Cristy Phillips

Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling

While the relationship between increased physical activity and cognitive ability has been conjectured for centuries, only recently have the mechanisms underlying this relationship began to emerge. Convergent evidence suggests that physical activity offers an affordable and effective method to improve cognitive function in all ages, particularly the elderly who are most vulnerable to neurodegenerative disorders. In addition to improving cardiac and immune function, physical activity alters trophic factor signaling and, in turn, neuronal function and structure in areas critical for cognition. Sustained exercise plays a role in modulating anti-inflammatory effects and may play a role in preserving cognitive function in aging and neuropathological conditions. Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. Given the growing number of individuals with cognitive impairments worldwide, a better understanding of how these factors contribute to cognition is imperative, and constitutes an important first step toward developing non-pharmacological therapeutic strategies to improve cognition in vulnerable populations.

The role of NMDA receptors in the pathophysiology and treatment of mood disorders.

Mood disorders such as major depressive disorder and bipolar disorder are chronic and recurrent illnesses that cause significant disability and affect approximately 350 million people worldwide. Currently available biogenic amine treatments provide relief for many and yet fail to ameliorate symptoms for others, highlighting the need to diversify the search for new therapeutic strategies. Here we present recent evidence implicating the role of N-methyl-D-aspartate receptor (NMDAR) signaling in the pathophysiology of mood disorders. The possible role of NMDARs in mood disorders has been supported by evidence demonstrating that: (i) both BPD and MDD are characterized by altered levels of central excitatory neurotransmitters; (ii) NMDAR expression, distribution, and function are atypical in patients with mood disorders; (iii) NMDAR modulators show positive therapeutic effects in BPD and MDD patients; and (iv) conventional antidepressants/mood stabilizers can modulate NMDAR function. Taken together, this evidence suggests the NMDAR system holds considerable promise as a therapeutic target for developing next generation drugs that may provide more rapid onset relief of symptoms. Identifying the subcircuits involved in mood and elucidating the role of NMDARs subtypes in specific brain circuits would constitute an important step toward the development of more effective therapies with fewer side effects.

Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimers disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimers disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration.

Mechanisms of action and clinical efficacy of NMDA receptor modulators in mood disorders

Although the biogenic amine models have provided meaningful links between clinical phenomena and pharmacological management of mood disorders (MDs), the onset of action of current treatments is slow and a proportion of individuals fail to adequately respond. A growing number of investigations have focused on the glutamatergic system as a viable target. Herein we review the putative role of N-methyl-d-aspartate (NMDA) signaling in the pathophysiology of MDs. Prompting this focus are several lines of evidence: 1) altered glutamate and NMDA receptor (NMDAR) expression and functioning; 2) antidepressant effects of NMDAR signaling blockers; 3) interaction between conventional therapeutic regimens and NMDAR signaling modulators; 4) biochemical evidence of interaction between monoaminergic system and NMDAR signaling; 5) interaction between neurotrophic factors and NMDAR signaling in mood regulation; 6) cross-talk between NMDAR signaling and inflammatory processes; and 7) antidepressant effects of a number of NMDA modulators in recent clinical trials. Altogether, these studies establish a warrant for the refinement of novel compounds that target glutamatergic mechanisms for the treatment of MDs.

A Special Regenerative Rehabilitation and Genomics Letter: Is There a "Hope" Molecule?

We are delighted to see the dedication of a special series to regenerative rehabilitation and genomics. There is no doubt that an increased focus on genetically driven responses to injury, disease, and aging will enhance prevention and treatment efforts for a number of conditions. Among those well-positioned to benefit from this progress are individuals with mood disorders, which has prompted us to alert our colleagues about recent progress in elucidating the molecular mechanisms that underlie musculoskeletal and central nervous system interdependence, knowledge that may be deployed to prevent and treat stress-related depression in the near future.

Assessment of dendritic arborization in the dentate gyrus of the hippocampal region in mice.

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity and extent of dendritic arborization correlates well with the synaptic plasticity in these cells. A reliable method for assessment of dendritic arborization is needed to characterize the deleterious effects of neurological disorders on these structures and to determine the effects of therapeutic interventions. However, quantification of these structures has proven to be a formidable task given their complex and dynamic nature. Fortunately, sophisticated imaging techniques can be paired with conventional staining methods to assess the state of dendritic arborization, providing a more reliable and expeditious means of assessment. Below is an example of how these imaging techniques were paired with staining methods to characterize the dendritic arborization in wild type mice. These complementary imaging methods can be used to qualitatively and quantitatively assess dendritic arborization that span a rather wide area within the hippocampal region.

Pedunculopontine Gamma Band Activity and Development

This review highlights the most important discovery in the reticular activating system in the last 10 years, the manifestation of gamma band activity in cells of the reticular activating system (RAS), especially in the pedunculopontine nucleus, which is in charge of waking and rapid eye movement (REM) sleep. The identification of different cell groups manifesting P/Q-type Ca2+ channels that control waking vs. those that manifest N-type channels that control REM sleep provides novel avenues for the differential control of waking vs. REM sleep. Recent discoveries on the development of this system can help explain the developmental decrease in REM sleep and the basic rest-activity cycle.

Immune and Neuroprotective Effects of Physical Activity on the Brain in Depression

Physical activity—a lifestyle factor that is associated with immune function, neuroprotection, and energy metabolism—modulates the cellular and molecular processes in the brain that are vital for emotional and cognitive health, collective mechanisms that can go awry in depression. Physical activity optimizes the stress response, neurotransmitter level and function (e.g., serotonergic, noradrenergic, dopaminergic, and glutamatergic), myokine production (e.g., interleukin-6), transcription factor levels and correlates [e.g., peroxisome proliferator-activated receptor C coactivator-1α [PGC-1α], mitochondrial density, nitric oxide pathway activity, Ca2+ signaling, reactive oxygen specie production, and AMP-activated protein kinase [AMPK] activity], kynurenine metabolites, glucose regulation, astrocytic health, and growth factors (e.g., brain-derived neurotrophic factor). Dysregulation of these interrelated processes can effectuate depression, a chronic mental illness that affects millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility in understanding chronic depression, a need remains to better understand the interrelated mechanisms that contribute to immune dysfunction and the means by which various therapeutics mitigate them. Fortunately, convergent evidence suggests that physical activity improves emotional and cognitive function in persons with depression, particularly in those with comorbid inflammation. Accordingly, the aims of this review are to (1) underscore the link between inflammatory correlates and depression, (2) explicate immuno-neuroendocrine foundations, (3) elucidate evidence of neurotransmitter and cytokine crosstalk in depressive pathobiology, (4) determine the immunomodulatory effects of physical activity in depression, (5) examine protocols used to effectuate the positive effects of physical activity in depression, and (6) highlight implications for clinicians and scientists. It is our contention that a deeper understanding of the mechanisms by which inflammation contributes to the pathobiology of depression will translate to novel and more effective treatments, particularly by identifying relevant patient populations that can benefit from immune-based therapies within the context of personalized medicine.

Deploying physical activity for cognitive health in persons at risk for Alzheimer’s disease

Relevance: OA knee is one of the most common conditions leading functional disabilities seen worldwide. There are different methods to manage osteoarthritis, conservatively, and/or surgically. Physiotherapy treatment, as a part of conservative management, involves reduction of pain, improvement of muscle strength and improvement of functional ability by various approaches like exercise therapy, electrotherapy and manual therapy techniques. Quadriceps muscle weakness is one of the main features seen in OA knee. Russian current stimulation has been successfully used to increase muscle strength in healthy athletes but its effect on quadriceps muscle strength in OA knee has not been studied. Hence the present study was undertaken to know the effect of Russian current stimulation on quadriceps muscle strength in patients with primary OA knee. Participants: 30 subjects (mean age 50.25±6.35 years) diagnosed with primary OA knee were recruited from Out-Patient Department of Physiotherapy of KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belgaum. Method: Subjects were randomly allocated into 2 groups namely Group A (n=15) who received Short Wave Diathermy (SWD) and exercises and Group B (n=15) who received SWD, exercises and Russian current stimulation for 10 days. The outcome measures were Visual Analog Scale (VAS) for pain, muscle strength by using Handheld dynamometer, and WOMAC osteoarthritis index for functional disability. Analysis: Within group and between group analysis after intervention was done to assess changes using paired t-test and unpaired t - tests. Result: The VAS scores for group A reduced from 6.8±1.49 (baseline) to1.4±0.91 (post-intervention) and for group B from 6.3±1.29 (baseline) to 1±1.14 (post-intervention). The WOMAC score of group A decreased from 59.7±11.56 (baseline) to 24.1±6.01 (post-intervention) and of group B decreased from 50.4±22.30 (baseline) to 12.5±7.54 (post-intervention). The muscle strength of group A increased from 7.9±0.94 (baseline) to 8.6±0.95 (post-intervention) and of group B it increased from 8.3±0.67 (baseline) to 10.6±0.89 (post-intervention).Group B showed better improvement in muscle strength and function than group A. The intra group and between group comparison was statistically significant with p= <0.001 for both the groups. Conclusion: Russian current stimulation is effective in increasing quadriceps muscle strength and secondarily improving the functional ability in subjects with primary OA knee.Results: Weaning success was present in 76.5% and weaning failure in 17.5% of patients. There were 6% of reintubations. The predictive power for RR weaning failure, RR best cut-off point > 24 breaths per minute (bpm), was: Sensitivity 100%, specificity 85%, and accuracy 88% (ROC curve, p 24 bpm). There were 15% false positives, weaning successes with RR>24 bpm.Introduction: Internet is one of the fastest growing media for Human Resources and Development (HRD). Computer has become an essential part of our Activities of Daily Livings (ADLs) at one hand and other hand, prolonged computer usage has increases the risk of occupational hazards. Prolonged Static work at computer system is a causative factor for poor postural ergonomic, structural derangements and dysfunction commonly at neck, shoulder and low back structures to develop functional limitation and progressively functional disabilities. The basic health education (HE) by means of ergonomic advises and exercise therapy may have efficacy to promote, prevent and cure for such FDs. However, internet itself can be a mode of HE system to be provided at workplace to cut the time & cost together. Purpose of Study: To find the efficacy of IBM for FDs of the computer users. Materials: Internet supported computer, web-site (www.ptmovements.com), web pages, basic health assessment form, Self Reported FD Questioners, Neck Disability Index (NDI) & Back Pain Functional Scale (BPFS), Study Design: Experimental Clinical Trial Methodology: 1256 computer users (M=867) participated online and assess for inclusive & exclusive criterions. Internet based self reported FDs questioners used to assess FDs in prior and post to two weeks of tailor made treatment program. Data Analysis: significance of FDs and impact of IBM on FDs was analyzed with SPSS -17, LOS set at 0.05 or CI 95 % Result: mild to moderate prevalence of FDs was higher neck & shoulder as compared to low back structures. The IBM has shown efficiency to reduce the level of FDs at NDI, and BPFS. Discussion: The internet based health education (IBHE) is well possible to deliver and to reduce the FDs. The advantage of time & cost effective approach in IBM has facilitated keen interest among computer users. Conclusion: The IBHE is well efficient and prospective to develop scopes of “workplace wellness” to promote, prevents, and cures for occupational diseases & disorders. E-health education has great prospectus in field of modern medicine. [ Rathod P et al NJIRM 2011; 2(4) : 77-82]T presentation is to understand comprehensive postural compensation patterns based on kinetic data on the ground as well as kinematic data from trunk motion to assess balance. Firstly, positional-dependent spinal loading with trunk motion is important to relate with center of pressure from the ground for effective rehabilitation intervention and strategies. The combined kinetic and kinematic measurements lead to a better understanding of spinal movement patterns to clarify the relationship between kinematic and kinetic changes in subjects with recurrent LBP. The first part of my presentation is to provide assessment tools for normalized kinematic and kinetic stability indices while considering visual input during one leg standing. Secondly, the shoulder and pelvis kinematics will be compared based on range of motion (ROM), angular velocity, and relative phase (RP) values during trunk axial rotation. The results of this study will be included the difference in should and pelvic girdle motion in the transverse plane during axial trunk rotation. This pattern of trunk movement could be due to possible pelvic stiffness with neuromuscular constraints. Since subjects with recurrent LBP demonstrated decreased pelvic rotation compared to the shoulder for postural control, increased pelvic flexibility could enhance coordinated movement patterns in order to integrate spinal motion.A commonly disrupts the balance control and compensatory postural responses that contribute to maintaining balance and preventing falls during perturbation of posture due to the weakness of lower limb muscles. For prevention of fall, certain fall prevention programs has to be given to the patients which will mainly focus on the stimulation of primary muscle groups of lower limb that will help in activating the normal balance strategies. The purpose of the study was to establish the effect of PBBT (Perturbation Based Balance Training) added to strengthening and balance exercises in improving balance and to reduce falls among older adults. Forty elderly patients aged 65 to 80 years were randomized in two groups by using block randomization. To the group 1 treatment given was standardized OET which is a set of leg muscle strengthening and balance retraining exercises designed specifically to prevent falls. Group 2 was given PBBT along with OET (Otago Exercise Training). Outcome variables measured on force plate are maximum Center of pressure excursion, minimum Center of pressure excursion and stability score. Other then force plate variables the outcome measure taken was TUG (Timed Up & Go Test). The results were checked after two months. Treatment effect was checked within the group by using paired t test and between the groups by using unpaired t test. The results showed significant difference in values of maximum Center of pressure excursion, minimum Center of pressure excursion and stability score in all the four conditions which are NS EO (Normal Stability Eyes Open), NS EC (Normal Stability Eyes Closed), PS EO (Perturbation Stability Eyes Open) & PS EC (Perturbation Stability Eyes closed) within the group. There was also a significant reduction in the values of TUG. Between groups analysis also show significant effect between both the groups. Findings of this study showed better results in the patients belong to group 2 which were given PBBT along with OET. The PBBT is a useful program for fall prevention. It is also inexpensive and compact commercial perturbation-delivery system which would promote widespread clinical application.