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Biomedical subjects

W Honig

Publications and source records attributed to W Honig.

15 recordsLinked to original sources
PubMed2001

Apolipoprotein E protects against neuropathology induced by a high-fat diet and maintains the integrity of the blood-brain barrier during aging.

SUMMARY: The present study provides evidence that chronic intake of a high-fat diet induces a dramatic extravasation of immunoglobulins, indicating alterations in blood-brain barrier (BBB) functioning, in the brains of apolipoprotein E (apoE)-knockout mice, but not of C57Bl/6 control mice. Using sodium fluorescein as a marker for the permeability of the BBB, we found additional support for age-related disturbances of BBB function in apoE-knockout mice. Behavioral analysis of apoE-knockout mice compared with C57Bl/6 mice indicated that they were also less efficient in acquiring the spatial Morris water maze task. Furthermore, apoE-knockout mice are known to develop severe atherosclerosis, which is exacerbated with a high-fat diet. We therefore compared the apoE-knockout mice with the apoE3-Leiden transgenic mice, which are known to develop atherosclerosis. However, apoE3-Leiden mice that were kept on a high-fat, high-cholesterol diet and that developed atherosclerosis to an extent similar to the apoE-knockout mice, showed no signs of BBB disturbances. These results indicate for the first time that apoE plays an essential role in the maintenance of the integrity of the BBB during aging and that it protects the brain from neuropathology induced by a high-fat diet. We therefore hypothesize that the role of apoE in the maintenance of the integrity of the BBB may be the mechanism by which apoE affects the progression of neurodegeneration, as seen in Alzheimer's disease.

Aging↗
PubMed2001

Long-term consequences of repeated pentobarbital anaesthesia on choice reaction time performance in ageing rats.

Recent studies have suggested that anaesthesia may be a factor in cognitive decline with age. We examined the effect of repeated (eight times) anaesthesia with pentobarbital on reaction time performance in rats in a longitudinal study. Treated rats had faster response times and made more premature responses than the control rats when they were older than 21 months. The results suggest that repeated anaesthesia during the lifespan can lead to an increase in impulsivity, as assessed by a choice reaction time test, during the later stages of life in the rat. These findings support the theory that repeated anaesthesia is a biological factor that affects cognitive ageing.

Adjuvants, Anesthesia↗
PubMed2000

Nitric oxide synthase does not mediate neurotoxicity after an i.c.v. injection of streptozotocin in the rat.

In the present study we evaluated the possible role of nitric oxide (NO) in mediating neuronal damage in middle-aged rats after an i.c.v. injection of streptozotocin (STREP). An i.c.v. injection of STREP has been reported to decrease the central metabolism of glucose. This inhibition of the energy metabolism after STREP treatment might induce an excitotoxic mechanism, which may lead to the stimulation of NO synthase and, consequently to the synthesis of NO. On the other hand, STREP might induce oxidative stress directly by liberation of NO from its nitroso moiety. To investigate whether NO synthase is involved in a possible excitotoxic mechanism after STREP treatment, some of the rats treated with STREP (1.25 mg/ kg in 4 microl, bilaterally 2 microl/injection site) were also treated with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.p. 10 min, 6, 24 and 96 h after STREP injection). To investigate whether NO liberated from STREP may be responsible for neurotoxic effects, one additional group of control rats received an i.c.v. injection of the NO donor sodium nitroprusside (SNP, 10 microg in 4 microl). We found that STREP affected the behavioral performances in the open field and two-way active avoidance task. In addition, immunostaining for glial fibrillary acidic protein, an indicator of reactive astroglial changes to neuronal damage, showed that this was mainly located in peri- and paraventricular regions of the third and lateral ventricles, like for instance in the septum, caudate putamen and hippocampus. L-NAME treatment had no protective effect on the behavioral impairments and neuronal damage of STREP-treated rats. This suggests that the neuronal damage of STREP may still be a result of the decrease in the central energy metabolism, but without the involvement of NO synthase. This was supported by measuring, using immunostaining, the NO-mediated cyclic GMP production by the enzyme soluble guanylyl cyclase in cortical slices, i.e. L-NAME did not prevent NO production after STREP administration in vitro. In addition, it was found that SNP liberated NO in vitro, whereas in vivo SNP administration did not lead to any behavioral and neuronal deficits at all. However, the present study cannot exclude the involvement of NO liberated from STREP in neuronal damage.

Animals↗
PubMed1999

Metrifonate improves working but not reference memory performance in a spatial cone field task.

The effects of metrifonate (3, 10 and 30 mg/kg, p.o.) on the working and reference memory performance of the rat were assessed in a spatial cone field task. The highest dose of metrifonate (30 mg/kg) improved the working memory performance, whereas none of the doses affected the reference memory performance. Other parameters of spatial discrimination performance were not affected by metrifonate treatment. The present results suggest that metrifonate has cognition-enhancing properties which are likely to be related to aspects of (spatial) working memory.

Animals↗
PubMed1999

Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS.

There are various clinical and non-clinical studies that have indicated that phosphatidylserine (PS) treatment can improve cognitive functions in humans and other animals. However, treatment with PS derived from bovine cortex is not desirable because of possible transfer of infectious diseases. The present study investigated the cognition-enhancing properties of different types of PS in rats. Seventeen-month-old male Fischer 344 rats were treated daily with a dose of 15 mg/kg of PS derived from bovine cortex (BC-PS), soybean (S-PS), egg (E-PS), or vehicle (n = 9 for each group). The effects of treatment were evaluated in three different behavioral tests. An open field test was conducted to examine the effects of treatment on psychomotor behavior. Two other tests (Morris water escape task and two-way active avoidance) assessed treatment effects on the cognitive performance of rats. Treatment with the different forms of PS did not affect the psychomotor or spatial discrimination performance of the rats. In accordance with previous studies, the cognition-enhancing effects of BC-PS were observed in the two-way active avoidance task. It appeared that the cognition-enhancing effects of S-PS were not different from those of BC-PS. The performance of rats treated with E-PS did not deviate from that of vehicle-treated rats. On the basis of the present study, it was concluded that S-PS, but not E-PS, may have comparable effects on cognition when compared with BC-PS.

Animals↗
PubMed1999

Intra-striatal haloperidol and scopolamine injections: effects on choice reaction time performance in rats.

In this study the behavioral consequences of intra-striatal haloperidol and scopolamine injections were examined using a reaction time task. Haloperidol was found to increase the response time of the rats and had a modest effect on the motor components of the task. The manner in which haloperidol affected the response time distribution suggested that this drug affected attentional functions. Scopolamine did not affect the reaction time or motor performance in the reaction time task. However, a clear decrease in the number of completed trials and an increase in anticipatory responses was observed. At present no ready explanation could be given for the behavioral effects of scopolamine. The present data suggest that although dopamine and acetylcholine are intimately related in the striatal network and have been supposed to have antagonistic functions, the behavioral consequences of blockade of dopamine and acetylcholine receptors are dissimilar.

Animals↗
PubMed1999

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats.

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L-arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.

Animals↗
PubMed1998

State-dependent impairment in object recognition after hippocampal NOS inhibition.

In the present study we investigated the consequences of hippocampal nitric oxide synthase (NOS) inhibition on the performance in an object recognition task in rats. In a first study we injected Nomega-nitro-L-arginine (L-NA) into the hippocampus directly after the first trial. One hour later the discrimination performance of the animals was assessed. It was found that 10 microg and 30 microg, but not 3 microg, L-NA impaired the performance of the rats. In a second study in which we injected L-NA 45 min before the first trial no effects of treatment (10 microg and 30 microg) were observed. Since treatment with 30 microg has been found to inhibit hippocampal NOS almost completely and lasts longer than 2 h, it was concluded that hippocampal NOS inhibition induced a state-dependent performance deficit. Consequently, studies that examine the effects of NOS inhibition on cognitive functions should take this confounding effect into account.

Animals↗
PubMed1998

Acute effects of acetyl-L-carnitine on sodium cyanide-induced behavioral and biochemical deficits.

In the present study we investigated the effects of acute treatment with acetyl-L-carnitine (50 mg/kg, i.v. 90 min before the sodium cyanide injection) on a sodium cyanide-induced behavioral deficit in the Morris water escape task. In a first experiment the spatial discrimination performance of the rats was found to be dose-dependently impaired after an i.c.v. injection of sodium cyanide (2.5 and 5.0 microg). Acute treatment with acetyl-L-carnitine was found to increase the behavioral deficit after sodium cyanide. These findings were replicated in a second experiment. Based on these results it can be argued that an acute administration of acetyl-L-carnitine appears to potentiate a sodium cyanide-induced behavioral deficit. An additional in vitro experiment with rat brain synaptosomes showed clear effects of administered sodium cyanide on the energy-dependent incorporation of inositol into phosphoinositides and on the ATP concentration. In vitro acetyl-L-carnitine administration had no effect on the sodium cyanide-induced energy depletion. The negative behavioral findings are in contrast with our previously found protective effect of chronic treatment with acetyl-L-carnitine (via drinking water) on the sodium cyanide-induced behavioral deficit. Since chronic acetyl-L-carnitine treatment has no effect on the phosphoinositide metabolism it was suggested that acetyl-L-carnitine may act via the formation of an ATP-independent reservoir of activated acyl groups. Thus, fatty acids as acylated derivatives can be used for reacylation processes during an acute period of energy depletion. However, we have no clear explanation for the discrepancy in behavioral results between the chronic vs acute treatment of acetyl-L-carnitine at present. Further research is needed to characterize the mechanism of action of acetyl-L-carnitine in relation to sodium cyanide.

Acetylcarnitine↗
PubMed1998

Effects of haloperidol and d-amphetamine on working and reference memory performance in a spatial cone field task.

The present study was designed to examine the effects of haloperidol (0.03, 0.1 mg/kg, intraperitoneal (i.p.)) and d-amphetamine (0.3, 1.0 mg/kg, i.p.) in a cone field task in which spatial working and reference memory (WM and RM, respectively) were assessed simultaneously. The apparatus is a large open field in which 16 cones are placed with four cones baited by placing a food reward in the top. After food-deprived rats had acquired this task they showed a high level of performance, that is avoided visits to non-baited cones (RM) and made few revisits to baited cones (WM). Haloperidol had a greater negative effect on RM than on WM performance, but also decreased the number of food rewards collected. On the other hand, the high dose of d-amphetamine induced a clear WM performance deficit, whereas RM performance was only marginally affected. The present study suggests that spatial discrimination performance can be dissociated using the measures RM and WM in the present task. Further, the deficits induced by haloperidol and d-amphetamine may not be specifically related with impaired mnemonic functions.

Animals↗
PubMed1995

Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L-carnitine.

Treatment of rats with i.c.v. injected streptozotocin (STREP) may provide a relevant model of neurodegeneration that is induced by a decrease in the central metabolism of glucose. Acetyl-L-carnitine (ALCAR) enhances the utilization of alternative energy sources and by such a mechanism of action ALCAR could antagonize the effects of STREP treatment. In this study the effects of chronic treatment with ALCAR were evaluated on spatial discrimination learning in the Morris task and choline acetyltransferase (ChAT) activity of middle-aged STREP-treated rats. Chronic treatment with ALCAR attenuated both the STREP-induced impairment in spatial bias and the decrease in hippocampal ChAT activity. These findings indicate that ALCAR treatment has a neuroprotective effect, although further studies are needed to characterize the mechanism of action of ALCAR in this model.

Acetylcarnitine↗
PubMed1993

Behavioural and biochemical effects of acute central metabolic inhibition: effects of acetyl-l-carnitine.

In the present study we evaluated a new method to assess the behavioural and biochemical effects of a brief period of acute hypoxia in the brain. In this method, cyanide is injected into the lateral ventricles. Spatial navigation performance in a Morris task was found to be impaired 1 and 5 min after an i.c.v. injection of 5.0 micrograms cyanide but not after 2.5 micrograms cyanide. Increased rate of phosphatidic acid formation, reflecting increased phospholipase C activity, were observed after injection of 5.0 micrograms cyanide, indicating that energy-dependent phosphoinositide metabolism was affected. Chronic treatment with acetyl-l-carnitine attenuated the cyanide-induced behavioural deficit, but had no effect on energy-dependent phosphoinositide metabolism. The results suggest that, in this model, acetyl-l-carnitine may act via free fatty acid metabolism, by increasing the reservoir of activated acyl groups which are involved in the reacylation of membrane phospholipids.

Acetylcarnitine↗
PubMed1992

Effects of intra-hippocampal scopolamine injections in a repeated spatial acquisition task in the rat.

The involvement of hippocampal cholinergic synapses in spatial discrimination learning was evaluated by locally administering scopolamine into the hippocampus. Sixteen 16-month-old male Lewis rats received bilaterally implanted cannulae aimed at the dorsal part of the hippocampus. The rats were trained on a repeated acquisition test in the Morris water-escape task. In this procedure the invisible platform is randomly moved from day to day to one of four possible locations. Thus, the rat has to learn to localize the platform from day to day. On each day the rats received four pairs of trials. Scopolamine injections (35 micrograms in 1 microliter per hippocampus) were given to one group (n = 8) on days 5 and 7. On days 6 and 8 all rats received saline injections. Place learning was retarded in the scopolamine-treated rats during the first swims of pairs of trials. During second swims the scopolamine-treated rats showed a general performance deficit, indicating that first and second swims were differentially affected. The data support the hypothesis that cholinergic neurotransmission in the dorsal hippocampus is involved in spatial learning processes.

Analysis of Variance↗