Haloperidol-induced parkinsonism is attenuated by varenicline in mice

2018 ◽  
Vol 29 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Amit K. Sharma ◽  
Sparsh Gupta ◽  
Ranjan K. Patel ◽  
Neeta Wardhan

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). However, there is no known drug to stop/slow down this neurodegeneration. Varenicline is an anti-smoking drug and has the potential to prevent neurodegeneration. Thus, the present study was designed to evaluate the effect of varenicline in animal models of PD. Methods Levodopa and haloperidol were administered in doses of 30 and 1 mg/kg, intraperitoneally (i.p.), respectively. Group 1 was administered haloperidol; groups 2, 3 and 4 were administered haloperidol along with varenicline in doses of 0.5, 1.5 and 2.5 mg/kg, i.p., respectively and group 5 was administered levodopa along with haloperidol. Varenicline was administered daily, 30 min prior to the administration of haloperidol. Varenicline was administered for the first 8 days, and then from the 9th day until the 15th day. Behavioral assessment (rotarod and catalepsy tests) was performed on days 9 and 15. Assessment of striatal dopamine levels and histopathology were also performed. Results In the haloperidol-treated groups, significant decrease in latency to fall off (on rotarod) and increase in catalepsy duration (in catalepsy test) were observed as compared to the control group. In the levodopa-treated group, significant increase in latency to fall off the rotarod and significant decrease in catalepsy duration were observed as compared to the haloperidol-treated groups. Further, on day 9, varenicline (2.5 mg/kg) significantly increased the latency to fall off the rotarod, while varenicline (0.5 and 1.5 mg/kg) did not cause any significant change in latency to fall off the rotarod as compared to the haloperidol-treated group. On day 15, significant increase in latency to fall off the rotarod was observed in varenicline (at all doses) as compared to the haloperidol-treated group. In the catalepsy test, the varenicline-treated (at all doses) groups showed significant decrease in duration of catalepsy on day 9 and day 15 as compared to the haloperidol-treated group. Significant decrease in striatal dopamine levels was observed among the haloperidol-treated groups as compared to the control group. Further, varenicline-treated (at all doses) and levodopa-treated groups showed significant increase in striatal dopamine levels when compared with the haloperidol-treated group. In histology, varenicline (0.5 mg/kg) showed moderate decrease in neurons, while varenicline (1.5 and 2.5 mg/kg) showed mild decrease in neurons. However, the levodopa-treated group did not show any significant decrease in neurons. Thus, varenicline has shown promising results and has provided novel strategy for the treatment of PD.

2018 ◽  
Vol 17 (2) ◽  
pp. 132-143 ◽  
Author(s):  
Mehmet Eray Alcigir ◽  
Halef Okan Dogan ◽  
Begum Yurdakok Dikmen ◽  
Kubra Dogan ◽  
Sevil Atalay Vural ◽  
...  

Background & Objective: Aroclor 1254 is a widespread toxic compound of Polychlorinated Biphenyls (PCBs), which can create significant nervous problems. No remedies have been found to date. The aim of this study was to reveal the damage that occurs in the central nervous system of rat pups exposed to Aroclor 1254 in the prenatal period and to show the inhibiting effect of curcumin, which is a strong anti-oxidant and neuroprotective substance. Method: The study established 3 groups of adult female and male Wistar albino rats. The rats were mated within these groups and the offspring rats were evaluated within the group given Aroclor 1254 only (n=10) and the group was given both Aroclor 1254 and curcumin (n=10) and the control group (n=10). The groups were compared in respect of pathomorphological damage. The immunohistochemical evaluation was made of 8-hydroxdeoxyguanosine (8-OHdG), 4-hydroxynoneal (4HNE), myelin basic protein (MBP) expressions and TUNEL reaction. The biochemical evaluation was made of the changes in the TAS-TOS and Neuron Specific Enolase (NSE) levels. Damage was seen to have been reduced with curcumin in the 8OHdG and TUNEL reactions, especially in the forebrain and the midbrain, although the dosage applied did not significantly change TAS and TOS levels. Consequently, it was understood that Aroclor 1254 caused damage in the central nervous system of the pup in the prenatal period, and curcumin reduced these negative effects, particularly in the forebrain and the midbrain. Conclusion: It was concluded that curcumin could be a potential neuroprotective agent and would be more effective at higher doses.


2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Qianli Tang ◽  
Qiuyan Jiang ◽  
Suren R. Sooranna ◽  
Shike Lin ◽  
Yuanyuan Feng ◽  
...  

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.


2020 ◽  
Vol 11 (1) ◽  
pp. 280-284 ◽  
Author(s):  
Julietpoornamathy J ◽  
Parameswari C.S.

In medical sciences, toxicity is an area wherein extensive studies have been carried to improve the diseases as well as to prevent. So, there is a high requirement for novel and improved alternative therapeutic strategies to manage diseases. The liver is the largest gland in the body, which executes several important mechanisms; it stores minerals and vitamins and releases them in periods of need. The main aim of this study was to give a closer insight into potent non- toxic compounds that is capable of modifying the responses. Animals were divided into five equal groups viz control (Group 1), administered with food and water ad libitum, (Group 2) administered with olive oil, (Group 3) administered with zingerone, (Group 4) administered with concanavalin A, (Group 5) administered with cyclosporine A followed by zingerone. Our results revealed significant changes in liver marker enzymes and liver histology of zingerone treated rats when compared to control rats.  A corollary, zingerone has no toxic effect on hepatocytes and was found to be safe at a dose of 10mg/kg b wt and also ameliorates hepatotoxicity.


2021 ◽  
Vol 11 (11) ◽  
pp. 249-265
Author(s):  
B. Lobasyuk ◽  
L. Bartsevich ◽  
A. Zamkovaya

Justification. Mental retardation is a persistent decrease in human cognitive activity against the background of organic damage to the central nervous system. Neurophysiological diagnostics, in particular electroencephalography (EEG), most adequately reflects the morpho-functional state of the central nervous system, which is the basis of the mechanisms of mental activity, and the originality of the bioelectrical activity of the brain can be considered as the main indicator that determines a decrease in the level of intellectual development and, thereby, characterizes this state. This provision actualizes the search for highly informative indicators of the originality of the bioelectrical activity of the brain in children with intellectual disabilities. Purspose. With the use of periodometric analysis investigate EEG’s indicators and interhemispheric asymmetry of rhythms amplitudes in MR patients. Materials and methods. The EEG was recorded in a state of calm wakefulness with closed eyes with Neuron-Spectrum-2 electroencephalograph. Differences in indicators were tracked using the calculation of the coefficient of compliance (CC), EEG functional asymmetry coefficients in amplitude were determined, too. Results. It was revealed that in MR patients the amplitudes of the rhythms were greater than in healthy subjects. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. Duration indices in the delta, theta and alpha ranges of the EEG in mental retardation compared with the control group were increased, and the indices of the duration of beta rhythms - decreased. When analyzing FMPA in MR persons it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices. Conclusions 1. With mental retardation, the amplitudes of the rhythms were greater than in healthy people. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. 2. The indices of duration in the delta, theta and alpha ranges of the EEG of MR subjects were increased, and the indices of the duration of beta rhythms – decreased. 3. When analyzing FMPA in MR persons, it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices.


2021 ◽  
Vol 11 (5) ◽  
pp. 970-975
Author(s):  
Khold Al Ahdal ◽  
Laila Al Deeb ◽  
Mohammed S. Bin-Shuwaish ◽  
Rana S. Al-Hamdan ◽  
Modhi Al Deeb ◽  
...  

The aim of the present study was to evaluate the efficacy of interfacial bonding between resin cement and titanium alloy conditioned with different Photobiomodulataion Therapy (PBT) in comparison with conventional regimes. Seventy-five samples of titanium bar were segmented polished; and based on conditioning regime divided into five groups (15 each specimens). Group 1: No treatment (control), Group 2: Sand blasting with 120 µm Al2O3, Group 3: Er,Cr:YSGG (ECL), Group 4: Er:YAG laser (EYL), Group 5: Nd:YAG laser (NYL). After different conditioning regimes, resin cement was mixed and applied. All specimens were thermocycled for 500 cycles and positioned on universal testing machine for shear bond strength testing. Modes of failure was assessed by a single examiner using stereomicroscope at 40× magnification. Three pairs of specimens in each group were sputter coated and scanning electron microscope (SEM) images were taken at 1000× magnification using 20 Kv. The highest SBS values were observed in group 2 (14.25±2.29 MPa) and the lowest bond values were displayed in group 1 (6.98 ±0.59 MPa). Titanium alloy abutments conditioned with different laser prototypes ECL (11.22±1.40 MPa), EYL (9.29±1.22 MPa) and NYL (9.12 ±1.84 MPa) exhibited comparable SBS (p > 0.05). Adhesive failures were primarily dominant among all experimental groups. Photo-biomodulation in the form of ECL lasers has the potential to be used as a supplement to sandblasting procedure in conditioning of cement retained titanium alloy implant abutments.


1984 ◽  
Vol 247 (4) ◽  
pp. R655-R662
Author(s):  
S. Koyama

The time course of changes in mean blood pressure (MBP), heart rate (HR), and renal blood flow (RBF) in a control group of anesthetized dogs given only endotoxin (1 mg/kg iv) was compared with groups pretreated with alpha-antagonists either intravenously or intracisternally (ic). The decreases in MBP and RBF in the control group were abolished by intracisternal prazosin (0.1 mg/kg ic). MBP response to endotoxin after intravenous prazosin did not differ from that of the control group; however, the endotoxin-induced decrease in RBF after intravenous prazosin was significantly greater than that in the control group. HR responses to endotoxin were not altered by either intracisternal or intravenous prazosin. MBP and RBF responses to endotoxin after intravenous or intracisternal yohimbine (0.5 mg/kg iv or ic) did not differ from the control responses. However, significant differences occurred in the time course of changes in HR only when yohimbine was administered intracisternally. These observations suggest that the hypotensive effect and reduction of RBF due to endotoxin may be mediated by alpha 1-adrenoceptors at least in the central nervous system and that of HR response may be mediated alpha 2-adrenoceptors.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Dornoush Jafarpour ◽  
Seyed Shahram Shekarforoush ◽  
Hamid Reza Ghaisari ◽  
Saeid Nazifi ◽  
Javad Sajedianfard

The aim of this study was to investigate the efficacy of two probiotics and a prebiotic (inulin) on intestinal microbiota of rats exposed to cadmium and mercury. Fifty-four male Wistar rats were randomly divided into nine groups. All groups except control group were fed standard rat chow with 5% inulin and treated as follows: i) control (standard diet), ii) <em>Lactobacillus</em> <em>plantarum</em>- treated group (1×109 CFU/day), iii) <em>Bacillus</em> <em>coagulans</em>-treated group (1×109 spores/day), iv) cadmium-treated group (200 μg/rat/day), v) L. plantarum and cadmium-treated group, vi) <em>B. coagulans</em> and cadmium-treated group, vii) mercury-treated group (10 μg/rat/day), viii) <em>L. plantarum</em> and mercurytreated group, ix) <em>B. coagulans</em> and mercurytreated group. Cadmium, mercury and probiotics were daily gavaged to individual rats for 42 days. Treatment effects on intestinal microbiota composition of rats were determined. Data showed that cadmium and mercury accumulation in rat intestine affected the gastrointestinal tract and had a reduction effect on all microbial counts (total aerobic bacteria, total anaerobic bacteria, total Lactic acid bacteria, <em>L. plantarum</em> and <em>B. coagulans</em> counts) compared to the control group. It was also observed that application of synbiotics in synbiotic and heavy metals-treated groups had a significant effect and increased the number of fecal bacteria compared to the heavy metals groups. Based on our study, it can be concluded that <em>L. plantarum</em> and <em>B. coagulans</em> along with prebiotic inulin play a role in protection against cadmium and mercury inhibitory effect and have the potential to be a beneficial supplement in rats’ diets.


2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Vitor Cesar Nakamura ◽  
Simony Hidee Hamoy Kataoka ◽  
Giulio Gavini ◽  
Patrícia Helena Ferrari ◽  
Silvana Cai

Objective. To evaluate through FE-SEM the cleanliness and dentinal alterations promoted by different methods of dental sample preparation.Methods. Twenty-five human single-rooted teeth were used. The teeth were cleaned and autoclaved in wet medium and randomly divided into 5 groups (), according to the preparation methods employed—control group: no solutions applied; group 1: cement removal and irrigation with 5.25% % EDTA for 4 minutes each; group 2: 17%  % NaOCl (4 minutes ultrasonic bath); group 3: cement removal and 17%     buffer solution + distilled water (10 minutes ultrasonic); group 4: 17%   NaOCl (3 minutes ultrasonic bath). Specimens were analyzed by field emission scanning electron microscope (FE-SEM), at 1500x magnification. Data were submitted to qualitative analysis according to a scoring system and submitted to Kruskal-Wallis test.Results. In ascending order, as to bind parameters, (i) cleanliness: control, group 2, group 3, group 5, and group 4, (ii) dentinal alterations: group 1, group 5, group 2, group 3, and group 4.Conclusion. The proposed protocol was suitable for subsequent microbiological contamination, because it showed less dentinal morphological alterations with increased removal of organic waste.


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