The effect of arginine vasopressin on the excitability and fatty acid content of the brain structures in rats with a neurosis

Experiments on rats with chronic bipolar electrodes implanted into the frontal cortex (FC), dorsal hippocampus (DH) and midbrain reticular formation (RF) established that the neurotic state (model "conflict of afferent excitation") was characterised by the increase in structure excitability: FC--15.4% (P less than 0.01), DH--12.4% (P = 0.05) and RF--17.5% (P less than 0.001). The presence of free fatty acids (FFA) revealed by chromatograph Schimadzu in brain cortex (BC), hippocampus (H) and midbrain (MB) in acute experiments evidenced the increase in the level of linolinic acid in all matters within the limits of 64-162% (P less than 0.05) and also different changes in arachidonic acid in BC and subcortical structures. The level of arachidonic acid increased by 120% (P less than 0.01) in BC but it decreased in H and MB within the limits of 34-56%. AVP (1 micrograms/kg) decreased excitability of FC by 6% (P less than 0.001), of H--by 8% (P less than 0.01) and RF--by 6%. In this case FFA, especially arachidonic acid, was increased in H and MB (by 2.5-6 times). The quantity of palmitic, stearic and oleic acids increased.     

Astrogliosis in the hippocampus and cortex and cognitive deficits in rats with streptozotocin-induced diabetes: Effects of melatonin

We examined, using a Western blot technique, the contents and compositions of a specific neuronal protein, NCAM, and of an astrocyte marker, GFAP, in the hippocampus and cortex of rats with streptozotocin (STZ)-induced diabetes and compared these indices with those in control (intact) animals and STZ-diabetic rats treated with melatonin. Behavioral cognitive indices manifested in the passive avoidance test (PAT) and Morris water maze (MWM) learning performance were also estimated in the above groups of animals. As was found, STZ-diabetic rats demonstrated clear cognitive deficits according to the values of the retention latency in the PAT and time of reaching the escape platform in the MWM performance. In these animals, the GFAP content was elevated, and the amount of degraded products of this protein increased, as compared with the control. Simultaneously, considerable down-regulation of the NCAM expression and modifications of NCAM isoform composition were found in diabetic animals. In addition, significantly increased levels of lipid peroxidation (according to the amounts of malondialdehyde + 4-hydroxyalkenals) were measured in the cortex and hippocampus of rats with stable diabetic hyperglycemia. All the above-mentioned shifts were significantly smoothed or even nearly completely compensated in the case of treatment of STZ-diabetic rats with melatonin (10 mg/kg per day). The role of diabetes-related changes in the amount and composition of specific neural and glial proteins in the development of cognitive deficits, the involvement of oxidative stress in the mechanisms of the respective shifts, and possible mechanisms of the neuroprotective effect of melatonin with respect to diabetes-related pathological biochemical and behavioral shifts are discussed. Neirofiziologiya/Neurophysiology, Vol. 40, No. 2, pp. 105–111, March–April, 2008.     

Effects of Ionizing Radiation and Aluminum Chloride on Protein of Glial Intermediate Filaments in the Rat Brain

We studied the effects of irradiation with X-rays (the total dose of 0.0129 C/kg was attained over 7, 14, or 21 days), increased entry of Al³⁺ into the organism (0.2% AlCl₃ in drinking water), and the combined influence of these factors for 21 days on the contents of the soluble and filamentous forms of glial fibrillary acidic protein (GFAP) in the tissues of the hippocampus, cerebellum, and neocortex of albino rats. After irradiation for 7 days, a clear trend toward drops in the GFAP contents in the structures under study was observed, while irradiation in the same dose, but for 14 or 21 days, resulted in increases in the contents of both GFAP forms (within a range of 13-29%, as compared with the control). Entry of aluminum chloride with water also resulted in an increase in the GFAP contents in all studied structures; changes in the filamentous form were more intensive. The combined influence of irradiation and Al³⁺ resulted in more intensive shifts in the GFAP levels; the content of its filamentous form increased in all structures by about 50%, while shifts of the soluble form were somewhat smaller.     

Role of Neuronal Cell Adhesion Molecules and N-Cadherin in Passive Avoidance Training of Rats

A comparative study of the role of specific adhesion proteins, NCAM (neuronal cell adhesion molecules) and N-cadherin, was carried out on rats subjected to passive avoidance training procedure. It was shown that antibodies against the Ca²⁺-dependent adhesion protein N-cadherin injected into the rat somatosensory cortical zone 6 h after passive avoidance training had been completed did not evoke a loss of the habit by experimental animals. At the same time, an absolute amnestic effect with respect to this reflex developed after injection of antibodies against NCAM. After injection of antibodies against the above-mentioned proteins into the dorsal part of the hippocampus, the avoidance habit also disappeared in the case of treatment with antibodies against NCAM and was kept under the influence of antibodies against N-cadherin. The data obtained testify that NCAM and N-cadherin play dissimilar roles in the formation of a memory trace in the course of training.     

Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus

Neurological and structural changes are paralleled by cognitive deficits in diabetes mellitus. The present study was designed to evaluate the expression of neural cell adhesion molecules (NCAM) in the hippocampus, cortex and cerebellum and to examine cognitive functions in diabetic rats. Diabetes was induced in male albino rats via intraperitoneal streptozotocin injection. Learning and memory behaviors were investigated using a passive avoidance test and a spatial version of the Morris water maze test. NCAM expression was detected in the hippocampus, cortex and cerebellum by an immunoblotting method. The diabetic rats developed significant impairment in learning and memory behaviours as indicated by deficits in passive avoidance and water maze tests as compared to control rats. Expression of NCAM 180 and 120 kDa were found to be higher in hippocampus and cortex of diabetic rat brains compared to those of control, whereas expression of NCAM 140 kDa decreased in these brain regions. Our findings suggest that streptozotocin-induced diabetes impairs cognitive functions and causes an imbalance in expression of NCAM in those brain regions involved in learning and memory. Altered expression of NCAM in hippocampus may be an important cause of learning and memory deficits that occur in diabetes mellitus.     

Characteristics of concanavalin A-binding neurospecific glycoproteins from various regions of the rat brain during experimental neurosis

The polypeptide composition of neurospecific glycoproteins in different areas of the rat brain under experimental neurosis is characterized using SDS-PAG-electrophoresis followed by electroblot and immunofixation on nitrocellulose membranes. The soluble and membrane-bound glycoproteins are purified by Con A-Sepharose column chromatography. Changes in the glycoprotein polypeptide composition in different areas of the rat brain under experimental neurosis are qualitative. Soluble glycopolypeptide 27 kDa and membrane glycopolypeptide 32 kDa are not revealed in the midbrain and corpus striatum. Soluble polypeptide 47 kDa is absent in the cerebral cortex and hippocampus. It is suggested that the above mentioned glycopolypeptides are important for the CNS physiological functioning.     

Effect of Vitamin E on the Content and Polypeptide Composition of Glial Fibrillary Acidic Protein from the Rat Brain under Conditions of Aluminum Chloride Intoxication

We studied the effects of isolated and combined chronic (21 days) introductions of aluminum chloride and vitamin E (α-tocopherol) on the polypeptide composition and content of glial fibrillary acidic protein (GFAP) in different brain structures of rats. Injections of AlCl₃ solution (12 mg/kg, i.p., daily) caused the appearance of low-molecular (47 to 38 kdalton) polypeptides and an increase in the content of GFAP in cytoskeletal fractions to 160 to 220%, as compared with the control. Introduction of vitamin E within the same interval provided significant normalization of the GFAP content in the brain of animals injected with AlCl₃ and to a considerable extent prevented the appearance of degraded polypeptides in the GFAP composition. We discuss the prospects of using vitamin E as an antioxidant for the correction of Al³⁺-induced pathological processes in the CNS.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 15–20, January–February, 2005.     

Melatonin is Involved in Regulation of the Expression of Neural Cell Adhesion Molecules in the Rat Brain

Cell adhesion molecules play a diverse role in neural development, signal transduction, structural linkage to extracellular and intracellular proteins, synaptic stabilization, neurogenesis, and learning. Neural cell adhesion molecules (NCAM) are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. There are three major NCAM isoforms: NCAM 180, NCAM 140, and NCAM 120. Several studies reported that NCAM play a central role in memory formation. We investigated the effects of melatonin on the expression of NCAM in the hippocampus, cortex, and cerebellum of rats. The levels of NCAM isoforms were determined by Western blotting. After administration of melatonin for 7 days, the expression of NCAM 180 increased both in the hippocampus and in the cortex, as compared with the control. In contrast, in rats exposed to constant illumination for 7 days (a procedure that inhibits endogenous production of melatonin), levels of NCAM 180 dropped in the hippocampus and became undetectable in the cortex and cerebellum. Levels of NCAM 140 in the hippocampus of light-exposed rats also decreased. There was no change in the expression of NCAM 120 in any brain region. This is the first report indicating that melatonin exerts a modulatory effect on the expression of NCAM in brain areas related to realization of cognitive functions. Melatonin may be involved in structural remodeling of synaptic connections during memory and learning processes.     

Evoked Activity of Afferent and Efferent Fibers of the Sciatic Nerve in Rats under Conditions of Experimental Hyperthyroidism

In Wistar albino rats with experimental hyperthyroidism (HTh) and control animals, we measured parameters of the responses evoked in peripheral segments of the ventral and dorsal roots (VR and DR, respectively) by stimulation of the sciatic nerve. We found that the chronaxia of the afferent fibers of the sciatic nerve in HTh animals is shorter, while the duration of the mass action potential (AP) in the DR is somewhat longer than in the control. Under conditions of HTh, the excitation threshold of the efferent fibers became higher, the chronaxia decreased, and the second high-amplitude component could appear in the AP recorded from the VR. Possible mechanisms of changes in the excitability of afferent and efferent fibers of the sciatic nerve and specific features of the AP recorded from the VR under HTh conditions are discussed. In particular, we consider the possibility of ephaptic spreading of excitation in VR fibers under HTh conditions.     

The protein of glial intermediate filaments in different areas of the rat brain at experimental neurosis

The content and polypeptide composition of glial fibrillary acidic protein (GFAP) in the rat cerebral cortex, cerebellum, hippocampus, and mesencephalon were studied under conditions of experimental neurosis. Significant changes of the total GFAP content were observed in the hippocampus, mesencephalon, and cerebellum. Both the content and polypeptide composition of soluble GFAP form were markedly modified. These changes of glial filament protein apparently reflect the peculiarities of the reorganization of the astrocyte intermediate filaments at the animal’s long-term neurotization.