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Current evidence has shown that exercise can reduce symptoms of Parkinson's disease (PD). However, previous studies indicated mixed results, possibly because of variability in terms of the nature of the exercise interventions. The purpose of this study was to perform a metaanalysis of current evidence from endurance exercise intervention studies for effects on the United Parkinson's Disease Rating Scale (UPDRS) in individuals with PD. A systematic literature search in six electronic databases was performed and two independent reviewers screened the title and abstract of 1106 records captured by the initial search. Inclusion criteria for full-text review were (A) peer-reviewed English-language publications, (B) randomized controlled trials that compared an endurance exercise intervention group to a non-exercising control group, and (C) an outcome measure which included the UPDRS total score or section III (motor) subscore. From the title/abstract screening, the same independent reviewers assessed 245 full-text articles for eligibility. Of the fulltext articles reviewed 7 articles were included in our meta-analysis, 238 were excluded for the following reasons: 147 did not meet endurance exercise criteria, 53 were review/systematic reviews, 34 were conference abstracts or posters, 2 were editorial or commentary, 1 was a study protocol, and 1 was unpublished. The d index was used to calculate the difference between means of different groups within individual studies, and a weighting factor or w was used to calculate the effect size across studies. Overall, d index was found to be -0.32 with 95% confidence interval, CI (-0.09, -0.56) found to be statistically significant indicating a positive effect of endurance exercise in UPDRS scores. In conclusion, this meta-analysis supports integrating endurance exercise training, as defined by ACSM, into treatment of PD.

The midbrain dopaminergic perikarya are differentially affected in Parkinson’s disease (PD). This study compared the effects of a partial unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion model of PD on the number, morphology, and nucleolar volume of dopaminergic cells in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and retrorubral field (RRF). Adult, male rats (n=10) underwent unilateral intrastriatal infusion of 6-OHDA (12.5 μg). Lesions were verified by amphetamine-stimulated rotation 7 days post-infusion. Rats were euthanized 14 days after treatment with 6-OHDA and brains were stained with a tyrosine hydroxylase-silver nucleolar (TH-AgNOR) stain. Dopaminergic cell number and morphology in the lesioned and intact hemispheres were quantified using stereological methods. The magnitude of decrease in planimetric volume, neuronal number, cell density, and neuronal volume resulting from 6-OHDA lesion differed between regions, with the SNpc exhibiting the greatest loss of neurons (46%), but the smallest decrease in neuronal volume (13%). The lesion also resulted in a decrease in nucleolar volume that was similar in all three regions (22–26%). These findings indicate that intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the SNpc, VTA, and RRF; however, the resulting changes in nucleolar morphology suggest a similar cellular response to the toxin in all three cell populations.

Chronic alcohol exposure-induced changes in reinforcement mechanisms and motivational state are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Here we describe the long-lasting alterations of γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc after chronic intermittent ethanol (CIE) treatment, a rat model of alcohol dependence. CIE treatment and withdrawal (>40 days) produced decreases in the ethanol and Ro15-4513 potentiation of extrasynaptic GABAARs, which mediate the picrotoxin-sensitive tonic current ( Itonic), while potentiation of synaptic receptors, which give rise to miniature inhibitory postsynaptic currents (mIPSCs), was increased. Diazepam sensitivity of both Itonicand mIPSCs was decreased by CIE treatment. The average magnitude of Itonicwas unchanged, but mIPSC amplitude and frequency decreased and mIPSC rise time increased after CIE treatment. Rise-time histograms revealed decreased frequency of fast-rising mIPSCs after CIE treatment, consistent with possible decreases in somatic GABAergic synapses in MSNs from CIE rats. However, unbiased stereological analysis of NeuN-stained NAcc neurons did not detect any decreases in NAcc volume, neuronal numbers, or neuronal cell body volume. Western blot analysis of surface subunit levels revealed selective decreases in α1 and δ and increases in α4, α5, and γ2 GABAAR subunits after CIE treatment and withdrawal. Similar, but reversible, alterations occurred after a single ethanol dose (5 g/kg). These data reveal CIE-induced long-lasting neuroadaptations in the NAcc GABAergic neurotransmission.

Neurotoxic lesions of the nigrostriatal pathway model the deficits found in Parkinson’s disease. This study used stereology and a novel staining method to examine the effects of a partial unilateral striatal 6-hydroxydopamine (6-OHDA) lesion on substantia nigra pars compacta (SNpc) dopamine neuron number and morphology in rats. Adult male Long-Evans rats were subjected to unilateral lesion of the SNpc by intrastriatal microinjection of 6-OHDA (12.5 μg). Lesions were verified by d-amphetamine-stimulated rotation (2.5 mg/kg, sc) by force-plate rotometry 7 days post-surgery. Seven days after rotation testing, rats were euthanized, and brains were prepared for either histology (n = 12) or determination of striatal dopamine content by HPLC-EC (n =20). Brains prepared for histology were stained for tyrosine hydroxylase (TH) combined with a silver nucleolar stain (AgNOR) using a modified protocol developed for stereological assessment. The AgNOR counterstain allowed for precise definition of the nucleolus of the cells, facilitating both counting and qualitative morphometry of TH-positive neurons. Stereological quantitation determined a 54% decrease in TH-positive neuron number (P

The protective impact of exercise on neurodegenerative processes has not been confirmed, and the mechanisms underlying the benefit of exercise have not been determined in human Parkinson’s disease or in chronic animal disease models. This research examined the long-term neurological, behavioral, and mechanistic consequences of endurance exercise in experimental chronic parkinsonism. We used a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease with moderate neurodegeneration and examined the effects of treadmill exercise on movement and balance coordination, changes in dopamine neuron biomarkers, mitochondrial functions, and neurotrophic factor activities in the nigrostriatal system. The exercise results were compared with that of the control and sedentary chronic parkinsonian animals. After 18 weeks of exercise training in the chronic parkinsonian mice, we observed a significant deterrence in the loss of neuronal dopamine-producing cells and other functional indicators. The impaired movement and balance incoordination in the chronic parkinsonian mice were also markedly reduced following exercise. Mechanistic investigations revealed that the neuronal and behavioral recovery produced by exercise in the chronic parkinsonian mice was associated with an improved mitochondrial function and an increase in the brain region-specific levels of brain-derived and glial cell line-derived neurotrophic factors. Our findings indicate that exercise not only produces neuronal and mitochondrial protection, it also boosts nigrostriatal neurotrophic factor levels in the chronic parkinsonian mice with moderate neurodegeneration. Therefore, modifying lifestyle with increased exercise activity would be a non-pharmacological neuroprotective approach for averting neurodegenerative processes, as demonstrated in experimental chronic parkinsonism.

Chemokine (C-C motif) ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, plays a critical role in leukocyte recruitment and activation. In the present study, we identify an additional role for CCL2 that of neuroprotection against HIV-1 transactivator protein (Tat) toxicity in rat primary midbrain neurons. Furthermore, we report the involvement of transient receptor potential canonical (TRPC) channels in CCL2-mediated neuroprotection. TRPC are Ca2+-permeable, nonselective cation channels with a variety of physiological functions. Blockage of TRPC channels resulted in suppression of both CCL2-mediated neuroprotection and intracellular Ca2+elevations. Parallel but distinct extracellular signal-regulated kinase (ERK)/cAMP response element-binding protein (CREB) and Akt/nuclear factor κB (NF-κB) pathways were involved in the CCL2-mediated neuroprotection. Blocking TRPC channels and specific downregulation of TRPC channels 1 and 5 resulted in suppression of CCL2-induced ERK/CREB activation but not Akt/NF-κB activation.In vivorelevance of these findings was further corroborated in wild-type and CCR2 knock-out mice. In the wild-type but not CCR2 knock-out mice, exogenous CCL2 exerted neuroprotection against intrastriatal injection of HIV-1 Tat. These findings clearly demonstrate a novel role of TRPC channels in the protection of neurons against Tat through the CCL2/CCR2 axis.

Loss of dopaminergic neurons in the substantia nigra (A9 cells) and ventral tegmental area (VTA) (A10 cells) has been reported in Parkinson's disease with reference to causing motor and non-motor deficits, although clinical and laboratory animal studies on the degeneration of VTA neurons are less emphasized comparative to the degeneration of substantia nigra neurons. In the present study, we examined the VTA dopaminergic neurons in a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid at a level showing moderate neurodegeneration and studied the impact of endurance exercise on VTA neurons in this model. In comparison to the normal control animals, the chronic mouse model of Parkinson's disease with moderate neurodegeneration demonstrated a significant reduction of VTA neurons (52% loss), when these animals were kept sedentary throughout the study. Morphologically, the VTA dopaminergic neurons in this model displayed a decrease in cell volume and showed irregular or disparaging axonal and dendritic projections. When the chronic Parkinsonian mice were exercised on a motorized rodent treadmill up to 15 m/min, 40 min/day, 5 days/week for 10 and 18 weeks, the total number of VTA dopaminergic neurons were significantly higher than the sedentary Parkinsonian animals. Especially noted with the 18-week exercised Parkinsonian mice, the number of VTA neurons returned to normal range and the cells were densely populated and displayed distinctive axons and dendritic arborization. These results demonstrate that prolonged exercise training is neuroprotective to the dopaminergic neurons in the VTA of the chronic mouse model of Parkinson's disease with moderate neurodegeneration.

The structures and circuits of the central and the peripheral nervous systems provide the basis for thinking, speaking, experiencing sensations, and performing perceptual and motor activities in daily life. Healthy people experience normal functioning without giving brain functions a second thought, while dysfunction of the neural circuits may lead to marked impairments in cognition, communication, sensory awareness, and performing perceptual and motor tasks. Neuroscience literacy provides the knowledge to associate the deficits observed in patients with the underlying deficits in the structures and circuits of the nervous system. The purpose of this paper is to begin the conversation in this area via a neuroscience literacy model of "Brain Tells," defined as stereotypical or observable behaviors often associated with brain dysfunction. Occupational therapists and other allied health professionals should be alert for the signs of "Brain Tells" that may be early warning signs of brain pathology. We also suggest that neuroscience literacy be emphasized in training provided to public safety workers, teachers, caregivers, and health care professionals at all levels.

Parkinson's disease (PD) profoundly affects activities of daily living (ADL) and quality of human life. Although unilateral pallidotomy has become a common surgical treatment for persons with advanced PD, functional outcome data from previous reports have failed to uniformly support this procedure. In the present investigation, results from 12 studies meeting specific inclusion criteria were subjected to meta-analysis. Only reports featuring unilateral pallidotomy as the exclusive surgery, a sample size of at least five patients, explicit assessment of ADL, and sufficient quantitative data were subjected to analysis. Type of research design was not a factor in the selection process. The results of our analysis suggest that unilateral pallidotomy successfully enhances functional outcome in patients with clinically advanced PD.

Growing concern about science literacy in the United States has led to the active involvement of scientists in educational reform. Yet scientists have often found it difficult to communicate content knowledge in an effective manner to both teachers and children. This model project, funded by the National Institute of Drug Abuse, has been aimed at increasing the awareness and understanding of neuroscience among elementary school children to indirectly decrease drug use and unhealthy behaviors. The project created a partnership between neuroscientists, health professionals, and the Boys and Girls Clubs of Omaha, Nebraska, to present hands-on activities about basic and applied aspects of the nervous system in a “reverse” science fair setting. Neuroscientists and health professionals created hands-on, interactive exhibits that the children judged. This particular study examined the perceptions of neuroscientists and allied health professionals regarding their ability to communicate neuroscience knowledge to school-age children and their understanding of the knowledge and interest of children about neuroscience in relation to children’s self-reports of knowledge and interest in neuroscience. Participation in a fair significantly raised professionals’ perceptions of their ability to communicate science content to fourth- and sixth-grade children. There was considerable discrepancy between the professionals’ assessment of what children know, and want to know, about neuroscience, and what the children do know and want to know about the nervous system. After observing children engaging in neuroscience activities, many presenters rated children’s interest levels in neuroscience and in their projects considerably higher than before. Presenting neuroscience concepts to the children was thus less difficult than the professionals had perceived prior to the fair. The reverse science fair approach is one way to foster the involvement of neuroscientists and health professionals in increasing knowledge transfer, and neuroscience literacy, in the formative childhood years.

This study was aimed at understanding the current physical and occupational therapy practices in stroke rehabilitation in the Midwest. The insights gained from this pilot study will be used in a future study aimed at understanding stroke rehabilitation practices across the nation. Researchers and clinicians in the field of stroke rehabilitation were interviewed, and past studies in the literature were analyzed. Through these activities, we developed a 37-item questionnaire that was sent to occupational and physical therapists practicing in Kansas and Missouri who focus on the care of people who have had a stroke (n = 320). A total of 107 respondents returned a com pleted questionnaire, which gives a response rate of about 36%. The majority of respondents had more than 12 years of experience treating patients with stroke. Consensus of 70% or more was found for 80% of the items. The preferred approaches for the rehabilitation of people who have had a stroke are the Bobath and Brunnstrom methods, which are being used by 93% and 85% of the physical and occupational therapists, respectively. Even though some variability existed in certain parts of the survey, in general clinicians agreed on different treatment approaches in issues dealing with muscle tone, weakness, and limited range of motion in stroke rehabilitation. Some newer treatment approaches that have been proven to be effective are practiced only by a minority of clinicians. The uncertainty among clinicians in some sections of the survey reveals that more evidence on clinical approaches is needed to ensure efficacious treatments.

Inadequate dietary n-3 polyunsaturated fatty acid (PUFA) content is associated with altered function of the CNS dopamine systems. In this study, the effects of dietary n-3 PUFA content were determined on dopamine cell number and morphology. Adult (postnatal day 70), male, Long-Evans rats were raised from conception on diets containing adequate (control) or negligible n-3 PUFAs. The number and morphology of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and ventral tegmental area were determined stereologically. The number of tyrosine hydroxylase-positive cells in rats fed the n-3 PUFA-deficient diet was 33.9% lower in the substantia nigra pars compacta and 33.7% lower in the ventral tegmental area than in those fed the control diet (P

Assessment of critical thinking objectives in a pharmacy program curriculum is an important part of program assessment. This study measures the proportion of cognitive learning objectives at various levels of Bloom's taxonomy throughout the required curriculum using the stated objectives in course syllabi (the explicit curriculum). In one entry level doctor of pharmacy program, 54.90% of cognitive objectives identified critical thinking outcomes using the rubric of Bloom's level 3 or higher as an indicator of critical thinking. In this program, there was a similar percent of critical thinking objectives in each of the first three years, but the final year of the curriculum had a higher percent of critical thinking objectives than each of the first three years (p = 0.0018, Kruskal-Wallis test). The increase in critical thinking in the final year suggests that the explicit expectations in the syllabi are weighted toward a higher percent of critical thinking objectives during clinical rotations. The methods described in the study may serve as tools for a curriculum committee or program assessment team to compare critical thinking in the curriculum at different points in time, and may assist in curricular mapping efforts. These methods may complement studies measuring the implicit curriculum (that which the faculty actually teach, which may not be stated in the explicit curriculum.).