Measuring the potency labelling of onabotulinumtoxinA (Botox<Superscript>®</Superscript>) and incobotulinumtoxinA (Xeomin<Superscript>®</Superscript>) in an LD50 assay

The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox^®) and incobotulinumtoxinA (Xeomin^®) are compared in the Xeomin^® batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox^® and Xeomin^® can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs.     

Sapphire<Superscript>®</Superscript> platinum detachable coil experience in a tertiary-care facility

Background

The Guglielmi Detachable Coil introduced by the Boston Scientific Corporation has been widely used for endovascular coiling of aneurysm. Recently, Sapphire® platinum detachable coils (eV3, Irvine, CA) have been introduced for aneurysm coiling. Herein, we report our clinical experience with the Sapphire® coil to evaluate the incidence of coil related complications and the rate of aneurysm occlusion.

Methods

Consecutive patients who underwent embolization with Sapphire® detachable coils were prospectively enrolled from January 2004 to September 2004 and the data were retrospectively analyzed. Patient demographics, including age, gender, presenting symptoms, Hunt and Hess grade, Fisher grade and locations of the vascular anomalies were collected. Additionally, complications associated with the coils and rates of aneurysm occlusion were observed and the data compiled.

Results

29 patients underwent Sapphire® coil embolization for intracranial aneurysms. Mean age was 50 ± 18 (mean ± SD) years with 81% being females. Aneurysm neck reconstruction was required in 7 cases, 6 with Neuroform stent (5 unruptured aneurysms) and 1 with balloon assistance (ruptured aneurysm). In 7 cases, Sapphire® coils were used along with other coils. There were no events of thromboembolism or ruptures of aneurysms during coil embolization. However, multi-diameter coils demonstrated stretching in 4 stent-assisted cases without any adverse consequences. Complete occlusion of the aneurysm was achieved in 79.31% of the patients, neck remnant in 6.89, and partial coiling was achieved in 13.79%.

Conclusion

The Sapphire® coil could safely be used in the treatment of both ruptured and unruptured aneurysms. However, multi-diameter non-stretch resistant coils may be associated with coil stretching when used in conjunction with a stent. Further study is still required for definitive results.

     

Reduced hippocampal neurogenesis in the GR<Superscript>+/−</Superscript> genetic mouse model of depression

Glucocorticoid receptor (GR) heterozygous mice (GR^+/− ) represent a valuable animal model for major depression. GR^+/− mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR^+/− animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR^+/− genotype on neurogenesis in vivo. In a 2 × 2 design, GR^+/− mice and GR^+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR^+/− genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR^+/− mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.     

Efficacy and safety of nabiximols (Sativex<Superscript>®</Superscript>) on multiple sclerosis spasticity in a real-life Italian monocentric study

Multiple sclerosis (MS) patients frequently suffer from limb spasticity and pain despite antispastic treatments. To investigate nabiximols efficacy and safety in a real-world monocentric Italian cohort, the following data were collected at baseline, week 4, 14 and 48: Ambulation Index (AI), 10-min walking test (10MWT), combined Modified Ashworth scale (cMAS), scores at numerical rating scale for spasticity (sNRS) and pain (pNRS). Responder status was defined as a ≥20 % reduction in sNRS after 4 weeks of treatment. 144 MS patients (123 progressive and 21 relapsing-remitting) complaining of moderate-to-severe spasticity (mean sNRS: 7.5) were included: 138 (95.8 %) completed the first month of therapy and were classified as follows—23.2 % were non-responders, 5.1 % were responders but discontinued treatment due to side effects, 71.7 % were responders with a mean 32 % reduction in sNRS (p < 0.001). In responders sNRS further decreased between 4 and 14 weeks (p = 0.03). Similarly, pNRS improvement was seen during the first month and between 4 and 14 weeks (p < 0.001 and p = 0.004, respectively). Moreover, at 4 weeks responders showed a significant (p < 0.05) improvement in cMAS, AI and 10MWT, which was maintained at 14 weeks. At 1-year follow-up, a benefit was still evident on spasticity and painful symptoms with a low drop-out rate. Confusion/ideomotor slowing, fatigue and dizziness were the most frequent side effects; no major adverse events were reported. Shorter disease duration at treatment start was associated with better response. This real-world study confirms nabiximols efficacy and safety in the treatment of MS-related spasticity and pain, which is maintained up to 48 weeks.     

Predictors of adolescents’ mental health problems in Saudi Arabia: findings from the Jeeluna<Superscript>®</Superscript> national study

Background

Depression and anxiety among adolescents require further attention as they have profound harmful implications on several aspects of adolescents’ wellbeing and can be associated with life threatening risk behaviors such as suicide.

Objective

To examine the underlying risk factors for feeling so sad or hopeless and for feeling worried among adolescents in Saudi Arabia.

Methods

Data from Jeeluna^® national survey was used. A cross-sectional, multi-stage, stratified, cluster random sampling technique was applied among a sample of students aged 10–19 years attending intermediate and secondary schools in Saudi Arabia. A self-administered questionnaire assessing several domains, including feeling so sad or hopeless and worried, was used to collect data. Logistic regression models were fitted to determine the different factors associated with mental health.

Results

A sample of 12,121 students was included in this study. Feeling so sad or hopeless and feeling worried were significantly more prevalent among females and older adolescents (p < 0.0001). The results showed that poor relationship with parents, negative body image, and chronic illness to be significantly associated with feeling so sad or hopeless and worried.

Conclusions

Symptoms suggestive of mental health problems among adolescents in Saudi Arabia are prevalent and deserve special attention. Adopting effective strategies, including regular screening and intervention programs are highly needed to better address, detect, and control early signs of these problems.

     

The use of the Actiwatch–Neurologica<Superscript>®</Superscript> system to objectively assess the involuntary movements and sleep–wake activity in patients with mild–moderate Huntington’s disease

Huntington’s disease (HD) is a neurodegenerative disorder characterised by cognitive, psychiatric and motor abnormalities including a range of involuntary movements. Currently, assessment of these movements involves the use of subjective rating scales such as the Unified Huntington’s Disease Rating Scales (UHDRS) for bradykinesia and maximal dystonia and chorea, without any objective measures. As new therapies emerge, it is critical that an objective means of evaluating these abnormal movements is developed and we have investigated the use of a wrist–worn activity monitor, the Actiwatch–Neurologica^®, to determine whether these movements can be measured. In addition, this activity monitor and subjective reports were used to objectively measure the degree of sleep disruption in these same HD patients.Eight patients with mild-moderate HD and 8 age– and sex–matched control subjects wore the monitor for a period of 48 hours and recorded in a diary whether they were asleep or awake for each hour over the 2–day period. Assessment of various movement parameters revealed that HD patients exhibited significantly greater total and maximum activity levels and spent longer performing high acceleration movements while they were awake compared with controls. During sleep, patients not only showed significantly more activity and spent more time making high acceleration movements, but they also made significantly more movements than control subjects.These results demonstrate that the Actiwatch–Neurologica^® activity monitor can be used to objectively assess movements in HD patients during periods of high activity as well as during sleep.     

<Superscript>18</Superscript>F-FP-CIT PET imaging and SPM analysis of dopamine transporters in Parkinson’s disease in various Hoehn &; Yahr stages

To investigate the usefulness of 18F-FP-CIT PET for assessing the severity of Parkinson’s disease (PD) at various clinical stages, 41 patients with PD were divided into early (Hoehn&Yahr I-II, n = 23) and advanced (Hoehn&Yahr III-IV, n = 18) subgroups. 18F-FP-CIT PET was performed in these patients and 12 normal subjects. 18F-FP-CIT uptake in striatal subregions and its correlation with UPDRS were first evaluated by ROI analysis, and between-group differences were also analyzed by Statistical Parametric Mapping (SPM). Our results showed that striatal 18F-FP-CIT binding were significantly reduced to 70.9% (caudate), 46.8% (anterior putamen) and 24.0% (posterior putamen) in early PD compared with that of the control, and to 52.0%, 34.5% and 16.5% correspondingly in advanced PD, respectively. There was significant negative correlation between total motor UPDRS score of all parkinsonian patients and 18F-FP-CIT uptake in caudate nucleus (r = −0.53, p < 0.001), anterior putamen (r = −0.53, p < 0.001) and posterior putamen (r = −0.61, p < 0.001). SPM comparison of 18F-FP-CIT uptake between early or advanced PD and the control group showed significant decline in striatum, predominantly localized on the contralateral side and in the dorsal-posterior putamen. These results indicate that 18F-FP-CIT PET can serve as a suitable biomarker to represent the severity of PD in early and advanced stages. Received in revised form: 11 June 2006     

Reduced cardiac <Superscript>123</Superscript>I-MIBG uptake reflects cardiac sympathetic dysfunction in de novo Parkinson’s disease

It remains unclear whether cardiac iodine-123-labeled metaiodobenzylguanidine (¹²³I-MIBG) uptake is clinically related to autonomic dysfunction on conventional autonomic function testing in de novo Parkinson’s disease (PD). We therefore studied the relation between cardiac ¹²³I-MIBG uptake and cardiovascular autonomic dysfunction in patients with de novo PD. The subjects were 26 patients with de novo PD. The ratio of the average pixel count in the heart to that in the mediastinum was calculated to derive the cardiac ¹²³I-MIBG uptake. Cardiovascular autonomic function was evaluated on the basis of cardiovascular autonomic response on the Valsalva maneuver (VM), and systolic blood pressure response (SBP) on head-up tilt-table testing (HUT). Patients with de novo PD had significantly reduced cardiac ¹²³I-MIBG uptake as compared with controls (1.58 ± 0.43 vs. 2.25 ± 0.34, p = 0.0001) and cardiovascular autonomic response on the VM. No significant difference in the fall in SBP on HUT was found between patients with de novo PD and the controls. Cardiac ¹²³I-MIBG uptake in de novo PD was not significantly related to vasomotor sympathetic function, baroreceptor reflex gain, cardiac parasympathetic function, or the changes in SBP on HUT. Cardiac ¹²³I-MIBG uptake was, however, significantly related to the blood pressure overshoot in phase IV of the VM (r = 0.648, p = 0.0003). Cardiac ¹²³I-MIBG uptake began to decrease in association with the reduction in the overshoot of phase IV on the VM. Cardiac ¹²³I-MIBG uptake clinically reflects cardiac sympathetic dysfunction in de novo PD.     

Comparison of α-dihydroergocryptine and levodopa monotherapy in Parkinson’s disease: assessment of changes in DAT binding with [<Superscript>123</Superscript>I]IPT SPECT

Summary. Putative neurotoxic actions of levodopa and neuroprotective effects of dopamine agonists, as indicated by laboratory and animal studies, provide the rationale to study their effect on the progression of Parkinsons disease. Aim of this pilot study was to compare the effects of monotherapy with the dopamine agonist -dihydroergocryptine (DEC) versus monotherapy with levodopa on nigrostriatal dopaminergic neurons as measured with dopamine transporter (DAT) SPECT. 25 PD patients (H&Y stages 1 to 2.5) entered this study and were treated in a randomized fashion either with DEC (101±39mg) or levodopa (369±51mg) monotherapy. 16/25 patients (8 per group) terminated the study after 52 weeks. In each patient SPECT investigations with [¹²³I]IPT were performed at baseline and after 52 weeks to assess changes of specific DAT binding over time. Changes in clinical symptoms were assessed by UPDRS score. The mean annual decline rate in striatal IPT-binding was lower in the DEC group (8.4%) compared to the levodopa group (10.4%). The difference was most accentuated in the putamen (DEC: 7.3%; levodopa: 16.2%; p=0.16). Due to the small sample size and the relatively short observation period, however, group differences did not reach a statistical significant level. The results of this pilot study suggest that as compared to levodopa monotherapy DEC may have beneficial effects on decline of dopamine transporter binding similar to those recently described for pramipexole.     

The use of onabotulinum toxin A (Botox<Superscript>®</Superscript>) in the treatment of chronic migraine at the Parma Headache Centre: a prospective observational study

Chronic migraine is a debilitating headache, whose treatment is often complicated by the concomitant overuse of symptomatic medication and by the poor efficacy of standard prophylactic treatments. The PREEMPT studies have demonstrated the efficacy and tolerability of onabotulinum toxin A (Botox^®) in the treatment of this headache type. Data about its use in clinical practice are still scarce. Our study evaluated all subjects with chronic migraine who were treated with onabotulinum toxin A between February 2014 and November 2015 at the Parma Headache Centre. Botox was injected according to the PREEMPT paradigm every 3 months. The data about variations in the number of headache days and in symptomatic medication intake before and after the Botox injections were collected from the patients’ headache diaries. The study also evaluated tolerability to treatment, disability, and depressive symptoms. Of the 52 treated subjects, 14 received Botox treatment for at least 9 months and showed a significant decrease in the median number of headache days (from 19 to 14.5, p = 0.011) and in the median number of days of symptomatic medications intake and symptomatic drugs. Overall, the treatment was well tolerated. The average MIDAS and BDI-II scores after 9 months were reduced, though not significantly. The treatment with Botox proved effective and well tolerated in our clinical practice. Further studies on larger patient samples will help shed light on the persistence of the drug’s effect at long term and identify the predictive factors of response to treatment.     

Muscarinic acetylcholine receptor status in Alzheimer’s disease assessed using (R,R) <Superscript>123</Superscript>I-QNB SPECT

Abstract Background One of the most characteristic changes in Alzheimer's disease (AD) is a deficit in cortical cholinergic neurotransmission and associated receptor changes. Objective To investigate differences in the distribution of M1/M4 receptors using (R, R) ¹²³I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in patients with mild/moderate AD and agematched controls. Also, to compare ¹²³I-QNB uptake to the corresponding changes in regional cerebral blood flow (rCBF) in the same subjects. Methods Forty two subjects (18 AD and 24 healthy elderly controls) underwent ¹²³IQNB and perfusion ^99mTc-exametazime SPECT scanning. Image analysis was performed using statistical parametric mapping (SPM99) following intensity normalisation of each image to its corresponding mean whole brain uptake. Group differences and correlations were assessed using two sample t-tests and linear regression respectively. Results Significant reductions in ¹²³I-QNB uptake were observed in regions of the frontal rectal gyrus, right parahippocampal gyrus, left hippocampus and areas of the left temporal lobe in AD compared to controls (height threshold of p ≤ 0.001 uncorrected). Such regions were also associated with marked deficits in rCBF. No significant correlations were identified between imaging data and clinical variables. Conclusion Functional impairment as measured by rCBF is more widespread than changes in M1/M4 receptor density in mild/moderate AD, where there was little or no selective loss of M1/M4 receptors in these patients that was greater than the general functional deficits shown on rCBF scans.     

Pramipexole versus sertraline in the treatment of depression in Parkinson’s disease

In addition to treating the motor symptoms of Parkinson's disease, the dopamine agonist pramipexole has shown an antidepressant effect. The trials, however, included patients with motor complications, raising the question of whether the antidepressant benefit represented only a treatment-related motor improvement. To address this issue, we have conducted a 14-week randomized trial comparing pramipexole with an established antidepressant in patients without motor complications. At seven Italian centers, 67 Parkinsonian outpatients with major depression but no history of motor fluctuations and/or dyskinesia received open-label pramipexole (at 1.5 to 4.5 mg/day) or sertraline (at 50 mg/day). In both groups, the Hamilton Depression Rating Scale (HAM-D) score decreased throughout 12 weeks of treatment, but in the pramipexole group the proportion of patients who recovered, as defined by a final HAM-D score 相似文献   

Platelet phospholipase A<Subscript>2</Subscript> activity in Alzheimer’s disease and mild cognitive impairment

Summary. Phospholipase A₂ (PLA₂) controls the metabolism of phospholipids in cell membranes. In the brain, PLA₂ influences the processing of the amyloid precursor protein (APP) and thus the production of the amyloid-beta peptides (A), which are the major components of the senile plaques in Alzheimers disease (AD). Reduced PLA₂ activity has been reported in brain and in platelets of AD patients. In the present study we investigated PLA₂ activity in platelets from 21 AD patients as compared to 17 healthy elderly controls and 11 individuals with mild cognitive impairment (MCI). Subjects were cognitively assessed by the Mini-Mental State Examination (MMSE) and the CAMDEX schedule. Platelet PLA₂ activity was determined by radio-enzymatic assay, which mainly detected a calcium-independent form of the enzyme present also in the brain (iPLA₂). PLA₂ activity was significantly lower in AD than in controls (p<0.001). Mean PLA₂ activity in MCI individuals was between the values of AD patients and controls, with a subgroup showing PLA as low as the lowest AD patients, but the differences from MCI were not significant from AD and control groups. Lower PLA₂ activity was significantly correlated with a worse cognitive performance both at the MMSE (p=0.001) and the cognitive sub-scale of the CAMDEX inventory (p=0.002). Our data replicate previous findings of reduced platelet PLA₂ activity in AD. Both reduced PLA₂ activity and the correlation with impaired cognition were also reported in brain tissue of AD patients, suggesting thus that the present determinations in platelets may be related to a reduction in the brain. In the brain the inhibition of PLA₂ inhibits the physiological secretion of the APP, a mechanism that increases A formation. Further longitudinal studies should investigate whether those MCI individuals with the lowest PLA₂ values in platelets would be at a higher risk to develop AD during a longitudinal follow up.     

CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45<Superscript>high</Superscript>CD11b<Superscript>+</Superscript> monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease

CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler's murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease.     

Increased T-cell Reactivity and Elevated Levels of CD8<Superscript>+</Superscript> Memory T-cells in Alzheimer’s Disease-patients and T-cell Hyporeactivity in an Alzheimer’s Disease-mouse Model: Implications for Immunotherapy

Neuroinflammation is observed in neurodegenerative diseases like Alzheimer’s disease (AD). However, a little is known about the mechanisms of neural-immune interactions. The involvement of peripheral T-cell function in AD is still far from clear, though it plays an important role in immunotherapy. The aim of this study was to determine peripheral T-cell reactivity in AD patients and in an AD mouse model. Mitogenic activation via ligation of the T-cell receptor (TCR) with PHA-L was measured in T lymphocytes from AD patients and Thy1(APP_751SL) × HMG(PS1_M146L)-transgenic mice (APP × PS1). In order to uncover failures in TCR signaling, the TCR was also bypassed by PMA and ionomycin treatment. All patients were sporadic late onset cases and the transgenic mice expressed no mutant APP in lymphocytes, so that direct interactions of mutant APP on T-cell function can be excluded. CD4⁺ and CD8⁺ T-cell showed increased reactivity (tyrosine phosphorylation, CD69 expression, and proliferation) in AD, while APP × PS1 transgenic mice displayed hyporeactive CD8⁺ T-cells after TCR ligation. Increased levels of CD8⁺ T memory cells and down regulation of CD8 receptor were found in AD and the animal model. Anergic TCR uncoupling was associated with loss of MAPK signaling (p38, ERK1 and ERK2) in APP × PS1. Our data implicate the generation of reactive memory T-cell in AD and of anergic memory T-cells in transgenic mice and should be taken into concern when designing immunotherapy.     

The BDNF Val<Superscript>66</Superscript>Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease

Parkinson’s disease (PD) patients show a range of cognitive deficits,which may relate to abnormalities in dopaminergic transmission in fronto–striatal circuitry. In this study, we have investigated the impact of brainderived neurotrophic factor (BDNF) val⁶⁶met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. This polymorphism significantly influences BDNF secretion in the CNS, and BDNF is known to influence dopaminergic neurons and cognitive processes. Patients with PD totalling 291 who had undergone detailed motor and cognitive assessments as part of a population–based study of PD were genotyped for the BDNF val⁶⁶met polymorphism. The impact of this polymorphism on cognitive ability was determined using multivariate analysis to adjust for possible confounding variables. Patients with low rates of BDNF secretion (met alleles) performed significantly better at the TOL task than those with high rates of secretion (val alleles). Furthermore, subgroup analyses revealed that the effect is most apparent in women and among patients with prior dopaminergic exposure. We speculate that BDNF may interact with dopaminergic transmission and dopamine receptor stimulation in the frontostriatal circuitry, with subsequent consequences on cognition in Parkinson’s disease.     

Sleep microstructure and neurodegeneration as measured by [<Superscript>123</Superscript>I]β-CIT SPECT in treated patients with Parkinson’s disease

Abstract Objectives Along with spindles, K-complexes are well known hallmarks of stage 2 (S2) sleep. However, little is known about their quantity in S2 sleep of patients with Parkinsons disease (PD). Setting Sleep laboratory, Department of Neurology, University of Vienna, Austria. Patients and methods Whole-night polysomnography (PSG) was performed in twelve treated PD patients and ten healthy controls without history of sleep complaints. The quantity of spontaneous K-complexes, K-alpha-complexes, and sleep spindles in one hour S2 sleep, distributed in four epochs of 15 minutes all through the night, were visually selected and analysed. The quantity and the temporal course of these phasic events were compared with the quantity in age-matched healthy controls. Nine of the twelve PD patients underwent [¹²³I]-CIT SPECT for calculating dopamine transporter binding in the striatum and serotonin transporter density in the thalamus-hypothalamus region. Results There was no difference between the quantity of K-complexes, K-alpha-complexes, and sleep spindles in PD patients and in the healthy control group. K-complexes but not sleep spindles decreased over the night in both groups. The number of sleep spindles did not correlate with the dopamine transporter binding in the striatum or the serotonin binding in the thalamic/hypothalamic region. Conclusion K-complexes and sleep spindles are not reduced and do not seem to be related to the degree of dopaminergic degeneration in treated PD patients.This research was supported in part by the European Commission, DG XII (Project Biomed-2 BMH4-CT97–2040 SIESTA) and by the Austrian National Bank (Project 7870). Svenja Happe, MD, was recipient for a fellowship stipend of the European Neurological Society (ENS).     

Blockage of the Action of the Proneurotoxin MPTP and Toxin MPP<Superscript>+</Superscript> by Extracts of Homogenates of <Emphasis Type="Italic">Alphitobius diaperinus</Emphasis> Litter Beetles in an Experimental Model of Parkinson’s Disease

Adult male mice C57BL/6 (n = 105) were divided into five groups. The first group served as a control. In the 2nd–5th groups, the animals were treated subcutaneously with 40 mg/kg of proneurotoxin MPTP (methylphenyltetrahydropyridine), which forms a state similar to the initial stage of Parkinson’s disease over a 2-week period. Mice of groups 3–5 daily received an additive along with their food: one of three extracts of the biomass of the litter beetle Alphitobius diaperinus. In 2 weeks, all animals were tested for motor disorders in the vertical bar test; they were then euthanized and histochemical analysis of the dopamine-containing brain regions was performed. In addition, the same extracts were tested for counteraction to MPP⁺ toxin in cultured neuroblastoma cells. It was found that the primary aqueous and, especially, secondary water–methanol extracts had a powerful protective effect against the neurotoxic effect judging by the results of both the behavioral test and morphological control. Arginine was found at substantial concentrations in both effective extracts. An in vitro study confirmed the protective effect of the primary aqueous extract.