[Effects of repeated short-term immobilization stress on plastisity of brain cortical division and cognition in adult rats with normal and disturbed embryogenesis].

The aim of the work was the analysis of the changes in a number of labile synaptopodin-positi- ve dendritic spines in parietal cortex and the CA1 field of the hippocampus, which characterize plasticity of intracellular interaction, and of the memorization after short-term repeated immobili- zation stress (daily for 5 minutes, 10 days), both in control rats and in rats subjected to prenatal hypoxia (E14, 7% of O2, 3 hours). There were observed deterioration of short-term and long-term memory, decrease in number labile spines in the CA1 field of the hippocampus (for 17.3 ± 10.4%; p ≤ 0.05) and their increase in a molecular layer of brain parietal cortex (for 36.9 ± 9.2%) at the adult rats with normal embryogenesis after immobilization stress in comparison with control intact animals. At the rats subjected to a prenatal hypoxia, regardless of that, they were ex- posed to an immobilized stress at an adult stage or not, was noted both violation of short-term and long-term memory, and decrease in number labile spines in the CA1 field of the hippocampus (for 22.9 ± 10.5%) and parietal cortex (for 28.1 ± 9.3%). The obtained data allow to conclude that the increase of plasticity providing adaptive behavior of animals, takes place in neocortical neuronal networks as a reply to a short-term repeating stress only at normal brain formation during embryo- genesis, while, violation of embryogenesis leads to decrease in plasticity and adaptive opportuni- ties of the nervous system during further ontogenesis.

[Changes in the activity of amyloid-degrading metallopeptidases leads to disruption of memory in rats].

In old male Wistar rats (older than 12 months), or adult males (3-4 months) subjected to prenatal hypoxia (7% 02, 3 h, E14), a disruption of short-term memory was observed. The prenatal hypoxia also led to a decrease in the brain cortex expression of metallopeptidases neprilysin (NEP) and endothelin-converting enzyme (ECE-1) which regulate some neuropeptides and are the main beta-amyloid-degrading enzymes. Moreover, a significant decrease (by 2.7 times) in NEP activity in the sensorimotor cortex of old and adult rats subjected to prenatal hypoxia (by 1.7 times) was observed. To confirm possible involvement of these enzymes in memory, the analysis of the effect of microinjections of phosphoramidon (an inhibitor of NEP and ECE-1), and thiorphan (an inhibitor of NEP) into the rat sensorimotor cortex was carried out. In a two-level radial maze test, a disruption of short-term memory was observed 60 and 120 min after i.c. injection ofphosphoramidon (5.9 microg/microl) and 30 and 60 min after i.c. injection of thiorphan (2.5 microg/microl). The involvement of NEP and ECE-1 in short-term memory suggests that a decrease in the level of expression and activity of metallopeptidases involved in metabolism of beta-amyloid peptide (Abeta) and other neuropeptides is one of the main factors in disruption of cognitive functions after prenatal hypoxia or in the process of ageing.

[Specificity of ontogenic development of behavior of rats subjected to prenatal hypoxia on the 14-th or 18-th days of embryogenesis].

Physiological development, movement activity and cognitive functions of rats subjected to acute normobaric hypoxia (7% O2 during 3 h) at different days of embryogenesis (E14 or E18) were investigated. It was found that prenatal hypoxia led to a delay in physiological development and formation of motor behavior during the 1st month after birth. Differences observed were more pronounced in rats subjected to hypoxia on the 14th day of intrauterine development but disappeared with maturation of the animals. Independently of the day of the hypoxic episode (E14 or E18), learning ability and memory (long-term and short-term) impaired in all adult rats. The findings suggest that the exposure to hypoxia at the stage of predominant generation and migration of neuroblasts (E14) is disruptive for physiological development, formation of motor behavior and cognitive function, whereas the exposure to hypoxia at the stage of predominant cell maturation (E18) is in general more disruptive for cognitive functions.

[Formation of structural and ultrastructural organization of striatum rat postnatal ontogenesis upon changes in their embryonal development].

By light microscopy (by Nissl and Golgi), electron microscopy, and immunohistochemistry methods, formation of structure of the brain striatum dorsolateral part from birth to the 3-month age was studied in rats submitted to acute hypoxia at the period of embryogenesis. It has been established that hypoxia at the 13.5th day (E13.5) leads to a delay of neuronogenesis for the first two weeks of postnatal development as compared with control animals, while the majority of large neurons at this period are degenerated by the type of chromatolysis with swelling cell body and processes and lysis of cytoplasmic organoids. By the end of the 3rd week, shrunk hyperchromic or picnomorphic neurons with the electron-dense cytoplasm and enlarged tubules of endoplasmic reticulum and Golgi complex were also observed. An increased number of swollen processes of glial cells was detected in neuropil around degenerating neurons. By the 30th day as well as in adult rats there was observed destruction of mitochondrial apparatus, an increase of the number of lysosomes, and the appearance of bladed nuclei - signs of apoptotic cell death, which was also confirmed by an increased expression of proapoptotic p53 protein and its colocalization with caspase-3 in a part of neurons. Morphometrical analysis has shown a decrease of density of striatum cell arrangement and a change of ratio of different cell types in the rats submitted to hypoxia as compared with control group. At early stages of postnatal ontogenesis there was the greatest decrease (42.3% at the 5th day, 14.2% at the 10th day, p < 0.01) of the number of large neurons with the area more than 80 microm2. After 3 weeks of postnatal development the number of middlesize neurons (30-95 microm2) decreased (by 11.8-19.2%) as compared with control. The obtained data show that a change of conditions of embryogenesis (hypoxia) at the period of the most intensive proliferation of the forebrain neuroblasts leads to disturbances of the process of formation of the striatum nervous tissue. This can be the cause of delay of development and disturbances of behavior and learning observed in rats submitted to prenatal hypoxia.

[Formation of striatum structural and ultrastructural organization in the early postnatal ontogenesis of rats subjected to altered conditions of their embryonic development].

Formation of the structure of striatum during two postnatal weeks in rats subjected to acute hypoxia during various periods of their embryonic development was studied using light microscopic (Nissl's stain and Golgi's silver nitrate impregnation) methods and electron microscopy. This study was supplemented by a simultaneous investigation of physiological development of the same population of rats. The data obtained demonstrated that prenatal hypoxia on day 13.5 of embryonic development (E13.5) led to a delayed neurogenesis (retardation in the development of neuropil elements and cell differentiation) as well as to the malformation of the structure of striatum (degeneration, in particular, chromatolysis of neurons and glial nodule formation). Morphometric analysis demonstrated that prenatal hypoxia on E13.5 resulted in a statistically significant decrease in cell number in the striatum, these changes being especially pronounced in large neurons. Prenatal hypoxia on E18.5, however, caused no significant changes in striatum. Structural changes in the striatum were shown to be accompanied by significant changes in the physiological development of animals. The data obtained demonstrated that the alteration of the conditions of embryogenesis (hypoxia) during the period of most intensive proliferation of forebrain neuroblasts resulted in the disturbances of the formation of both striatum nervous tissue of the organism as a whole during early postnatal ontogenesis.

[Effect of an inhibitor of alpha-secretase metabolizing amyloid precursor protein on memory in rats].

Intracortical administration of 10(-4) M batimastat, a specific inhibitor of one of metalloproteinases metabolizing amyloid precursor protein, namely alpha-secretase, to adult rats resulted in a decrease in the number of correct runs in a one-level 8-arm maze down to 92.78 +/- 1.03% of the control values (p < 0.01) already 60 min after an injection. The effect of a single injection of the inhibitor to adult rats did not have a prolonged character. However, injections of batimastat into the cortex of brain hemispheres of rats during early postnatal ontogenesis (5th and 7th days after birth) resulted in considerable deterioration of 8-arm maze orientation of these animals at adult age (90.92 +/- 2.21% of correct runs, p < 0.001) compared to control animals. The findings suggest an important role of alpha-secretase in memorization. A possible role of alpha-secretase in memory and pathogenesis of Alzheimer's disease is discussed.

[Postnatal physiological development of rats after acute prenatal hypoxia]. / Postnatal'noe fiziologicheskoe razvitie krys posle ostroi prenata'noi gipoksii.

The aim of study was to investigate the physiological development of the brain and behaviour in rats subjected to prenatal hypoxia on the 13.5th day of embryogenesis. We have found that such rats manifested a delayed physiological development and a change in nervous tissue of the sensorimotor cortex, as well a disturbed formation of motor responses during the first month of postnatal ontogenesis. During maturation these modifications were in part compensated, however we observed a decrease of the rats' ability to learn new forepaw movements. The destruction of the brain tissue and the modification of neurons composition in the sensorimotor cortex correlated with changes of behaviour at different stages of ontogenesis. Thus, changes of the conditions under which an organism develops during embryogenesis, predetermine a disturbance in ontogenesis and the learning ability.

[The participation of the cholinergic system of the rat sensorimotor cortex in regulating different types of movements]. / Uchastie kholinergicheskoi sistemy sensomotornoi kory mozga krysy v reguliatsii raznykh tipov dvizhenii.

To study the role of the cholinergic system of the sensorimotor cortex in regulation of different manipulatory movements and locomotion of Wistar rats, the effects of injections of cholinergic drugs (a cholinergic agonist carbachol and an antagonist scopolamine) into the area of forepaw representation in the sensorimotor cortex on motor activity and performance of manipulatory movements (with prolonged and short pushing) were analyzed. The drugs were injected via special cannulae stereotaxically implanted into the cortex during surgery carried out under Nembutal anesthesia. Carbachol injections (0.03-3 micrograms in 1 microliter of physiologic solution) into the cortex resulted in a significant slowing down of both types of movements as well as an increase in locomotion in the open-field test. Injections of scopolamine (0.3-3 micrograms) into the same cortical area were accompanied by an increase in the number of fast manipulatory movements without significant changes in locomotor activity. The obtained evidence suggests that the cholinergic system of the sensorimotor cortex indifferent manners regulates the innate (locomotion) and acquired movements which require different periods of maintaining the muscle tone of the forepaw (short-time periods for the usual movements necessary for food taking from the narrow horizontal tube and prolonged periods for the learned slow movements with additional tactile and tonic components).

[Role of the cholinergic system in the dorsal and ventral striatum of the brain in regulation of a learned movement in rats]. / Rol' cholinergicheskikh sistem dorsal'nogo i ventral'nogo striatuma mozga krysy v reguliatsii vyuchennogo dvizheniia.

Administration of carbachol into the rat brain ventral striatum increased the number of movements with prolonged extension and decreased the number of short not reinforced movements, whereas the same administration into the dorsal striatum deteriorated slow movements. Scopolamine administration, irrespective of the site, increased the number of fast not reinforced movements. The findings suggest that cholinergic system of the rat ventral striatum is involved in the maintenance of the rat forepaw muscle tone.

[Adenylate cyclase and 5'-nucleotidase activities in the sensorimotor and limbic structures of the rat brain after training in a manipulative skill]. / Aktivnost' adenilattsiklazy i 5'-nukleotiday v sensomotornykh i limbicheskikh strukturakh mozga krys posle obucheniia manipuliatornomu navyku.

The activities of adenylate cyclase (AC) and 5'-nucleotidase (NT) were studied in the limbic (amygdala, hippocampus) and sensorimotor (cortex, striatum) brain structures of three rat groups: control (without training), not well and well learning to perform movements with pushing the operandum. It was found, that after training the activity of AC was decreased in all structures studied. Moreover, in the cortex and the striatum the decrease was more pronounced in the group of well learning rats, while in the amygdala--in not well learning ones. The activity of NT in all brain structures, excepting the striatum, was more significantly decreased in the rats with low ability to learn the movements with prolonged pushing. Only in the striatum the increase of NT activity (initially the lowest in the control animals--1.0 +/- 0.04 microgram P(i)/mg protein/min) up to 1.3 +/- 0.1 in not well and up to 2.0 +/- 0.1 in well learning animals was found. The interhemispheric [correction of intrahemispheric] asymmetry of AC activity in the cortex and of NT in the hippocampus was revealed. Thus, the changes of the activity of the enzymes, participating in the biogenesis of adenosine (NT) and c-AMP (AC) are different in the limbic and sensorimotor structures dependently on learning ability of rats. The increase of NT activity after learning only in the striatum could reflect a specific role of purinergic system of this brain structure in the regulation of sensory controlled movements.

[The sensory and motor components of different forms of learned movement during a change in the activity of the neostriatal cholinergic system]. / Sensornye i motornye komponenty raznykh form vyuchennogo dvizheniia pri izmenenii aktivnosti kholinergicheskoi sistemy neostriatuma.

The role of the neostriatal cholinergic system in the regulation of sensory controlled movements were studied using two behavioral models: 1) maintenance acquired extension of forelimb during proper time (rats) and 2) prolonged conditional flexion of hindlimb (dogs). It was found that injections of carbacholine (Car, 0.03 mkg) into the dorsolateral part of nucleus caudatus (NCd) of rats did not considerable change the movement connected with maintenance of forelimb tonus, while injections of Car (0.05-0.1 mkg) into the same area of the NCd of dogs were accompanied by improved performance of movement connected with maintenance of hindlimb tonus. It is possible to suggest the follows: 1. The neostriatal mechanisms of regulation of fore- and hindlimb tonus maintenance are different. 2. The neostriatal mediator of mechanisms of tonus regulation and regulation of somesthetic control of maintenance of this tonus are probably different too. Bilateral Car microinjections (0.03 mkg) into NCd of rats improved the discriminative active avoidance learning in T-maze. The discrimination of sound signals in dogs were also significantly improved after Car injections (0.05-0.1 mkg) into the NCd. Thus, data obtained at the different behavioral models and different animals suggest that cholinergic system of Neostriatum takes part in the regulation of both motor and sensory components of learned movements realization. The possible mechanisms of this regulation are discussed.

[The neurochemical characteristics of the rat neostriatum and motor cortex after the acquisition of a unilateral manipulatory reflex]. / Neirokhimicheskie kharakteristiki neostriatuma i motornoi kory krysy posle vyrabotki odnostoronnego manipuliarnogo refleksa.

The activity of acetylcholinesterase (AChE), 5'-nucleotidase (NT) and adenylate cyclase (AC) were studied in sensomotor cortex and neostriatum (NS) from right and left hemispheres of control and experimental rats, trained to perform food reaching with pushing on operant by preferable forepaw. The levels of summarized bilateral activity of NT as well as of AC were found to be similar in both studied structures of control rats, while the activity of AChE was higher in NS than in cortex. In trained rats the activity of AC was decreased both in cortex and NS, the activity of NT was decreased in cortex and increased in NS, AChE being not changed when compared with control. The bilateral values of enzyme activities in well and badly learning rats were significantly different. Meanwhile, when the dominant and subdominant hemispheres were compared these values were found to be similar. In general, the results obtained could be evaluated as specific features of conditioned unilateral manipulatory reactions, characteristic for cortex and NS of brain hemispheres.

[The effect of exogenous gangliosides on the formation in rats of instrumental movements with tactile control]. / Vliianie ékzogennykh gangliozidov na formirovanie u krys instrumental'nykh dvizhenii s taktil'nym kontrolem.

The process of learning and memorization of instrumental reaching movements with pressure on an operandum by a preferable forepaw were studied in white rats after ganglioside injections. The coursed of learning in control and ganglioside injected animals were shown to be alike while some ganglioside treated rats demonstrated increased motor activity. After a 5-week interval animals of both groups were able to perform quick reaching movements, but the storage of ability to push the operandum during the defined time was revealed only in ganglioside injected group. It may be considered that the ganglioside injections support the long-term storage of learned movements with tactile control.