scholarly journals Chronic High-frequency Stimulation of the Subthalamic Nucleus Induces a Sustained Inhibition of Serotonergic System via Loss of Cell Phenotype

2022 ◽  
Author(s):  
Faisal Alosaimi ◽  
Yasin Temel ◽  
Sarah Hescham ◽  
Victoria Witzig ◽  
Faris Almasabi ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
Forced Swim Test ◽  
Cell Phenotype ◽  
High Frequency Stimulation ◽  
Calcium Indicator ◽  
Number Of Patients ◽  
Immobility Time ◽  
Mptp Treatment ◽  
Serotonergic Function ◽  
Stn Dbs

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a standard treatment in Parkinson’s disease (PD). However, in a considerable number of patients debilitating psychiatric side-effects occur. Recent research has revealed that external stimuli can alter the neurotransmitters’ homeostasis in neurons, which is known as “neurotransmitter respecification”. Herein, we addressed if neurotransmitter respecification could be a mechanism by which DBS suppresses the serotonergic function in the dorsal raphe nucleus (DRN) leading to mood changes. We infused transgenic 5-HT-Cre (ePet-cre) mice with AAV viruses to achieve targeted expression of eYFP and the genetically encoded calcium indicator GCaMP6s in the DRN prior to methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Mice received bilateral DBS electrodes in the STN and an optic fiber in the DRN for Ca2+ photometry. MPTP treated mice demonstrated behavioral and histological PD phenotype, whereas all STN-DBS animals exhibited an increased immobility time in the forced swim test, reduced Ca2+ activity, and loss of TPH2 expression in the DRN. Given the prominent role of Ca2+ transients in mediating neurotransmitter respecification, these results suggest a chronic loss of serotonergic phenotype in the DRN following STN-DBS. These findings indicate that loss of 5-HT cell phenotype may underlie the unwanted depressive symptoms following STN-DBS.

scholarly journals Analysis of Contact Position for Subthalamic Nucleus Deep Brain Stimulation-Induced Hyperhidrosis

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Chunhui Yang ◽  
Yiqing Qiu ◽  
Xi Wu ◽  
Jiali Wang ◽  
Yina Wu ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Control Group ◽  
Electrode Position ◽  
Improvement Rate ◽  
Number Of Patients ◽  
Significant Difference ◽  
Stn Dbs ◽  
Deep Brain

Objectives. To analyze the hyperhidrosis neural network structure induced by subthalamic nucleus (STN) - deep brain stimulation (DBS). Materials and Methods. Patients with Parkinson’s disease treated with STN-DBS in Changhai Hospital between July 1, 2015, and December 1, 2016, were analyzed retrospectively. Using records of side effects of the intraoperative macrostimulation test, patients with skin sweats were selected as the sweating group. Based on the number of cases in the sweating group, the same number of patients was randomly selected from other STN-DBS patients without sweating to form the control group. The study standardized electrode position with Lead-DBS software to Montreal Neurological Institute (MNI) standard stereotactic space to compare the differences in three-dimensional coordinates of activated contacts between groups. Results. Of 355 patients, 11 patients had sweats during intraoperative macrostimulation tests. There was no significant difference in the preoperative baseline information and the postoperative UPDRS-III improvement rate (Med-off, IPG-on) between groups. Contacts inducing sweat were more medial (X-axis) (11.02 ± 0.69 mm vs 11.98 ± 0.84 mm, P=0.00057) and more upward (Z-axis) (−7.15 ± 1.06 mm VS −7.98 ± 1.21 mm, P=0.032) than those of the control group. The straight-line distance between the center of the sweat contact and the nearest voxel of the red nucleus was closer than that of the control group (2.72 ± 0.65 mm VS 3.76 ± 0.85 mm, P=0.00012). Conclusions. STN-DBS-induced sweat indicated that the contact was at superior medial of STN.

Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

2020 ◽  
Vol 16 (9) ◽  
pp. 1319-1327
Author(s):  
Ferdous Khan ◽  
Syed A. Kuddus ◽  
Md. H. Shohag ◽  
Hasan M. Reza ◽  
Murad Hossain
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reduced Glutathione ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Glutathione Depletion ◽  
Swim Test ◽  
Stress Markers ◽  
Immobility Time ◽  
Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

The Effect of Fluoxetine and Ibuprofen on BCG-Induced Alteration in Pain Sensitivity in Mice

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Heba H El-Morsy ◽  
Wesam El-Bakly ◽  
Amany H Hasanin ◽  
May Hamza ◽  
M Abdel-Bary
Keyword(s):  
Drinking Water ◽  
Mechanical Allodynia ◽  
Formalin Test ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Control Group ◽  
Base Line ◽  
Immobility Time ◽  
Long Time ◽  
Incisional Pain

Abstract Clinical observations recognized the co-existence and interactions of pain and depression a long time, ago. The aim of this work was to study the effect of ibuprofen and fluoxetine on BCGinduced depressive-like behaviour, on formalin-induced pain, as well as on mechanical allodynia after planter incision in mice. BCG induced a depressive behaviour that was seen in the forced swim test (FST) and the tail suspension test (TST). It also induced a decrease in pain-related behaviour in the formalin test, and an increase in the baseline in mechanical allodynia test compared to the control group. Fluoxetine (80 mg/L of drinking water) showed a significant decrease in the immobility time in the FST and TST and enhanced pain related behaviour in formalin test in the BCG-inoculated group. However, it did not affect the increase in the pain threshold in the planter incision allodynia model. Adding ibuprofen to drinking water (0.2 g/L of drinking water), reversed the depressive like behaviour induced by BCG and enhanced pain-related behaviour in formalin test, in both the total pain-related behaviour and phase 2. It also prevented the increase in the base line induced by BCG. On the other hand, the incisional pain model was not affected by BCG inoculation except at the 2-hour time point, where it showed hypoalgesia, as well.

scholarly journals Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

2018 ◽  
Vol 33 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Jaclyn N Highland ◽  
Patrick J Morris ◽  
Panos Zanos ◽  
Jacqueline Lovett ◽  
Soumita Ghosh ◽  
...  
Keyword(s):  
Oral Administration ◽  
Learned Helplessness ◽  
Oral Bioavailability ◽  
Forced Swim Test ◽  
Abuse Potential ◽  
Absolute Bioavailability ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

Identification of Somatotopic Organization and Optimal Stimulation Site Within the Subthalamic Nucleus for Parkinson's Disease

2018 ◽  
Vol 17 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Tatsuya Sasaki ◽  
Ken Kuwahara ◽  
Ittetsu Kin ◽  
Mihoko Okazaki ◽  
Susumu Sasada ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Subthalamic Nucleus ◽  
Lower Limbs ◽  
Somatotopic Organization ◽  
First Contact ◽  
Upper Third ◽  
Stn Dbs ◽  
Passive Movements ◽  
Common Target ◽  
Deep Brain

Abstract BACKGROUND Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease. OBJECTIVE To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording. METHODS STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed. RESULTS The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and −0.45 ± 1.5, and −2.5 ± 1.1 and −3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position. CONCLUSION Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.

Failure to detect the action of antidepressants in the forced swim test in Swiss mice

2017 ◽  
Vol 30 (3) ◽  
pp. 158-167 ◽  
Author(s):  
Patrick R. Suman ◽  
Nathalia Zerbinatti ◽  
Lais Cristina Theindl ◽  
Karolina Domingues ◽  
Cilene Lino de Oliveira
Keyword(s):  
Sodium Butyrate ◽  
Antidepressant Treatment ◽  
Forced Swim Test ◽  
Dark Cycle ◽  
Swim Test ◽  
Swiss Mice ◽  
Forced Swim ◽  
Immobility Time ◽  
Effective Doses ◽  
High Doses

ObjectiveThe aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice.MethodsMale Swiss mice (n=6–8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1–30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes.ResultsAccording to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle.ConclusionData suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

scholarly journals TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model

2021 ◽  
Vol 11 (11) ◽  
pp. 1465
Author(s):  
Weifeng Peng ◽  
Yijun Shen ◽  
Qiang Wang ◽  
Jing Ding ◽  
Xin Wang
Keyword(s):  
Status Epilepticus ◽  
Latent Period ◽  
Lithium Chloride ◽  
Dendritic Spine ◽  
Forced Swim Test ◽  
Control Group ◽  
Comorbid Depression ◽  
Polyethylene Glycol 400 ◽  
Immobility Time ◽  
Pre Treatment

Epileptogenesis may be responsible for both of recurrent seizures and comorbid depression in epilepsy. Disease-modifying treatments targeting the latent period before spontaneous recurrent seizures may contribute to the remission of seizures and comorbid depression. We hypothesized that pre-treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase (sEH) inhibitor, which has anti-inflammatory and neuroprotective effects might rescue status epilepticus (SE)-induced dendritic spine loss and alleviate depressive behaviours. Rats were either pre-treated with TPPU (0.1 mg/kg/d) intragastrically or with vehicle (40% polyethylene glycol 400) from 7 days before to 7 days after SE that was induced with lithium chloride and pilocarpine intraperitoneally. Rats in the Control group were given saline instead. The forced swim test (FST) was performed on the 8th day after SE to evaluate the depression-like behaviours in rats. The results showed that seizures severity during SE was significantly decreased, and the immobility time during FST was significantly increased through TPPU pre-treatment. Moreover, pre-treatment with TPPU attenuated inflammations including microglial gliosis and the level of proinflammatory cytokine IL-1β in the hippocampus; in addition, neuronal and dendritic spine loss in the subfields of hippocampus was selectively rescued, and the expression of NR1 subunit of N-methyl-D-aspartate (NMDA) receptor, ERK1/2, CREB, and their phosphorylated forms involved in the dendritic spine development were all significantly increased. We concluded that pre-treatment with TPPU attenuated seizures severity during SE and depressive behaviours during the period of epileptogenesis probably by rescuing dendritic spine loss in the hippocampus.

scholarly journals A Meta-Analysis of the Effect of Subthalamic Nucleus-Deep Brain Stimulation in Parkinson's Disease-Related Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Diao ◽  
Yutong Bai ◽  
Tianqi Hu ◽  
Zixiao Yin ◽  
Huangguang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Motor Symptom ◽  
Stn Dbs ◽  
Deep Brain

Pain from Parkinson's disease (PD) is a non-motor symptom affecting the quality of life and has prevalence of 20–80%. However, it is unclear whether subthalamic nucleus deep brain stimulation (STN–DBS), a well-established treatment for PD, is effective forPD-related pain. Thus, the objective of this meta-analysis was to investigate the efficacy of STN-DBS on PD-related pain and explore how its duration affects the efficacy of STN-DBS. A systematic search was performed using PubMed, Embase, and the Cochrane Library. Nine studies included numerical rating scale (NRS), visual analog scale (VAS), or non-motor symptom scale (NMSS) scores at baseline and at the last follow-up visit and therefore met the inclusion criteria of the authors. These studies exhibited moderate- to high-quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. Random effect meta-analysis revealed a significant change in PD-related pain as assessed by NMSS, NRS, and VAS (P &lt;0.01). Analysis of the short and long follow-up subgroups indicated delayed improvement in PD-related pain. These findings (a) show the efficacy of STN-DBS on PD-related pain and provide higher-level evidence, and (b) implicate delayed improvement in PD-related pain, which may help programming doctors with supplement selecting target and programming.Systematic Review Registration: This study is registered in Open Science Framework (DOI: 10.17605/OSF.IO/DNM6K).

scholarly journals Resolution of tardive tremor after bilateral subthalamic nucleus deep brain stimulation placement

2020 ◽  
Vol 11 ◽  
pp. 444
Author(s):  
Samir Kashyap ◽  
Rita Ceponiene ◽  
Paras Savla ◽  
Jacob Bernstein ◽  
Hammad Ghanchi ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Orofacial Dyskinesia ◽  
Major Depressive ◽  
History Of ◽  
Stn Dbs ◽  
Common Manifestation ◽  
Tardive Syndrome ◽  
Deep Brain

Background: Tardive tremor (TT) is an underrecognized manifestation of tardive syndrome (TS). In our experience, TT is a rather common manifestation of TS, especially in a setting of treatment with aripiprazole, and is a frequent cause of referrals for the evaluation of idiopathic Parkinson disease. There are reports of successful treatment of tardive orofacial dyskinesia and dystonia with deep brain stimulation (DBS) using globus pallidus interna (GPi) as the primary target, but the literature on subthalamic nucleus (STN) DBS for tardive dyskinesia (TD) is lacking. To the best of our knowledge, there are no reports on DBS treatment of TT. Case Description: A 75-year-old right-handed female with the medical history of generalized anxiety disorder and major depressive disorder had been treated with thioridazine and citalopram from 1980 till 2010. Around 2008, she developed orolingual dyskinesia. She was started on tetrabenazine in June 2011. She continued to have tremors and developed Parkinsonian gait, both of which worsened overtime. She underwent DBS placement in the left STN in January 2017 with near-complete resolution of her tremors. She underwent right STN implantation in September 2017 with similar improvement in symptoms. Conclusion: While DBS-GPi is the preferred treatment in treating oral TD and dystonia, DBS-STN could be considered a safe and effective target in patients with predominating TT and/or tardive Parkinsonism. This patient saw a marked improvement in her symptoms after implantation of DBS electrodes, without significant relapse or recurrence in the years following implantation.

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