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Autism spectrum disorders (ASD) are a group of pervasive developmental disorder. All of them have been developing from birth, accompanying human through whole life and have strong influence on social functioning, communication as well as cognitive abilities. Neurobiological research (e.g. neuroimaging) indicate that patients with ASD demonstrate impairments of amygdala structure and functioning. It is worth to compare if previous results in human may be observed in animals. The aim of this study was display that lesion of amygdala nuclei may indicate behaviors diagnostic for ASD. For that purpose on a group of male Wistar rats (n=40) was conducted an electrolytic lesion of basolateral (BLA) or centromedial (CeA) amygdala. Animals were divided into groups separately for BLA and CeA: control (without operation), sham (operation, without lesion) and lesioned. After convalescence rats were observed in different behavioral tests which measured social functioning (social interactions), anxiety (elevated plus maze), spatial memory (water maze) and communication (smell preference). Obtain results suggest that amygdala lesion decreased social functioning or anxiety (BLA and CeA), communication (BLA), motor activity (CeA). In spite of this spatial memory increased (BLA). On the base of behavioral results it is likely that lesion of amygdala nuclei may be perceive animal model for further studies. (support: NN303 819040).
BACKGROUND AND AIMS: Dopamine projections from the ventral tegmental area (VTA) – a somatodendritic region of mesolimbic system to the nucleus accumbens (particularly its shell region, AcbSh) – which constitutes its main terminal structure may play a central role in modulating affective states. In the present work, we used model of the VTA electrical stimulation-induced feeding reaction to research the role of AcbSh dopamine transmission in motivated behaviors. METHODS: In 5 rats (n=5) latency to eat was measured as a function of stimulation frequency before and after contralateral intraAcbSh injection of dopamine agonist D-amphetamine (dose 5.0 µg dissolved in 0.5 µl of water). This experimental method allowed us to distinguish between motivational vs. motor aspects of tested reaction. RESULTS: Inactivation of theAcbSh caused of itsintra injection of dopamine agonist D-amphetamine on the contralateral side (in relation to the hemisphere with VTA stimulation) affects motivational processes assessed by changes in frequency threshold for stimulation-induced feeding response. We observed increase, by more than 10% (about 13.37%), in the reaction threshold as compared with water control. Increase of the frequency threshold was accompanied by a parallel rightward shift of the function relating latency to feed to stimulation frequency, but statistical analysis of latency at the specific frequencies showed no significance (from 17.71 Hz to 81.38 Hz, P>0.05). Distilled water injected into the contralateral AcbSh (volume of the 0.5 µl), as a control group (n=5), did not cause any effect in comparison with the preinjection baseline. CONCLUSION: We conclude that the contralateral inactivation at the level of AcbSh does not impair of the behavior induced by activity of the dopaminergic cells at the level of VTA. Research was financed by the Polish National Science Centre (NCN); decision no: DEC-2013/09/D/NZ4/02499.
BACKGROUND AND AIMS: The activity of serotonin (5-HT) in the brain is strictly connected with the raphe nuclei. They are connected mainly with and influence the prefrontal cortex and limbic structures. Clinical studies indicate that 30% of people with autism spectrum disorder (ASD) have elevated platelet 5-HT level. The aim of the study was to investigate whether chronic (16-days) electrical stimulation of the raphe magnus (RMg) in rats can evoke behaviours comparable with the behaviours present in people with ASD. METHODS: Male Wistar rats were implanted with electrodes into the RMg under isoflurane anaesthesia. After 10-days convalescence chronic electrical stimulation began. Rats were divided into stimulated (n=6) and non-stimulated (sham/n=7) groups. Every day 25 stimulation trials were carried out, consisting of 30 s stimulation followed by 20 s interval. In sham group no current was passed through the electrode. During stimulations the locomotor activity was measured. Furthermore, the rats’ anxiety level and social responses were analyzed respectively on the 3rd and 8th day after the first stimulation. RESULTS: Locomotor activity was significantly higher in the experimental groups. At the intensity of 60–90 μA we observed rapid breathing, sniffing, and cage exploration, and at 110–140 μA – cage exploration and circular body movements. The anxiety level, analyzed as the time spent in closed arms in the elevated plus maze test, was comparable; nevertheless, social activity, measured in the three chamber test as a preference to a social stimulus, was reduced in the stimulated rats. CONCLUSIONS: Electrical stimulation of the RMg induced hyperlocomotor and reduced social behaviours, which are the symptoms often present in the course of ASD. The obtained results suggest that hyperactivity of the serotonergic system may play a role in the development of ASD. The research was funded by Young Researcher grant, 538-L124- B598-14
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.
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.
INTRODUCTION: Two notable targets of the pedunculopontine tegmental nucleus (PPN) circuitry, the substantia nigra (SN) and the ventral tegmental area (VTA), are implicated in locomotion and reward processing. A dysfunction of these regions occurs in Parkinson’s and related disorders as well as in various psychiatric conditions, and over the course of normal aging AIM(S): In the present study, we were interested in understanding NMDA-receptors involvement in the interactions between the PPN and SN/VTA midbrain complex. In order to obtain more insight into this process, we analyzed the number and the distribution of midbrain tyrosine hydroxylase positive cells (TH+). METHOD(S): All rats were implanted with bilateral stimulating electrodes in the VTA and with bilateral guide cannulas for intracerebral injections into the PPN. Immunohistochemistry for TH+ was used to measure the number of active dopaminergic neurons in midbrain (VTA-SN) of rats subjected to unilateral VTA electrical stimulation and local injection of MK‑801 (5 μg) or NMDA (3 μg) to the contralateral or ipsilateral hemispheres into the PPN (4 experimental groups). The control brains were from rats in which only the 14‑day unilateral electrical VTA‑stimulation was performed (control group). RESULTS: Immunohistochemical analysis revealed a decrease in the number of TH+ cells in the midbrain. When the main subdivisions of the VTA/SN were subjected to a separate analysis, a significantly lower number of TH+ cells were found in all experimental groups in the PBP (parabrachial pigmented nucleus), PB (paranigral nucleus) and SNc (SN, pars compacta), as compared to the control group. CONCLUSIONS: The level of NMDA receptor arousal in the PPN regulates the activity of the midbrain dopaminergic cells. FINANCIAL SUPPORT: The research was funded by the Polish National Science Center; decision no: DEC‑2013/09/N/NZ4/02195 and by the Faculty of Biology, University of Gdansk, Poland.
The central nucleus of the amygdala (CeA) is involved in fear conditioning and participates in euroendocrine response to stressful stimuli. In our previous study, we found that CeA also influences immune function, especially innate antitumore response. In the present study, we investigated the influence of 14-day electrical stimulation of the CeA on corticosterone level (CORT; determined by radioimmunoassay) and behavioral response: locomotor activity in the new environment (measured in the Opto Varimex Minor actometer), explorative and anxiety-like behavior [assessed in the openfield (OF) and in the elevated plus-maze (EPM) tests]. Male Wistar rats implanted with stimulating electrodes into the CeA were divided into groups: CeA 14-day electrical stimulation (n=20) and CeA sham (n=18). Current intensity (70–120 µA; 50 Hz) was raised incrementally in 30-s trials until behavioral reaction in the Opto Varimex Minor actometer was observed. OF and EPM tests were performed after termination of stimuation procedure. Electrical stimulation of the CeA caused augmentation of CORT level (P<0.001) correlated with an increase in the average number of movements in horizontal and vertical plane imitating escape behavior. These effects were accompanied by an increase in anxiety-related behavior in the EPM and decreased locomotor activity and exploration in the OF. We suggest the hormonal response to of the CeA stimulation plays a crucial role in the regulation of the behavioral response. Supported by The National Science Centre, grant number: NN303819040.
In our previous study we found that electrolytic lesion of the bed nucleus of the stria terminalis (BST) as well as the medial septal nucleus (MS) caused depression of the peripheral blood natural killer cell cytotoxicity (NKCC) in rats. In the present study we evaluated blood NKCC after 14 day electrical stimulation of the BST and the MS in conscious, freely behaving rats differing in responsiveness to novelty. Male Wistar rats divided into high (HR) and low (LR) responders to novelty, implanted with stimulating electrodes at the BST or at the MS, were subjected to 14 day electrical stimulation (constant current 0.1 ms duration cathodal pulses delivered at a frequency of 50 Hz during 30 min) of the BST and the MS. The chronic stimulation of the BST and the MS caused augmentation of blood NKCC in comparison to the sham operated group and to the baseline, which was more significant in HRs. A week after termination of the stimulation procedure NKCC returned to the baseline. The obtained results suggest that immunoenhancing effect on blood NK cell function is dependent on the behavioral outcome (intensive locomotor reaction) of the BST and the MS stimulation as well as on individual behavioral characteristics. This work was supported by a research grant NN303819040.
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