agents blocking glutamine receptors in the caudate nucleus had more pronounced effects at the phase of developing conditioned movement reflexes. Administration of these agents during the reflex reinforcement phase affected only the differentiation of inhibition. These results lead to the conclusion that the prefrontal area of the cortex and, to some extent, the caudate nuclei, act on incoming information specifying the current dominant need and the states of the external and internal environments, to carry out programmed actions and assess the results of these actions.

[The neuronal activity of the caudate nucleus in monkeys during the realization of delayed behavior]. / Neironnaia aktivnost' khvostatogo iadra obez'ian pri realizatsii otsrochennogo povedeniia.

A greater part (64%) of recorded neurones of the caudate nucleus head changed its activity at various stages of fulfillment by the monkey of the task of delayed spatial choice. Most of them (46.5% of all studied) reacted at key depressing and/or taking food from the feeder. During signal presentation and with delay the frequency of impulse activity changed respectively in 17% and 14% of the studied neurones. Besides, 2 neurones had spatially-selective activity in the instructive period of the program. It can be suggested that caudate neurones participate in realization of the delayed behaviour not only during motor response fulfillment but in the instructive period as well--at the stage of perception and processing of the visual information and its storing in short-term memory.

[Characteristics of the activity of neurons of the parietal cortex of alert monkeys in comparison to the frontal and motor areas]. / Kharakteristika aktivnosti neironov temennoi kory bodrstvuiushchikh obez'ian v sravnenii s lobnymi i motornymi oblastiami.

Analysis was made of spike activity of nerve cells in the parietal cortex of alert Macaca mulatta when the animal performed the task of delayed alternative choice. The parietal cortex neurones (at the boundary between fields 5 and 7) were divided into two groups by the mean background frequency of their spike activity and by their functional properties. Cells with relatively low frequency (up to 10 imp/s) resemble by their functional properties prefrontal cortex neurones, whereas neurones with a background frequency over 10 imp/s reveal a similarity with motor cortex cells.

[Responses of neurons of the motor and frontal cortex of monkeys during performance of purposeful activity]. / Reaktsii neironov motornoi lobnoi oblastei kory mozga obez'ian pri vypolnenii tselenapravlennogo dvizheniia.

Neurones of the frontal cortex in alert monkey reveal most diverse rearrangements of spike activity at the programming stage of a behavioural task. Their responses depend on 1) position of the conditioned signal, 2) direction of the forthcoming movement toward reinforcement (feeding trough), and 3) efficiency of performing the goal-directed movement, which, if correct, is reinforced with food. Units in the motor cortex have higher background activity, they are most active during triggering stage and their activity does not reflect signal position and estimation of success (by reinforcement). The suggestion is made on the role of the frontal cortex in programming of movements and estimation of their efficiency, as well as on the role of the motor cortex in their coordinated achievement involving somatic processing of the connection.

[Hypo- and hyperdiagnosis of senile dementia and Alzheimer's disease in psychiatric practice]. / Gipo- i giperdiagnostika starcheskogo slaboumiia i bolezni Al'tsgeimera v psikhiatricheskoi praktike.

A total of 714 brains from patients of predominantly advanced age who died in mental (n = 546) and somatic (n = 168) institutions have been examined macro- and microscopically. It has been found on the basis of accurate postmortem verification of Alzheimer's disease (AD) and senile dementia (SD) that in 20% of cases psychiatrists erroneously diagnose feeblemindedness in old age and in about the same proportion of cases they fail to diagnose the actual disease (most often AD and SD). The author has revealed a marked hyperdiagnosis of hypophrenias of vascular genesis at the expense of AD and SD whose rates are obviously underreported and which play a greater role in gerontopsychiatric practice than is generally accepted.

[Relation between the degree of severity of the dementia and the extent of the manifestation of the pathomorphological changes in the cerebral cortex in senile dementia and Alzheimer's disease]. / Sviaz' mezhdu stepen'iu tiazhesti dementsii i vyrazhennost'iu patomorfologicheskikh izmenenii v kore golovnogo mozga pri starcheskom slaboumii i bolezni Al'tsgeimera.

A study of 169 patients with senile dementia and Alzheimer's disease included history collection and the examination of the temporal pole. In the preparations impregnated according to Bilshovsky (in strictly the same volume of the cortex), senile plaques, neurofibrillar nodes and neurofibrillar skeletons were counted. Subsequently, the degree of the pathomorphological changes in each case was scored. The collation of the anamnestic and pathomorphological findings demonstrated a marked correlation (r = 0.99 +/- 0.0015) between the severity of dementia and the degree of pathomorphological changes in the cortex of the temporal pole.

[Muli-infarct dementia]. / Mul'tiinfarktnaia dementsiia.

Two hundred and fifty-five cases of dementia of advanced age were studied. In 142 of them (56%) the clinical diagnosis was vascular dementia. In 55 the anatomical diagnosis was senile dementia or Alzheimer's disease and in only 40 cases with established multiple infarcts (in 38 cases they were localized in the area of the subcortical ganglia) the diagnosis was multiinfarction dementia. In 11 of these 40 cases, multiinfarction dementia was combined with senile dementia and Alzheimer's disease. In relation to all 255 studied dementias of advanced age multiinfarction dementia constituted 11% in its pure form and 18% in its mixed form.

[Pathologo-anatomic morphometric diagnosis of senile dementia and Alzheimer's disease]. / Patologoanatomicheskaia morfometricheskaia diagnostika starcheskogo slaboumiia i bolezni Al'tsgeimera.

The numbers of senile plaques, neurofibrillar bundles, and neurofibrillar "skeletons" in a certain constant volume of the left temporal pole cortex were calculated in 131 psychically healthy subjects who died at an age of 41 to 101 years, and in 111 subjects who suffered at lifetime from debilitating diseases of the type of senile dementia (dotage) and Alzheimer's disease. Each senile plaque was estimated at 0.1 point, and each neurofibrillar bundle and neurofibrillar "skeleton" at 1.0 point. In each case the points were summed up. In 86% of the cases of senile dementia and Alzheimer's disease the total of the points exceeded the maxima found in the psychically healthy subjects. This gives one grounds to recommend this method for making reliable pathoanatomic diagnoses of debilitating diseases of the type of senile dementia or Alzheimer's disease.

[Hippocampal pathology as one of the possible factors in the pathogenesis of several dementias of old age]. / Patologiia gippokampa kak odin iz vozmozhnykh faktorov v patogeneze nekotorykh dementsii pozdnego vozrasta

In the light of comtemporary concepts concerning the functional significance of the limbic system, the author reports of some results in the subiculum in young and old individuals (39 cases) with different forms of dementia of old age (senile and vascular dementia, Pick's and Alzheimer's disease). The authors assessed the thickness of the subicular cortical stratum, the relative and absolute amount of nervous and glial cells and capillaries. In old age the thickness of the subicular cortical stratum is decreased by 28%, while the absolute amount of neurons by 29%. In old age dementia the thickness of the subicular cortical stratum decreased by 47--71% and the absolute amount of neurons becomes 2--3 times less. In old age in general and in dementia of old age in particular there was no "substitutional" gliosis because the absolute amount of glial cells in the cortical stratum is reduced in this group of individuals by 20--50%.

[Changes in the cerebral cortex in temporal lobe epilepsy]. / Izmeneniia v kore golovnogo mozga pri visochnoi épilepsii.

Biopsy specimens of the temporal cortex were taken from three patients suffering from temporal epilepsy of different origin. As a result of examining the specimens under optic and electron microscopes and subsequent morphometric processing of the data a picture of layer-by-layer changes in the cortex (field 21/38) was obtained. These changes consisted in appearance of the so-called dark cells, degenerating synaptic buds and myelin fibres, and increase of the percentage of astrocytes and proliferation of their processes. The data obtained suggest that in this disease there occurs a gradual destruction of neurocytes which leads to disturbances of the interneuronal relations.

[Pathogenesis and pathomorphology of human leukodystrophies]. / Patogenez i patomorfologiia leikodistrofii cheloveka.

A review of foreign literature on the pathogenesis and pathomorphology of hereditary diseases of the human nervous system with the myelin involvement is presented. Five forms of leukodystrophies are mainly dealt with: (1) metachromatic, with the defect of their deposition in the form of a metachromatic substance; (2) globoid, with deficiency of galactoceramide beta-galactase enzyme catabolizing cerebrozides and with accumulation of the latter, particularly in the forming "globoid" cells; (3) sudanophilic, with sudanophilic degeneration of the myelin and obscure defect of the enzyme; (4) Pelizaeus-Merzbacher disease with insularly intact myelin; and (5) adrenoleukodystrophy with sudanophilic degeneration of the myelin and involvement of the adrenals. All the forms of leukodystrophies by the time of the onset of the disease are divided into prenatal, late infantile, juvenile, and adult.

[Hereditary demyelination in mutant quaking mice (breeding and light microscopy)]. / Nasledstvennaia dismielinizatsiia u mutantnykh myshei kvoking (razvedenie i svetovaia mikroskopiia).

Data on breeding of mutant Quaking mice (MQM) and the results of light microscopy and morphometric examination of the central and peripheral nervous systems in them and in control mice varying in ages from 12 days to 4 months are presented. MQM were shown to have a decreased total volume of the white matter due to underdevelopment of myelin because of disturbed function of myelin-forming cells (oligodendrocytes). At the same time oligodendrocytes retain their capacity for proliferation and are normally located interfascicularly in the white matter having the same density of occurrence and the same average volume of the nucleus as in controls, but morphologically they are similar to oligodendroblasts. Another morphological feature of MQM consists of intensive vacuolation of their gray and white matter. However, light microscopy could not determine whether the vacuoles 1 to 9 microns in diameter were located intra- or extracellularly. No pathological changes in neurocytes, astrocytes or capillaries were observed.