Developing Topics e11

treated with a high dose of apoaequorin. The groups were compared on

a neuropsychological test battery that includes object discrimination learn-

ing, performance on a visual search task and performance on a visuospatial

memory task. In a second experiment, we compared dogs treated with a high

dose of apoaequorin with dogs treated with Anipryl� on both discrimina-

tion learning task and a task set up to measure selective attention. Anipryl�is the only compound that has received regulatory approval for treatment of

cognitive dysfunction in dogs and was therefore used as a positive control.

Results: In the first experiment, the animals treated with apoaequorin

showed improved performance on both the discrimination learning task

and the visual search task (see Figure 1). By contrast the groups did not dif-

fer in performance on the spatial memory task (Figure 2). In the second ex-

periment, the groups treated with apoaequorin showed more accurate

learning than the Anipryl� group (Figure 3). When age and cognitive status

were controlled, the high dose apoaequorin group showed superior perfor-

mance the visual search task. Conclusions: The results suggest selective

cognitive benefits of calcium buffering protein on learning and on perfor-

mance on a task with attentional demands. Because the washin period for

these studies (4 days) was too short to produce a neuroprotective benefits,

these results, therefore, suggest that calcium buffering may be effective in

providing symptomatic benefits in learning and attention.

P4-284 SEROTONERGIC BLOCKADE PREVENTS

AGE-RELATED NEURODEGENERATION IN

C. ELEGANS MODEL OFALZHEIMER’S DISEASE

Jon Pierce-Shimomura, Ashley Crisp, University of Texas at Austin,

Austin, Texas, United States.

Background: Alzheimer’s disease (AD) is characterized by the selective

degeneration of cholinergic neurons involved in memory. Although the pre-

cise etiology of AD remains unclear, the amyloid-precursor protein (APP) is

clearly the causal agent in some cases including in Down syndrome where

an additional wild-type copy of APP is carried on the 21st chromosome.

Methods: Study of APP in mouse models can be challenging, however,

so we took advantage of the simple nervous system, short life span and

ease of molecular manipulation of the model nematode C. elegans. Specif-

ically, we have generated transgenic worms that express a single additional

wild-type copy of the worm APP ortholog (alp-1) or the human APP gene

with a pan-neuronal promoter. Results: We have found that, as in human

AD, overexpression of apl-1 or human APP results in age-related degener-

ation of a specific subset of cholinergic neurons in C. elegans. Deficits in

two natural behaviors, swimming and egg-laying, correlate with the accu-

mulation of APP protein in these neurons and their eventual death. In addi-

tion, through genetic and pharmacological analyses, we have found that

a specific serotonergic signaling pathway is both necessary and sufficient

for degeneration of these neurons. Conclusions: Our results are consistent

with studies in mice that have found that blockade of 5-HT6 signaling

prevents age-related decline in memory, and hint at a role for 5-HT6 in

APP-induced neurodegeneration. Moreover, if generalized to mammalian

systems, our results offer a warning that the beneficial effects of certain Alz-

heimer’s medications may be undermined by degeneration induced by non-

specific elevation of serotonin through SSRIs.

P4-285 TREATMENTOF EXPERIMENTAL AUTOIMMUNE

ENCEPHALOMYELITIS BYANTIOXIDANTS

(EXPERIMENTAL STUDY)

Tamar Sanikidze, Maia Beridze, Nino Intskirveli, Davit Davitashvili,

Levan Ratiani, Tbilisi State Medical University, Tbilisi, Georgia.

Background: Study purposed to determine the effectiveness of vitamin

treatment in experimental autoimmune encephalomyelitis (EAE) animal

model of multiple sclerosis (MS). Methods: Eighteen, 9-13 week old,

male Wistar rats were immunised by MOG injection. Clinical signs of

EAE scored by a masked investigator. After EAE exposition rats were

treated by vitamins (E, C). Blood was obtained from all rats before and after

immunization and on 7th day of treatment. ELISA method was used to de-

tect the serum cytokine contents of IL-6, IFN-g, IL-10. On 10th day of dis-

ease the rats were euthanized and transverse sections of spinal cord were

divided in 16 areas with score of 1 for each area showing lymphocyte infil-

tration or demyelination.Modeling the oxidative stress in cultured brain cor-

tex of the newborn albino rats was achieved with addition of H(2)O(2) into

the nutrient medium. In order to prevent an oxidative stress-induced cyto-

toxic effect, concomitantly with H(2)O(2), vitamins E and C were added

into the nutrient medium. Oxygen, lipid and nitrogen free radicals were reg-

istered by method EPR. Mann-Whitney U-test was used for determining the

level of significance of differences between sample means. Results: The

data, obtained in our study revealed decreasing of intensity of NO content

and increasing of spin trapped superoxid- (O(2-)) and lipoperoxid-radicals

(LOO.) in explants of brain cortex of the newborn albino rats cultured in ox-

idative stress conditions. These changes were attenuated following action of

vitamins E and C. In animal model on 7th day of treatment neurological de-

ficiency stayed unchanged in control and was ameliorated in experimental

group (p <0.05). Significant histopathological differences were found be-

tween control and experimental groups on 10th day of EAE. Serum levels

of IFN-g, IL-6 and IL-10 were elevated after exposition of EAE against

healthy rats, while on 7th day of treatment the experimental group revealed

the significant differences as compared to untreated control. Positive corre-

lation was found between IL-6 and IFN-g serum contents and neurological

deficiency on 7th day of disease (r ¼ +0.53, p <0.02 and r ¼ +0.49;

p <0.01). Conclusions: The main message of the presented research is

that antioxidant vitamins possess the unique protective contents and could

become the perspective medications for neuroprotection.

P4-286 TREATMENTOF EXPERIMENTAL AUTOIMMUNE

ENCEPHALOMYELITIS BYANTIOXIDANTS

(EXPERIMENTAL STUDY)

Tamar Sanikidze, Maia Beridze, Nino Intskirveli, Davit Davitashvili,

Levan Ratiani, Tbilisi State Medical University, Tbilisi, Georgia.

Background: Study purposed to determine the effectiveness of vitamin

treatment in experimental autoimmune encephalomyelitis (EAE).

Methods: Eighteen, 9-13 week old Wistar rats were immunised by MOG

injection. Clinical signs of EAE scored by a masked investigator. After

EAE exposition rats were treated by vitamins (E, C). Blood was obtained

from rats before and after immunization and on 7th day of treatment. The

serum cytokine contents of IL-6, IFN-g, IL-10. On 10th day of disease

the rats were euthanized and transverse sections of spinal cord were divided

in 16 areas with score of 1 for each area showing lymphocyte infiltration or

demyelination. Modeling the oxidative stress in cultured brain cortex of the

newborn albino rats was achieved with addition of H(2)O(2)into the nutrient

medium. In order to prevent an oxidative stress-induced cytotoxic effect

vitamins E and C were added into the nutrient medium. Oxygen, lipid and

nitrogen free radicals were registered by method EPR. Results: Eighteen,

9-13 week old, male Wistar rats were immunised by MOG injection. Clin-

ical signs of EAE scored by a masked investigator. After EAE exposition

rats were treated by vitamins (E, C). Blood was obtained from all rats before

and after immunization and on 7th day of treatment. ELISA method was

used to detect the serum cytokine contents of IL-6, IFN-g, IL-10. On 10th

day of disease the rats were euthanized and transverse sections of spinal

cord were divided in 16 areas with score of 1 for each area showing lympho-

cyte infiltration or demyelination. Modeling the oxidative stress in cultured

brain cortex of the newborn albino rats was achieved with addition of H(2)

O(2) into the nutrient medium. In order to prevent an oxidative stress-in-

duced cytotoxic effect, concomitantly with H(2)O(2), vitamins E and C

were added into the nutrient medium. Oxygen, lipid and nitrogen free rad-

icals were registered by method EPR. Mann-Whitney U-test was used for

determining the level of significance of differences between sample means.

Conclusions: The main message of the presented research is that antioxi-

dant vitamins possess the unique protective contents and could become

the perspective medications for neuroprotection.