Effects of chronic stress and corticosterone on sialidase activity in the rat hippocampus.

Sialidases are acid exoglycosidases that catalyse the removal of sialic acid from non-reducing end of sialoglucoconjugated substrates. Synaptic plasticity depends on sialylation state of proteins and lipids mediated by sialic acid-metabolizing enzymes. Since chronic stress causes both, hippocampal atrophy and impairment of learning, it is reasonable to investigate whether sialidase is implicated in these processes. In this study, we tested effects of chronic stress (immobilization, 2h daily, 21 days) or chronic corticosterone administration (5 mg/kg, sc, daily) on sialidase activity and sialylated NCAMs expression in rat hippocampus. The results showed that chronic stress affects hippocampus-depended spatial learning in the Barnes maze. Both, stress (p > 0.05) and corticosterone (p < 0.001), increased latencies to enter the escape tunnel of the maze in comparison to control animals. Similar but not significant differences between control and other experimental groups were observed in the numbers of errors. Chronic stress (p > 0.05) and corticosterone (p < 0.05) decreased sialidase activity in the brain homogenates and synaptosomes (p < 0.05, both). In the stressed animals, these changes were related to significantly higher expression of polysialic acid. These results indicate that changes in sialidase activity caused by stress and chronic corticosterone administration reflect disturbances of polysialylated glycoconjugates known to be related to synaptic plasticity in hippocampus.

Pro-cognitive effects of Cirsium rivulare extracts in rats.

AIM OF THE STUDY: Cirsium rivulare (Jacq.) All. (Asteraceae) is a herbaceous perennial plant occurring in Central Europe. It has been traditionally used in Polish folk medicine to treat anxiety. In the present study methanolic extracts from flowers and leaves of Cirsium rivulare containing flavonoid compounds linarin, pectolinarin, apigenin, hispidulin, their glycosides and a newly isolated compound isokaemferide 7-O-(6''-methylglucuronide) were studied for anxiolytic and pro-cognitive properties. MATERIALS AND METHODS: Male Wistar rats (150-160 g) were used. They were treated orally with standardized methanol extracts of flowers and leaves of Cirsium rivulare and subsequently tested for memory in passive avoidance (PA) and object recognition (OR) tests. Auxiliary tests for motor (open field, OF) and emotional (elevated 'plus' maze, EPM) effects of the above treatments were also employed. RESULTS: We found that the extract from flowers of Cirsium rivulare, in addition to its anxiolytic effects as measured in the EPM, improves memory of the appetitively (by curiosity, OR) and aversively (by footshook, PA) motivated tasks. This is in contrast to classical anxiolytics as for example benzodiazepines that typically impair memory. The extract from leaves of Cirsium rivulare showed some anxiolytic properties in the EPM, and no effect in both cognitive tests. The examined extracts of Cirsium rivulare did not affect psychomotor exploratory activity of rats tested in the OF. CONCLUSIONS: These results suggest that the flavonoids from Cirsium rivulare possess anxiolytic and pro-cognitive effects, the extract from flowers being more pro-cognitive and that from the leaves more anxiolytic.

Gingkoselect alleviates chronic corticosterone-induced spatial memory deficits in rats.

The preventive effects of Gingkoselect (100 mg/kg/day, orally, 21 days) on spatial memory deficits induced by a chronic restraint stress (2 h daily, 21 days) or chronic corticosterone treatment (5 mg/kg, subcutaneously, 21 days) were investigated using the Barnes maze. Chronic corticosterone, but not chronic stress, impaired spatial memory, as shown by increased latency to finding escape tunnel in the maze. Gingkoselect normalized cognitive deficits in rats chronically treated with corticosterone, and improved memory above the control levels in the chronically stressed rats.

WITHDRAWN: EGB 761 alleviates chronic corticosterone-induced spatial memory deficits in rats.

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Preventive action of Ginkgo biloba in stress- and corticosterone-induced impairment of spatial memory in rats.

In this study, we tested preventive effects of a natural medicine the extract of Ginkgo biloba (EGB 761) on post-stress cognitive dysfunction. Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and have been linked to the pathophysiology of mood and anxiety disorders. Our findings indicate that chronic restraint stress impaired egocentric spatial memory as observed in the eight-arm radial maze but it did not alter the allocentric spatial memory in the Morris water maze. In control rats EGB 761 (100mg/kg, orally) improved spatial memory in these two tests. Also, EGB 761 normalized cognitive deficits seen in rats chronically stressed or treated with an 'equivalent' dose of exogenous corticosterone (5mg/kg, subcutaneously). We conclude that, in rats, repeated administration of EGB 761 prevents stress- and corticosterone-induced impairments of spatial memory.

Effect of D(3) dopamine receptors blockade on the cognitive effects of angiotensin IV in rats.

Our previous studies showed that D(1) and D(2) dopamine receptors are indispensable for the cognitive effects of angiotensin IV (Ang IV) and its des-Phe(6) derivative des-Phe(6)-Ang IV to occur. As most neuroleptics currently used in the treatment of schizophrenia have variable D(2)/D(3) dopaminolytic selectivity, in this study we searched for the role of the D(3) dopamine receptors in facilitating learning and improving memory actions of Ang IV and des-Phe(6)-Ang IV in rats. For this purpose, we evaluated the recall of the passive avoidance (PA) behaviour, object recognition (OR) memory, and the spatial working memory (WM) in rats treated with the intraperitoneal (i.p.) nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide), a highly selective D(3) receptor blocker and then by an intracerebroventricular (i.c.v.) Ang IV or des-Phe(6)-Ang IV. Separate groups of rats receiving the same treatments were run to check for the possible participation of unspecific motor (open field) or emotioned (elevated "plus" maze) effects of our treatments in the results of the cognitive tests. The results revealed Ang IV to express its improving recall of PA, OR memory and WM action roughly similarly in all groups showing only minor or null significance of the D(3) receptors blockade. Interestingly, in the nafadotride pretreated rats, des-Phe(6)-Ang IV beneficial effect on the recall of the PA was weaker than that of Ang IV. Improvement of the spatial WM in an eight-arm radial maze, similar after Ang IV and des-Phe(6)-Ang IV, was not significantly affected by nafadotride. There were no motor and only minor anxiogenic effects of Ang IV and des-Phe(6)-Ang IV abolished by nafadotride in the former case. In conclusion, this study points to the minor significance of the D(3) dopamine receptors in the cognitive effects of Ang IV and to the interesting, though unexplained, inhibition by nafadotride of the des-Phe(6)-Ang IV effects.

Cognitive effects attributed to angiotensin II may result from its conversion to angiotensin IV.

This study tests the hypothesis that the facilitation of learning and improvement of memory observed after an intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) is, in fact, caused by its derivative angiotensin IV (Ang IV). We ran two memory tests as well as an auxiliary test assessing motor performance in rats injected (i.c.v., 1 nmol in 2 microl saline) with Ang II or Ang IV. There were separate groups receiving peptide or saline five, 10 and 15 minutes before testing. Ang IV significantly increased step-through latencies in a passive avoidance paradigm as well as improved discrimination between familiar and unfamiliar objects in an object recognition test in all groups showing better retrieval of memory of aversive as well as appetitive stimuli in the peptide-treated groups regardless of the time of its injection. In contrast, rats treated with Ang II demonstrated significant improvement of memory of aversive and appetitive stimuli in the same tests only 15 minutes after its i.c.v. injection, with no effect in the groups injected five minutes before testing and slight efficacy in those injected 10 minutes before the test. Numbers of crossings, rearings and bar approaches in an open field were similar both in the peptide-treated and control groups making it unlikely that changes in motor performance affected the memory tests. In line with the present views on the intracellular metabolism of Ang II, these results suggest degradation to Ang IV by aminopeptidases A and N is necessary before the cognitive effects can occur.

St john's wort (Hypericum perforatum) counteracts deleterious effects of the chronic restraint stress on recall in rats.

This study aimed at verifying a hypothesis that St. John's wort (Hypericum perforatum) alleviates stress-induced memory impairments. Administration of Hypericum perforatum (350 mg kg(-1) daily for 21 days) significantly enhanced recall of passive avoidance behavior (PAB), but had no effect on the acquisition of conditioned avoidance responses (CARs). Rats stressed chronically (2 h daily for 21 days) displayed diminished recall of the PAB and this effect was abolished by St John's wort. Chronic administration of the "equivalent" to the stress dose of exogenous corticosterone (5 mg kg(-1) daily for 21 days) also impaired recall of PAB, and this effect was also reversed by Hypericum perforatum. None of our treatments produced significant motor coordination impairments as tested in a 'chimney' test. It appears that H. perforatum prevents stress-induced deterioration of memory in rats.

Ginkgo biloba normalizes stress- and corticosterone-induced impairment of recall in rats.

Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and has been linked to the pathophysiology of mood and anxiety disorders. Antianxiety or sedative agents used in the management of stress have several disadvantages and side effects. Therefore, in this study, we investigated efficacy of a natural medicine, the extract of Ginkgo biloba (EGB 761), in prevention and treatment of the post-stress memory dysfunctions. The results showed that chronic restraint stress (2h for 21 days) or an 'equivalent' dose of exogenous corticosterone (5 mg kg(-1)) decreased re-entry latencies in the passive avoidance situation showing thus impairment of recall. Preventive doses of EGB 761 (100 mg kg(-1)), given 30 min before each restraint stress episode or corticosterone injection, abolished cognitive deficits seen in unprotected rats. There was no influence of stress, corticosterone, and EGB 761 on the acquisition of conditioned avoidance responses (CARs).

Gingko biloba extract diminishes stress-induced memory deficits in rats.

Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and has been linked to the pathophysiology of mood and anxiety disorders. Antianxiety or sedative agents used in the management of stress have several disadvantages and undesired effects. Therefore, in this study, we investigated efficacy of a natural medicine, the extract of Ginkgo biloba (EGB 761), in prevention and treatment of the post-stress memory dysfunctions. The results showed that chronic restraint stress (2 h for 21 days) or an 'equivalent' dose of exogenous corticosterone (5 mg/kg) impaired nonspatial memory as measured by an object recognition test. In control rats, EGB 761 improved spatial and nonspatial memory in Morris water maze and object recognition tests. Preventive doses of EGB 761 (100 mg/kg) normalized cognitive deficits, seen in rats chronically stressed or treated with corticosterone in object recognition test, and improved memory processes in these rats measured by Morris water maze test. There was no influence of our treatments on locomotor exploratory activity and anxiety measured in open field and elevated 'plus' maze tests, making a contribution of unspecific motor and emotional effects of the used drugs to their performance in the memory tests improbable.

St John's wort (Hypericum perforatum) diminishes cognitive impairment caused by the chronic restraint stress in rats.

In this study we tested the hypothesis that St John's wort (Hypericum perforatum) may counteract stress-induced memory impairment. Object recognition test and Morris water maze were used to determine whether administration of H. perforatum (350 mg kg(-1) for 21 days), standardized to 0.3% hypericin content, protects against non-spatial and/or spatial memory impairments due to chronic restraint stress (2h daily for 21 days). A group of rats administered the exogenous corticosterone at the dose of 5 mg kg(-1) daily for 21 days, yielding its similar plasma levels as these observed in stress was run in parallel. In the first experiment all rats were tested for recognition memory in the object recognition test. On the following day, the animals were tested in open field and elevated "plus" maze to control for the contribution of respectively, motor and emotional effects of our treatments to the memory tests. In the second experiment, new group of stressed animals was tested for spatial memory in the water maze. We observed that H. perforatum prevented the deleterious effects of both chronic restraint stress and long-term corticosterone on learning and memory as measured in both, the object recognition and the water maze tests. The herb not only prevented stress- and corticosterone-induced memory impairments, but it significantly improved recognition memory (p<0.01) in comparison to control. These results suggest that H. perforatum has a potential to prevent stress memory disorders.