The effect of orexin-A on motor and cognitive functions in a rat model of Parkinson’s disease

Objective: The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson’s disease. Methods: Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests. Cognitive function was assessed by passive avoidance test (Shuttle box). Results: OX-A administration in 6-OHDA treated rats remarkably increased the time which animals run on rod (in rotarod test) and also the latency to fall (in hanging test) (P < 0.01 and P < 0.001, respectively). Conversely, administration of SB in 6-OHDA-treated rats decreased the mentioned indices (P < 0.05 for latency to fall). Administration of agonist and/or antagonist of orexin-1 receptors had no significant effect on 6-OHDA induced cognitive impairment in rats. Conclusion: Results of this study suggest that the orexinergic system might be involved in sensory-motor deficits of Parkinson’s disease.     

The impact of loneliness and social isolation on the development of cognitive decline and Alzheimer’s Disease

Alzheimer’s Disease (AD) is the leading cause of dementia, observed at a higher incidence in women compared with men. Treatments aimed at improving pathology in AD remain ineffective to stop disease progression. This makes the detection of the early intervention strategies to reduce future disease risk extremely important. Isolation and loneliness have been identified among the major risk factors for AD. The increasing prevalence of both loneliness and AD emphasizes the urgent need to understand this association to inform treatment. Here we present a comprehensive review of both clinical and preclinical studies that investigated loneliness and social isolation as risk factors for AD. We discuss that understanding the mechanisms of how loneliness exacerbates cognitive impairment and AD with a focus on sex differences will shed the light for the underlying mechanisms regarding loneliness as a risk factor for AD and to develop effective prevention or treatment strategies.     

The effect of real and virtual visual cues on walking in Parkinson’s disease

Patients with Parkinson’s disease (PwPD) have a slow, shuffling gait, marked by sporadic freezing of gait (FoG) during which effective stepping ceases temporarily. As these gait problems are not commonly improved by medical and surgical treatments, alternative approaches to manage these problems have been adopted. The aim of this study was to evaluate the effect of real and virtual visual cues on walking in PD. We assessed 26 mid-stage PwPD, on and off medication, on a laboratory-based walking task which simulated real world challenges by incorporating FoG triggers and using appropriate placebo conditions. Cueing interventions were presented via virtual reality glasses (VRG rhythmic, visual flow and static placebo cues), and as transverse lines (TL) on the walkway. Objective measures of gait (task completion time; velocity, cadence, stride length; FoG frequency) and self-rated fear of falling (FoF) were recorded. Cueing intervention affected task completion time only off medication. Whereas placebo VRG cues provided no improvement in walking, visual flow VRG cues marginally reduced the task completion time. TL on the floor elicited more substantial improvements in gait with reduced cadence, increased stride length and reduced FoG frequency. VRG rhythmic cueing impaired overall walking. Notably, a final no-intervention condition yielded quicker task completion, greater walking velocity, increased stride length and less frequent FoG. Although the VRG produced modest improvements only in the visual flow condition, their flexibility is an advantage. These results endorse the use of TL and justify further testing and customisation of VRG cues for individual PwPD.     

Mitochondria in the context of Parkinson’s disease

<正>Introduction to the disease:Parkinson’s disease(PD)is the second most common neurodegenerative disease,affecting 1–2%of the population over the age of 65.Rigidity,bradikynesia,postural instability and tremor are the principal clinical characteristics of this disease,     

The effect of Parkinson’s disease subgroups on verbal and nonverbal fluency

Background. Parkinson’s disease (PD) leads to deficits in executive function, including verbal and nonverbal fluency, as a result of compromised frontostriatal circuits. It is unknown whether deficits in verbal and nonverbal fluency in PD are driven by certain subgroups of patients, or how strategy use may facilitate performance. Participants. Sixty-five nondemented individuals with PD, including 36 with right-body onset (RPD; 20 with tremor as their initial symptom, 16 nontremor) and 29 with left-body onset (LPD; 14 with tremor as their initial symptom, 15 nontremor), and 52 normal control participants (NC) took part in the study. Measurements. Verbal fluency was assessed using the FAS and Animals tests. Nonverbal fluency was assessed using the Ruff Figural Fluency Test. Results. Both RPD and LPD were impaired in generating words and in using clustering and switching strategies on phonemic verbal fluency, whereas different patterns of impairment were found on nonverbal fluency depending on the interaction of side of onset and initial motor symptom (tremor vs. nontremor). Strategy use correlated with number of correct responses on verbal fluency in LPD, RPD, and NC. By contrast, on nonverbal fluency, strategy use correlated with correct responses for RPD and LPD, but not for NC. Conclusion. Our findings demonstrate the importance of considering subgroups in PD and analyzing subcomponents of verbal and nonverbal fluency (correct responses, errors, and strategies), which may depend differently on the integrity of dorsolateral prefrontal cortex, inferior frontal cortex, and anterior cingulate cortex.     

The neuroprotective effect of two statins: simvastatin and pravastatin on a streptozotocin-induced model of Alzheimer’s disease in rats

Astrocytes play a fundamental role in glutamate metabolism by regulating the extracellular levels of glutamate and intracellular levels of glutamine. They also participate in antioxidant defenses, due to the synthesis of glutathione, coupled to glutamate metabolism. Although the cause of Alzheimer’s disease (AD) remains elusive, some changes in neurochemical parameters, such as glutamate uptake, glutamine synthetase activity and glutathione have been investigated in this disease. A possible neuroprotective effect of two statins, simvastatin and pravastatin (administered p.o.), was evaluated using a model of dementia, based on the intracerebroventricular (ICV) administration of streptozotocin (STZ), and astrocyte parameters were determined. We confirmed a cognitive deficit in rats submitted to ICV-STZ, and a prevention of this deficit by statin administration. Moreover, both statins were able to prevent the decrease in glutathione content and glutamine synthetase activity in this model of AD. Interestingly, simvastatin increased per se glutamate uptake activity, while both statins increased glutamine synthetase activity per se. These results support the idea that these drugs could be effective for the prevention of alterations observed in the STZ dementia model and may contribute to reduce the cognitive impairment and brain damage observed in AD patients.     

Inhibitory effect of oxytocin on corticotrope function in humans: are vasopressin and oxytocin ying-yang neurohormones?

Oxytocin (OT) and vasopressin (VP) are very similar neurohypophyseal peptides. While VP is known as an ACTH stimulating factor synergistic to CRF since two decades, the inhibiting activity of OT, first demonstrated in the human, is now confirmed in various species including mouse and rat!It is likely that endogenous oxytocinergic system which can be activated by physiological and/or pharmacological manipulation can "buffer" the stress activated vasopressin-ACTH-cortisol action.Since VP and OT share also opposite action on cognitive function, those two "sister" neuropeptides might be considered as "ago-antagonist" or "ying-yang" neurohormones!     

The neuroprotective effect of dental pulp cells in models of Alzheimer’s and Parkinson’s disease

Aim of the present study was to investigate the neuroprotective effect of dental pulp cells (DPCs) in in vitro models of Alzheimer and Parkinson disease. Primary cultures of hippocampal and ventral mesencephalic neurons were treated for 24 h with amyloid beta (Aβ_1–42) peptide 1–42 and 6-OHDA, respectively. DPCs isolated from adult rat incisors were previously cultured in tissue culture inserts and added to the neuron cultures 2 days prior to neurotoxin treatment. Cell viability was assessed by the MTT assay. The co-culture with DPCs significantly attenuated 6-OHDA and Aβ_1–42-induced toxicity in primary cultures of mesencephalic and hippocampal neurons, and lead to an increase in neuronal viability in untreated cultures, suggesting a neurotrophic effect in both models. Furthermore, human dental pulp cells expressed a neuronal phenotype and produced the neurotrophic factors NGF, GDNF, BDNF, and BMP2 shown by microarray screening and antibody staining for the representative proteins. DPCs protected primary neurons in in vitro models of Alzheimer’s and Parkinson’s disease and can be viewed as possible candidates for studies on cell-based therapy. C. Apel and O. V. Forlenza: both authors contributed equally to the work.     

How does the ‘environment’ come to the person? The ‘ecology of the person’ and addiction

Currently, psychiatry lacks a field that can be called “theoretical psychiatry”, which uses theoretical concepts and explanatory models: The main stream of research is to collect data of all kinds in the hope that the computational Big Data approach will shed a bright light on the black box of mental disorders. Accordingly, the biology-based Research Domain Criteria of the National Institute of Mental Health have been established. However, as philosophical analyses of concepts and methods have shown, several epistemological gaps stand in the way of a consistent multilevel understanding of mental disorders. Also, the implicit ontological problems in the biological reduction of the psychosocial level and in the integration of so-called hard and soft disciplines are mostly left out. As a consequence, a non-reductive psychological theory of mental disorders is sought that also integrates correlating biological and sociological issues. In this context, one example of promising nonreductive psychiatric research is the option of systems/network psychopathology. The possibilities for integrating different psychological perspectives are highlighted for the field of addiction research and treatment, where pragmatic behaviorist approaches dominate over the theory-based practice of psychoanalysis. In comparing the theoretical constructs of these two approaches, the relevance of the concept of “(social) environment” as the wealth of influential sociocultural factors is discussed at levels superior to the interpersonal micro-level, namely the organizational meso- and societal macro level, which is not sufficiently considered in current biopsychiatry. On this basis of argumentation, the usefulness of grounding and framing psychiatry through the field of ecological sciences, especially human ecology, is demonstrated. Finally, to this end, an outline of an ecological model of mental health and illness is presented.     

Central distribution of oxytocin and vasopressin 1a receptors in juvenile Richardson’s ground squirrels

Oxytocin and vasopressin are well-conserved peptides important to the regulation of numerous aspects of social behavior, including sociality. Research exploring the distribution of the receptors for oxytocin (Oxtr) and for vasopressin (Avpr1a) in mammals has revealed associations between receptor distribution, sociality, and species’ mating systems. Given that sociality and gregariousness can be tightly linked to reproduction, these nonapeptides unsurprisingly support affiliative behaviors that are important for mating and offspring care. We localized these receptors in juvenile Richardson’s ground squirrel brains to determine whether distribution patterns of Oxtr and Avpr1a that are associated with promiscuous mating systems differ in rodents that also exhibit non-reproductive affiliation. These squirrels are social, colonial, and engage in nepotistic alarm calling behavior and affiliation outside of a reproductive context. Juveniles are the most affiliative age-class and are non-reproductive; making them ideal for examining these associations. We found that juveniles had dense Oxtr binding in the dentate gyrus of the hippocampus, amygdala, lateral septum, bed nucleus of the stria terminalis and medial geniculate nucleus. Juveniles had low to modest levels of Avpr1a binding in the medial preoptic area, olfactory bulbs, nucleus accumbens, superior colliculus, and inferior colliculus. We noted Oxtr and Avpr1a binding in the social behavior neural network (SBNN), further supporting a role of these nonapeptides in modulating social behavior across taxa. Oxtr and Avpr1a binding was also present in brain regions important to auditory processing that have known projections to the SBNN. We speculate that these neural substrates may be where these nonapeptides regulate communication.     

The effect of dopamine replacement therapy on haptic sensitivity in Parkinson’s disease

Increasing evidence indicates that processing of proprioceptive information is altered in Parkinson’s disease (PD), leading to reduced kinaesthetic and haptic sensitivity. However, there is inconclusive evidence whether dopamine replacement therapy (DRT) ameliorates or worsens kinaesthetic and haptic function in PD. For assessing perceptual function, we employed a task that did not require active motion or stressed working memory function, which may become impaired in PD. A group of mild to moderate stage PD patients (n = 9) and a group of age-matched healthy controls participated in this study. Without vision, a subject’s hand was moved by a robotic manipulandum along the contours of a small “virtual box” (5 × 15 cm). At the end of each trial, they indicated whether the contour was “curved” or “straight”. PD patients were tested ON and OFF antiparkinsonian medication. Psychophysical detection thresholds were determined (curvature at which subjects correctly perceived a curved contour at the 75% level). Compared to the control group, thresholds were elevated by 55% in the PD patient group. During the ON medication state, the mean detection threshold of the patient group was reduced by 15% (ON: 4.71 m⁻¹; OFF: 5.42 m⁻¹). Increases in curvature sensitivity were highly correlated with improved clinical scores of motor function (r = 0.74) with more affected patients showing higher gains in sensitivity as the result of DRT (r = 0.80). This report documents that DRT can ameliorate haptic and kinaesthetic function in patients with mild to moderate PD, suggesting that DRT can have beneficial effects on perceptual function.     

Short-chain fatty acids in the context of Parkinson’s disease

Research on neurodegenerative diseases such as Alzheimer’s disease,Parkinson′s disease(PD),Huntington’s disease or amyotrophic lateral sclerosis is becoming increasingly important in our society.Due to the ageing of the population,the prevalence of these diseases continue to rise worldwide,and causal cures are not yet available(Erkkinen et al.,2018).This Perspective focusses on PD,a movement disorder of the central nervous system with an estimated prevalence between 65 and 1250/100,000 in Europe,affecting about 1 percent of the population older than 60 years.The clinical symptoms include motor symptoms like bradykinesia,tremor or rigidity which are associated with loss of dopaminergic neurons in the substantia nigra and their innervating axonal fibers to the striatum.Additional non-motor symptoms may consist in depression,hyposmia,cognitive decline or constipation due to impaired motility of the gastrointestinal tract.     

Prognostic value of Alzheimer’s biomarkers in mild cognitive impairment: the effect of age at onset

Journal of Neurology - The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive...     

The proinflammatory effect of C-reactive protein on human endothelial cells depends on the FcγRIIa genotype

Introduction

The stimulatory effects of CRP (C-reactive protein) on endothelial cells are mainly mediated via FcγRIIa. This receptor exists in two different allotypes bearing either arginine (R131) or histidine (H131) at the extracellular amino acid position 131 of the mature protein, but only FcγRIIa-R131 displays high avidity for CRP. This study investigated the role of the FcγRIIa genotype in CRP-stimulated endothelial cells.

Materials and Methods

We tested the effects of CRP on expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the endothelial release of pro-inflammatory molecules as a function of the FcγRIIa-genotype (FcγRIIa-H/H131, FcγRIIa-H/R131, FcγRIIa-R/R131) in HUVEC (Human Umbilical Vein Endothelial Cells). HUVEC were grouped according to their FcγRIIa status by genotyping with an allele specific nested-PCR. The expression of ICAM-1, VCAM-1, and E-selectin on HUVEC was detected by flow cytometry. The release of soluble markers (sCD40L, IL-6, IL-8, MCP-1, tPA, sP-selectin, and sVCAM-1) was measured using a multiplex assay for flow cytometry.

Results and Conclusions

CRP-stimulated expression of ICAM-1 and E-selectin was dependent on the specific FcγRIIa-genotype, with most pronounced induction in HUVEC with the FcγRIIa-R/R genotype, followed by H/R and H/H. In accordance with this finding, the supernatants of stimulated HUVEC with the R/R genotype showed significantly higher levels of tPA, MCP-1, and IL-6.Our data show that CRP stimulates the expression of adhesion molecules and the release of soluble markers by HUVEC as a function of the FcγRIIa-genotype. These findings could be relevant in the context of risk stratification in patients with cardiovascular disease.     

The effect of l-Dopa administration on pursuit ocular movements in suspected Parkinson’s disease

The objective of this study is to evaluate pursuit ocular movements (POM) by using a vision-based non-intrusive eye tracker, in patients with suspected Parkinson’s disease (PD), before and after l-Dopa administration. We studied ten patients with suspected diagnosis of idiopathic PD. We compared POM values to those of a group of normal controls (NC), and evaluated them before and after l-Dopa administration. Unified Parkinson’s Disease Rating Scale (UPDRS) motor subscores improved significantly (p = 0.001). At baseline, values of POM were lower in suspected PD patients than in NC (p = 0.01). One hour after l-Dopa administration, POM values correlated with UPDRS motor subscore (p = 0.01). We used a recent method, a new vision-based non-intrusive eye tracker, previously described, which can be proposed as a possible tool for supporting the diagnosis of PD in association with levodopa test, as an add-on to the UPDRS score.     

The effect of Daicong solution on hippocampal muscarinic receptors 1 and 3 gene expression in a rat model of Alzheimer’s disease*☆

BACKGROUND： It has been previously shown that the muscarinic （M） receptor is involved in brain arousal and selective attention, mood, and motor coordination.
OBJECTIVE： To explore the effects of various intragastric Daicong doses on hippocampal MI and M3 receptor gene expression in a rat model of Alzheimer＇s disease.
DESIGN, TIME AND SETTING： A randomized cellular and molecular biology experiment, conducted at the Molecular Immunology Laboratory in Shandong between October 2006 and April 2007.
MATERIALS： Fifty 22-month old Sprague Dawley rats, weighing 250-300 g were used for this experiment. Kainic acid was used to lesion the nucleus basalis to establish a rat model of Alzheimer＇s disease. The components of Daicong solution were as follows： ginseng, rehmannia dride rhizome, anemarrhena, and radix astragali. The solution was provided by the Affiliated Hospital to Weifang Medical College, according to preparation techniques of extracting liquid for traditional Chinese medicine （1 g crude drug/mL solution）. Kainic acid was provided by Professor Xiuyan Li at Weifang Medical College.
METHODS： The rats were randomly divided into 5 groups, 10 rats in each group. Four groups were used for model establishment, and the fifth group served as a normal control group. Three of the model groups were intragastrically administered 5, 10, and 20 g/kg/d Daicong solution, and an additional model group and normal control group received normal saline （10 mL/kg/d）. Drugs were administered over a time period of one month.
MAIN OUTCOME MEASURES： Four days after model establishment, Morris water maze was used to measure learning and memory capabilities. RT-PCR was used to detect the effect of Daicong solution on mRNA expression of M1 and M3 receptor in the hippocampus of all groups. RESULTS： Fifty rats were included in the final analysis, without any loss. M1 and M3 receptor mRNA expression was decreased in the model group, compared to the normal control group （P 〈 0.05）. Upon Daicong admin     

The effect of maternal migraine headache on their children’s quality of life

Migraine is an episodic disease characterized by a throbbing and generally unilateral headache, often accompanied by nausea, vomiting and light and sound sensitivity. Migraine is known to affect one’s quality of life; not only the person with migraine but also his/her family and social environment are affected by this condition. Our study aimed to evaluate the effects of maternal migraine on children’s quality of life. The patient group comprised 70 mothers with migraine diagnoses and their 111 healthy children, while 50 healthy mothers and their 86 children were included in this study as the control group. The Visual Analog Scale (VAS), Migraine Disability Assessment Scale, Beck Depression Index (BDI) and Beck Anxiety Index (BAI) were used for evaluation of mothers; 3 to 7-year old KINDL and 7- to 17-year-old KINDL-R Quality of Life Scales were used to evaluate the quality of life of children. The SPSS 21.0 program was used for statistical analysis and p < 0.05 was assumed to be statistically significant. The mean age of the migraine group was 37.09 ± 6.94 years, and the mean age of the control group was 38.2 ± 4.5. Symptoms of depression and anxiety were more frequently found in subjects with migraine (p < 0.05). In comparison with the control group: 3 to 7-year old KINDL total scores, self-esteem and school subscales, 7- to 17-year-old KINDL total scores, self-esteem and the social relationships subscale scores were lower in migraine group. It was found to be significant that VAS, BDI and BAI scores of the mothers were negatively correlated with the children’s quality of life. Our study concluded that the presence of migraine-type headache in mothers worsen the relations in school, self-esteem and quality of life in younger children and social relations, relations in school and quality of life in older children. The maternal age, disease severity, and anxiety and depression symptoms were shown to predict the quality of life in children. Performing preventive interventions by individually assessing bio-psycho-social elements for the treatment of mothers with migraine will preserve other family member’s and especially children’s quality of life.     

Cochrane’s risk of bias tool in the context of psychotherapy outcome research

The Cochrane risk of bias tool (RoB) is a widely used measure for methodological quality of randomized controlled trials. This paper discusses RoB’s rationale and risk of bias domains, reports on its application in current psychotherapy meta-analyses, and offers comments regarding the application of RoB in the context of psychotherapy outcome research. Our suggestions include focusing on patient’s and therapist’s expectations when judging the domain “blinding of personnel and participants” and paying greater attention to the domain “selective outcome reporting” and to matters of “treatment implementation.”

Clinical or methodological significance of this article: This paper discusses the rationale of a widely used tool to assess the methodological quality of primary studies for meta-analysis and provides suggestions for its use in the context of psychotherapy outcome research.