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1

Mild laboratory stress elevates FOS expression in the amygdala and hypothalamus in rats high-responsive to novelty

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Majkutewicz I., Myslinska D., Jerzemowska G., Plucinska K., Wrona D.
Acta Neurobiologiae Experimentalis
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2011
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tom 71
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nr S
Responsiveness to novelty is often used as a measure of inter-individual vulnerability to stress loads and drug abuse. The aim of this study was to determine the relationship between individual behavioral profile and brain structures activation. Possible influence of stressful laboratory routines on manifestation of these individual differences was investigated. Male Wistar rats (n=21) were subjected to the novelty test and divided into high (HR) and low (LR) responders to a new environment according to median. Randomly chosen 6 LRs and 5 HRs rats were handled and carried out from the vivarium to the laboratory for nine days (carried group), remaining rats stayed in their home cages (control group, 5 HRs and 5 LRs). One week after the last carrying, an immunohistochemical detection of Fos protein in selected brain areas was performed. Carried HRs showed significantly higher Fos expression in all studied nuclei of the amygdala and most of the hypothalamic areas as compared to LRs and also to control rats. Carried LRs showed elevated density of Fos+ cells only in the stressrelated paraventricular and supraoptic hypothalamic nuclei. Surprisingly, inter-individual (HR vs LR) differences in brain activation was found in carried rats only. We conclude that mild stress evoked by some laboratory routines reveals constitutive differences between the individuals reflected by an increased activity of the amygdala and hypothalamus.
2

Stimulation of the vertal induces hippocampal theta rhythm and c-fos expression in the rat brain

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Majkutewicz I., Kusmierczak M., Blajet M., Orzel-Gryglewska J., Jurkowlaniec-Kopec E.
Acta Neurobiologiae Experimentalis
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2009
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tom 69
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nr 3
Our previous study indicated that microinjection of procaine or electrolytic lesion of the ventral tegmental area (VTA) suppressed hippocampal theta rhythm in urethane-anaesthetized rats. The aim of this study was to verify the hypothesis that electrical stimulation of the VTA induces hippocampal theta rhythm and to fi nd brain structures particularly active during this phenomenon and probably involved in its mechanism. The study was performed on urethane anaestethized male Wistar rats with an electrode implanted unilaterally in the VTA or zona incerta (ZI – control group). Stimulation was applied as 0.1-ms rectangular impulses of 50 Hz frequency and duration of 30 s at 10-min intervals. VTA stimulation within the current intensity range of 100–240 mA evoked hippocampal theta rhythm, manifested as synchronization of the EEG signal and an increase in the power at 3–6 Hz band. ZI stimulation did not elicit such effects. After VTA stimulation we also found induction of c-fos expression in brain regions connected to the VTA: nucleus accumbens, lateral septum, or engaged in the regulation of hippocampal theta rhythm: medial septum, midline thalamic nuclei, hypothalamic nuclei, pedunculopontine, laterodorsal and cuneiform tegmental nuclei. The results indicate that the VTA may be a part of the brainstem theta synchronizing system and may infl uence the hippocampal EEG through indirect pathway via hypothalamus and the medial septum, simultaneously increasing thalamic activity.
3

Beneficial effect of high frequency stimulation of subthalamic nucleus on Vermicelli handling test behavior after partial nigral depletion in rats

86%
Grembecka B., Dzbenska E., Ziołkowska N., Majkutewicz I., Plucinska K., Ptaszek K., Wrona D.
Acta Neurobiologiae Experimentalis
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2017
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tom 77
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nr Suppl.1
INTRODUCTION: Loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) lead to motor deficits observed in patients with Parkinson’s disease (PD). The neurosurgical therapy of choice is high frequency stimulation of subthalamic nucleus (HFS-STN) improved motor control. The motor impairment depends on the progression of nigral degeneration and in rats model of PD may be measured by Vermicelli handling test (VHT). AIM(S): The purpose of this study was to evaluate the influence of HFS‑STN on VHT behavior in rats with early PD model, induced by 6-OHDA infusion into SNpc. METHOD(S): Male Wistar rats (n=12) were implanted unilaterally for HFS-STN and received a intranigral infusion of 6-OHDA. 5 days before infusion rats were trained on handle 7 cm lengths of vermicelli pasta and acclimated to video recording. Then, rats were subjected to HFS-STN for 7 days (1 h daily) at intensity just below triggering forelimb dyskinesia or SHAM stimulation. The VHT was providing in both groups each day. The number of adjustments made with each forepaw per each pasta piece, which allow definite Vermicelli asymmetry ratio (VAR) and time to eat were analyzed. PD model have been verified by the detection of tyrosine hydroxylase positive neurons in substantia nigra pars compacta. For a statistical analysis of the results, SPSS software was used. RESULTS: U-Man Whitney tests showed that HFS-STN stimulated rats consumed the pasta significantly faster than the SHAM (p≤0.001) across days 1st, 2nd, 5th, 6th, and 7th after 6-OHDA infusion. Interestingly, the VAR was higher in HFS-STN rats in 1st and 4th (p≤0.001 and p≤0.01) days in comparison to SHAM animals. The atypical behaviors were not observed. CONCLUSIONS: The HFS-STN applied in partial dopamine depleted rats influence on time of pasta eating and enhanced asymmetries in forepaw adjustments. The obtained results suggest that faster eating after HFS-STN may be related with amelioration of orofacial movements or increased motivation for food, but not with forepaw manipulation improvement. FINANCIAL SUPPORT: Supported by the Department of Animal and Human Physiology found 530-L124-D248-16.
4

Effect of sprint interval exercises on peripheral level of neuroprotective proteins and human cognitive abilities

86%
Kujach S., Olek R., Kubiak R., Chroboczek M., Majkutewicz I., Laskowski R.
Acta Neurobiologiae Experimentalis
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2017
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tom 77
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nr Suppl.1
INTRODUCTION: Overwhelming amount of scientific evidence suggest that regular physical activity is effective in the prevention of chronic diseases. Most adults do not meet even the minimum guidelines for regular physical efforts. Numerous studies have shown that the main reason for the absence of regular exercise is lack of time. Interval training is a potent, time‑efficient therapeutic intervention that is more effective than continuous exercise. Certain evidence indicates that Sprint Interval Exercises (SIE) may result in rapid phenotypic changes in both the cardiovascular system and in the skeletal muscle. However, studies evaluating the effects of SIE on cognitive functions are limited. AIM(S): The aim of this study was to investigate whether SIE affects the peripheral level of selected neuroprotective proteins (BDNF, IGF-1, VEGF) as well as modulate human cognition. METHOD(S): The study involved Gdansk University of Physical Education and Sport students. Subjects were divided in two groups: Sprint Interval Exercise and Control group. To evaluate serum concentrations of BDNF, IGF-1 and VEGF the ELISA method was applied. Cognitive testing include: Stroop interference test, Adult Intelligence Scale Wechsler WAIS-R – Repeat numbers subtest and Trail Making Test part A and B. RESULTS: SIE contributed to a significant, transient increase of three neurotrophins BDNF, IGF-1, VEGF. Obtained results of cognitive functions indicated that acute SIE significantly improved selected human cognitive abilities performance. CONCLUSIONS: The results indicate that proposed SIE can induce positive changes in neuroprotective proteins improving human cognition. Given the growing number of people with cognitive impairment around the world, there is a recognized need for further research, explaining how specific exercise can influence the improvement of these functions. Such studies can be viewed as another important step towards the development of non-pharmacological therapeutic strategies in improving human cognitive function. FINANCIAL SUPPORT: This work was supported by the Polish National Science Center under Grant No: 2012/07/N/ NZ7/01902.
5

Subthalamic nucleus deep brain stimulation influence on erythrocyte number and hemoglobin levels in a rat model of early Parkinson's disease

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Grembecka B., Koriat P., Podlacha M., Majkutewicz I., Ptaszek K., Plucinska K., Wrona D.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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nr Suppl.1
INTRODUCTION: Subthalamic nucleus deep brain stimulation (STN-DBS) is most effective treatment for Parkinson’s disease (PD) motor symptoms. A number of epidemiological studies have recently highlighted the association between hemoglobin (HGB) levels and PD risk. Interestingly, several lines of evidence confirm that STN-DBS increases regional cerebral blood flow and oxygen concentrations in target brain areas. AIM(S): Considering the close association between oxygen concentration, red blood number (RBC), and HBG, we hypothesized that enhanced blood flow during STN-DBS may influence peripheral RBC parameters in a rat model of early PD. METHOD(S): Male Wistar rats were implanted unilaterally for STN-DBS and received intranigral (substantia nigra pars compacta, SNpc) infusion of 6‑OHDA. After recovery, rats were subjected to STN-DBS for 7 days (1h daily, n=6) or SHAM stimulation (control, n=6). Immediately after collection, peripheral blood samples were analyzed using automated hematology analyzer (Cell Dyn 3700). The RBC number, hematocrit percentage (HCT), HGB concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were measured. PD model was verified by the detection of tyrosine hydroxylase positive neurons in SNpc. For a statistical analysis of the results, SPSS 22.0 software was used. RESULTS: The Student’s t‑test showed that STN‑DBS rats had a significantly higher number of RBC in comparison to the SHAM rats (t(10)=‑2.912; p≤0.05). The HCT percentage slightly increased but differences did not reach statistical significance. Mann‑Whitney U tests showed that HGB level was higher in STN-DBS rats (Z=‑1.290; p≤0.05). CONCLUSIONS: The STN-DBS applied in a rat model of early PD has an influence on RBC number and HGB level. The obtained results suggest that there are peripheral compensation mechanisms for the increased oxygen demand during STN‑DBS in rats. FINANCIAL SUPPORT: Department of Animal and Human Physiology fund.
6

Dimethyl fumarate alleviates reference memory impairment and modulates brainderived neurothropic factor expression in streptozotocin-induced rat model Alzheimer's disease

86%
Kurowska E., Majkutewicz I., Myslinska D., Grembecka B., Grzybowska M., Podlacha M., Rucinski J.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
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nr Supl.
BACKGROUND AND AIMS: Intracerebroventricular (icv) injection ofstreptozotocin (STZ) induces brain glucose hypometabolism, memory impairment, progressive cholinergic deficit, activation of microglia, oxidative stress and neurodegeneration. It is used as an animal model of sporadic form of Alzheimer’s disease (AD). The aim of this study was to determine if dimethyl fumarate (DMF), oral anti-oxidative and immunosuppressive drug, alleviates spatial reference memory impairments in STZ-icv induced rat model of AD. Additionally, the expression of brain derived neurotrophic factor (BDNF) was measured. METHODS: There were four experimental groups: STZ DMF (n=8) – STZ-icv infused and fed with 0.4% DMF fodder for three weeks until spatial memory test of Morris, STZ CTR (n=8) – STZ-icv infused and fed with standard fodder, and VEH DMF and VEH CTR groups (n=10) – vehicle-icv infused and fed with 0.4% DMF or standard fodder, respectively. A three-day Morris water maze test (four trials per day with unchanged platform location) and the probe test on the fourth day were performed. Rats were sacrificed and brain subjected to immunofluorescent BDNF labeling. RESULTS: The latency to reach the platform in the second and third day of testing was significantly longer in the STZ CTR rats than in the remaining groups, which showed tendency to reduce the latency day by day. STZ DMF rats did not differ in the results of the spatial memory test of Morris from control VEH CTR and VEH DMF groups. All STZ rats showed reduced BDNF expression in the hippocampus, but in the hypothalamus STZ DMF showed more BDNF+ cells than STZ CTR rats. CONCLUSION: Oral medication with DMF alleviates spatial reference memory impaired after STZ-icv infusion. The decrease of BDNF expression after STZ-icv infusion was prevented by DMF in the hypothalamus. The study was financed by the National Science Centre Poland on the basis of decision DEC-2013/09/D/NZ4/01658.
7

Lesion and stimulation of the ventral tegmental area increases cholinergic activity in the rat brain

86%
Majkutewicz I., Cecot T., Jerzemowska G., Trojniar, Jaskulski M., Wrona D.
Acta Neurobiologiae Experimentalis
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2010
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tom 70
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nr 1
Our previous study indicated that unilateral lesion of the ventral tegmental area (VTA) facilitates contralateral VTA stimulation-induced feeding or exploration. The present study was aimed to determine the possible role of the central cholinergic systems in this effect. Immunohistochemistry for choline acetyltransferase (ChAT) was used to measure the number of active cholinergic neurons in their major groups (Ch1–Ch6) and in striatal regions in rats subjected to unilateral electrocoagulation and contralateral VTA electrical stimulation (L/S group) in comparison to the unilaterally stimulated (S), unilaterally lesioned (L) and sham (Sh) groups. The study showed that unilateral VTA lesion increased (as compared to Sh group) the number of ChAT+ neurons in the Ch1–Ch3 and unilateral VTA stimulation increased the number in the Ch1 and the ventral pallidum only. The most sensitive to these changes in the mesolimbic system were cholinergic structures providing hippocampal afferentation. Surprisingly, there was no significant increase in the number of ChAT+ neurons in the L/S group. The obtained results did not confirm any evident influence of the cholinergic systems on the VTA lesion-induced facilitation of the behavioral response evoked by contralateral VTA stimulation.
8

Streptozotocin and dimenthyl fumarate decreases plasma tumor necrosis factor Alpha concentration in rats

86%
Grzybowska M., Podlacha M., Majkutewicz I., Kurowska E., Myslinska D., Grembecka B., Wrona D.
Acta Neurobiologiae Experimentalis
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2015
|
tom 75
|
nr Supl.
BACKGROUND AND AIMS: This study aims to determine if dimethyl fumarate (DMF), antioxidant having immunosuppressive properties, taken orally for three weeks will affect plasma tumor necrosis factor  alpha (TNF-α) concentration in an animal model of sporadic form of Alzheimer’s disease (sAD) induced by intracerebroventricular (icv) injection of betacytotoxic drug, streptozotocin (STZ). METHODS: Blood samples from young, male Wistar rats divided into four groups: STZ DMF (subjected to icv injection of STZ, fed with 0.4% DMF fodder), VEH DMF (subjected to icv injection of vehicle, fed with 0.4% DMF fodder), STZ CTR (subjected to icv injection of STZ, fed with standard fodder), VEH CTR (subjected to icv injection of vehicle, fed with standard fodder) were taken one hour after Morris water maze test finishing. Then, TNF-α concentration was determined with ELISA method using a Rat TNF-α ELISA Kit. RESULTS: Injections of STZ in rats being on the control feed (STZ/ CTR) significantly decreased (P≤0.05) the  plasma concentration of  TNF-α (22±2 pg/ml; mean±SE) as compared to the controls (VEH/CTR: 33±3 pg/ml). Moreover, within the STZ/DMF group, a significant (P≤0.01) decrease in the concentration of  TNF-α (22±0.8 pg/ml)  as compared to the controls  (VEH/DMF: 30±2 pg/ ml), was observed. CONCLUSION: The obtained results indicate that streptozotocin injection and feeding with dimethyl fumarate of the streptozotocininduced sAD rats reduce such a peripheral blood pro-inflammatory cytokine level as TNF-α.
9

Dimethyl fumarate prevents spatial working memory impairment and does not affect brain IL-6 expression in streptozotocininducted rat model of Alzheimer's disease

86%
Majkutewicz I., Kurowska E., Myslinska D., Grembecka B., Grzybowska M., Podlacha M., Rucinski J.
Acta Neurobiologiae Experimentalis
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2015
|
tom 75
|
nr Supl.
BACKGROUND AND AIMS: Animal model of sporadic form of Alzheimer Disease (AD) evoked by intracerebroventricular (icv) injection of betacytotoxic drug, streptozotocin (STZ), reflects memory impairments, brain hypometabolism, cholinergic deficit, activation of microglia and neurodegeneration found in AD patients. Brain inflammation is important factor contributing to exacerbation of AD symptoms, but some studies show neuroprotective properties of pro-inflammatory cytokine IL-6. The aim of this study was to determine if dimethyl fumarate (DMF), which has anti-oxidative and immunosuppressive properties, can alleviate spatial working memory impairments in STZ-icv induced rat model of AD and change the expression of IL-6 in the brains. METHODS: Four experimental groups were separated: STZ DMF (n=8) – STZ-icv infused and fed with 0.4% DMF fodder for three weeks until spatial memory test of Morris, STZ CTR (n=8) – STZicv infused and fed with standard fodder, and VEH DMF and VEH CTR groups (n=10) – vehicle-icv infused and fed with 0.4% DMF or standard fodder, respectively. Morris water maze testing was performed for three days, with four trials per day with unchanged platform location, and rats were then sacrificed and brains subjected to immunofluorescent IL-6 labeling. RESULTS: The latency to reach the platform in each trial was significantly longer in the STZ CTR rats than in the remaining groups. STZ CTR was the only group which did not decrease the latency and the distance swum to platform in the consecutive trials. STZicv infused rats  (STZ CTR and STZ DMF groups) had also lower number of the IL-6 expressing cells in the hippocampus and the hypothalamus than control VEH CTR rats. CONCLUSION: Oral medication with DMF prevents spatial working memory impairment evoked by STZ-icv infusion, but has no influence on the central expression of IL-6. The study was financed by the National Science Centre Poland on the basis of decision DEC-2013/09/D/NZ4/01658.
10

Genistein-mediated lysosomal degradation of main patogenic factors of Alzheimer’s disease as a novel therapeutic strategy

86%
Pierzynowska K., Podlacha M., Gaffke L., Majkutewicz I., Mantej J., Myslinska D., Wegrzyn G.
Acta Biochimica Polonica
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2018
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tom 65
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nr S2
11

Brain-derived neurotropic factor (RDNF) expression and behavioral response during stimulation of bed nucleus of the stria terminalis (BST) in rats

72%
Myslinska D., Majkutewicz I., Podlacha M., Ciepielewski Z., Karnia M., Wadolowska A., Rucinski J., Siudak M., Zajaczkowski S., Wrona D.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
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nr Supl.
BACKGROUNDANDAIMS: The bed nucleus of the stria terminalis (BST) is a part of “the extended amygdala”, a formation responsible for emotional aspects of behavior. The BST is considered as a site of convergence of information from brain regions associated with the control of emotional, cognitive, autonomic and behavioral responsesto stress and noxiousstimuli. On the basis of our previousstudy we assumed that the BST also influenced the primary antitumor immune response. In the present study we investigated the influence of 14-day electrical stimulation of the BST on the brain-derived neurotrophic factor (BDNF) expression and behavioral response. METHODS: Male Wistar rats implanted with electrodes into the BST were divided into groups: BST stimulated and BST sham. The intensity of stimulation current (120–160 µA; 50 Hz) was determined individually for each stimulated rat to induce a behavioral response such a locomotor reaction. The current intensity was raised incrementally in 30 s trials (30 trials/day, 20 s rest between the trials). Behavioral reaction was measured in the Opto Varimex Minor actometer during stimulation procedure. BDNF was detected during immunofluorescence procedure. RESULTS: The stimulation of the BST caused induction of BDNF expression in brain cortical and subcortical motor structures: the frontal primary motor cortex (areas FR1 and FR2), prefrontal cortex, ventral tagmental area, as well as in the central amygdala nucleus and in the hypothalamus: the paraventricular and the supraoptic nuclei, the medial preoptic and the lateral areas positively correlated with the augmentation of the behavioral activity which appeared as locomotor activity (increase in the average number of movements in horizontal and vertical plane). CONCLUSION: This suggests that the behavioral outcome of the BST stimulation, imitating physical exercise, could be responsible for brain BDNF synthesis observed in the study. Supported by: NN303819040.
12

Proces autofagii indukowany genisteiną jako nowe podejście w leczeniu chorób neurodegeneracyjnych

72%
Pierzynowka K., Podlacha M., Myslinska D., Majkutewicz I., Mantej J., Niedzialek N., Wegrzyn A., Wegrzyn G.
Postępy Mikrobiologii. Suplement
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2017
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tom 56
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nr 2
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