Browsing by Subject "aging"

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A Collaborative Implementation Strategy to Increase Falls Prevention Training Using the Age-Friendly Health Systems Approach
(MDPI, 2022-05-12) Severance, Jennifer J.; Rivera, Solymar; Cho, Jinmyoung; Hartos, Jessica; Khan, Amal; Knebl, Janice
Falls in the home and in community environments are the leading cause of injuries and long-term disabilities for the aging population. The purpose of this study was to examine outcomes of a partnership among an academic institution, government agency, community organizations, and emergency management services to implement a falls prevention training program using an Age-Friendly Health Systems approach. In this prospective study, partners identified gaps in services and targeted and non-targeted delivery areas for implementation of an evidence-based falls prevention intervention addressing the 4Ms of Age-Friendly Health Systems-Mobility, Medications, Mentation, and What Matters. Descriptive statistics were calculated for program implementation and participant demographic variables, and paired t-test analysis compared scores for self-assessed general health and falls efficacy prior to and after program participation. Twenty-seven falls prevention classes were implemented, with over half (52%) in targeted areas. A total of 354 adults aged 50 and older participated, with N = 188 participants (53%) completing the program by attending at least five of eight sessions. Of completers, 35% resided in targeted areas. The results showed a statistically significant improvement in falls efficacy by program completers in targeted and non-targeted areas. However, there was no statistically significant difference in self-rated health. Overall, the findings of this study indicate that collaboration to deliver falls prevention training can be effective in reaching at-risk older adults. By mobilizing collaborative partnerships, limited resources can be allocated towards identifying at-risk older adults and improving community-based falls prevention education.
A Microcirculatory Theory of Aging
(JKL International, 2019-06-01) Jin, Kunlin
Aging is the progressive decline of physiological functions necessary for survival and reproduction. In gaining a better understanding of the inevitable aging process, the hope is to preserve, promote, or delay healthy aging through the treatment of common age-associated diseases. Although there are theories that try to explain the aging process, none of them seem to fully satisfy. Microcirculation describes blood flow through the capillaries in the circulatory system. The main functions of the microcirculation are the delivery of oxgen and nutrients and the removal of CO2, metabolic debris, and toxins. The microcirculatory impairment or dysfunction over time will result in the accumulation of toxic products and CO2 and loss of nutrition supplementation and O2 in corresponding tissue systems or internal organs, which eventually affect normal tissue and organ functions, leading to aging. Therefore, I propose a microcirculatory theory of aging: aging is the process of continuous impairment of microcirculation in the body.
Aging Confers an Increase in Sensitivity and Sensitization to Pain and Results in Shifts of Spinal NR1 expression
(2009-05-01) Jenschke, Monica L; Ratka, Anna; Forster, Michael J.
Purpose: Many elderly experience inadequate postoperative pain relief resulting in increased morbidity and mortality. Several experimental models of postoperative pain have been developed but none were adapted to study the effects of aging on the postoperative pain. Review of literature explored current knowledge of postoperative pain models and identified several models suitable for aging studies. A unique model of postoperative pain, the dorsal hairy skin incision model, was modified and adopted for aged rats. Using this model, we tested two hypotheses: a) aged rats will exhibit similar intensity but longer duration of postincision hyperalgesia compared to young rats and b) spinal cord NR1 expression will increase in response to nociceptive stimulation and that age-related differences in magnitude of NR1 expression will be evident. Methods: In study I, young (5-7 months old) and aged (22-23 months old) male Fischer 344 rats were exposed to nociceptive testing with von Frey filaments and the cutaneous trunci muscle reflex was measured. For each stimulation, a graded response of 0, 0.5, or 1, for no reflex, a small reflex, or vigorous reflex, respectively was recorded. After baseline testing, a 2 cm incision was made through the dorsal skin followed by skin closure and recovery. Subsequently, rats were tested at 3 hours, 6 hours, and on postoperative days (POD) 1, 3, 6, 10, and 14. In study II, young (4-6 months old) and aged (19-21 months old) male Fischer 344 rats were subjected to three sessions of mechanical nociceptive stimulus. After testing, spinal cords were harvested for western blot analysis of NR1 expression. Results: In study I, aged rats had greater baseline graded responses to nociceptive stimuli. After incision, young rats developed primary allodynia lasting until POD 3 and primary hyperalgesia until POD 8. Aged rats did not develop allodynia or primary hyperalgesia. Neither group developed secondary hyperalgesia. Aged rats demonstrated greater sensitivity to baseline nociceptive testing and greater maximal graded responses to repetitive testing sessions. In young rats, nociceptive stimulation resulted in a significant increase in NR1 expression. Increased NR1 expression in young tested rats positively correlated with an increase in graded response for one of 18 session/region/force categories tested. There was no increase in spinal cord NR1 expression in aged rats in response to nociceptive stimulation. Low NR1 expression in aged tested rats negatively correlated with an increase in graded response for 9 of 18 session/region/force categories tested. Conclusions: An experimental rat model to study effects of age on postoperative pain is presented. Age has a profound impact on the pre- and postoperative periods. Aged rats differ significantly from young rats in sensitivity and maximal graded response to acute incisional pain. Young rats exposed to mechanical punctate nociceptive stimuli experienced increased NR1 expression which positively correlated with an increase in graded response. In contrast, aged rats with decreased NR1 expression negatively correlated with an increased graded response. Lower sensitivity and maximal graded responses in the young rats reflect an intact endogenous modulatory pain pathway. Greater sensitivity and maximal graded responses in the aged rats reflect impairment of descending modulatory pain pathways.
Aging During the Pandemic: Untangling the Complexities of COVID-19 and Geriatric Care
(JKL International, 2023-05-16) Su, Kaimeng; Jin, Kunlin
The COVID-19 pandemic has posed unprecedented challenges to the global healthcare system, with the elderly population being particularly vulnerable. This comprehensive review synthesizes the findings from publications in "Aging and Disease", highlighting the unique challenges older adults encountered during the pandemic and providing solutions thereof. These studies provide invaluable insights into the elderly population's vulnerabilities and needs during the COVID-19 pandemic. The susceptibility to the virus in older individuals remains debatable, and research on the clinical picture of COVID-19 in older populations has yielded insights into clinical features, molecular mechanisms, and potential therapeutic strategies. This review intends to shed light on the need of sustaining physical and mental well-being among older adults during the periods of lockdown by extensively exploring these concerns and emphasizing the need for targeted interventions and support systems for this population. Ultimately, the findings of these studies contribute to developing more effective and comprehensive approaches to managing and mitigating the risks posed by the pandemic to the elderly.
Aging impairs regulatory T cells to affect the mouse model of late-onset multiple sclerosis
(2022-08) Wang, Weikan; Su, Dong-Ming; Berg, Rance E.; Bunnell, Bruce A.; Yang, Shaohua; Jones, Harlan P.; Zode, Gulab S.
Although multiple sclerosis (MS) primarily onsets in young adults, it can also develop in the elderly, which is termed late-onset (aged) MS. CD4+ Foxp3 + regulatory T (Treg) cells play an ameliorative role in severity of MS or its animal model experimental autoimmune encephalomyelitis (EAE), and the aged immune system accumulates peripheral Treg (pTreg) cells. However, late-onset MS in the aged patients presents a more progressive disease course. We investigated why the accumulated pTreg cells fail to ameliorate the MS severity in the aged individuals by using an aged EAE mouse model to recapitulate late-onset MS in patients. We observed that the onset of EAE is delayed in aged mice, but disease severity is increased compared to young EAE mice. We found that the distribution of Treg cells in aged EAE mice exhibited an increased proportion of polyclonal (pan-) pTreg cells and a decreased proportion of antigen specific-pTreg cells in the periphery, but decreased proportions of both pan- and antigen specificTreg cells in the central nervous system (CNS). Transiently inhibiting Foxp3 or depleting pTreg cells partially corrected Treg distribution and restored the balance of effector T cells (Teff) and Treg cells in the aged inflamed CNS, thereby ameliorating the disease in the aged EAE mice. Furthermore, in the aged inflamed CNS, CNS-Treg cells exhibited a high plasticity and T effector (CNS-Teff) cells presented a great clonal expansion, disrupting the Treg/Teff balance. These results provide evidence and mechanism that accumulated aged pTreg cells play a detrimental role in neuronal inflammation of aged MS.
AMP-Activated Protein Kinase (AMPK) signaling regulates the age-related decline of hippocampal neurogenesis
(2018-05) Wang, Brian S.; Jin, Kunlin; Hodge, Lisa M.; Singh, Meharvan; Sumien, Nathalie; Yang, Shaohua
Aging is the progressive decline of physiological function and increased vulnerability to disease and death. By the year 2050, 2 billion people will be over the age of 60. Accompanying this, the incidence of age-associated neurological diseases is expected to rise. Thus, there is an urgent need to find therapies to promote healthy brain aging. The finding that neurogenesis continues into adulthood allows us to target endogenous neurogenesis as a potential therapeutic. However, the number of stem cells can decrease by about 80% in the aged brain and is a main cause for the decrease in brain function. The reasons for the age-related decline in neurogenesis can be due to intrinsic factors such as cell metabolism, which have been studied but its role in neurogenesis remains largely unexplored. Interestingly, neural stem cells (NSCs) possess metabolically different characteristics from their differentiated progeny, suggesting the need for a shift in cellular metabolism to accommodate the requirements for neurogenesis. In the process of the metabolic shift, the AMP-activated protein kinase (AMPK) plays a pivotal role for controlling stem cell proliferation and differentiation as a cell's master metabolic regulator. Additionally, AMPK has been reported to control the functions of signaling pathways that regulate the aging process, which suggests its potential involvement in the age-related decline of neurogenesis. Therefore, we hypothesize that inhibition of AMPK signaling activation (phosphorylation) in the old brain will cause a concomitant increase in hippocampal neurogenesis. Our specific aim is to establish whether AMPK signaling plays a critical role in the age-related decline of hippocampal neurogenesis. Our objectives for this aim are to (i) determine the expression pattern of AMPK in the subgranular and subventricular zones of young-adult and old mice using immunohistochemistry and Western blotting; and (ii) examine the impact of loss or gain of AMPK activation on hippocampal neurogenesis in young-adult and old mice using pharmacological agents Compound C (AMPK inhibitor) and 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR, AMPK activator). Our results show that (i) AMPK subunit isoforms are differentially expressed in the neurogenic regions – most are localized to the cytoplasm in the subgranular zone (SGZ) with the exception of α2 and β1, while most isoforms are found in the nucleus in the subventricular zone (SVZ) except α1; (ii) AMPK signaling activation was significantly increased in the SGZ and SVZ; and (iii) short-term but not long-term pharmacological inhibition of AMPK signaling could partially rescue hippocampal neurogenesis in the old brain. Taken together, these results indicate that AMPK is a critical mediator in the regulation of downstream processes for the age-related decline in hippocampal neurogenesis.
AMPK Signaling Regulates the Age-Related Decline of Hippocampal Neurogenesis
(JKL International, 2019-10-01) Wang, Brian Z.; Yang, Jane J.; Zhang, Hongxia; Smith, Charity A.; Jin, Kunlin
The global incidence of age-associated neurological diseases is expected to rise with increasingly greying societies. In the aged brain, there is a dramatic decrease in the number of stem cells, which is a main cause for the decrease in brain function. Intrinsic factors, such as cell metabolism, have been studied but its role in neurogenesis is still unknown. Therefore, this study sought to establish whether AMP-activated protein kinase (AMPK) signaling does indeed regulate hippocampal neurogenesis in the aged brain. We found that i) AMPKalpha2 was the predominant catalytic subunit in the subgranular and subventricular zones; ii) AMPK activation was at a significantly higher level in the aged vs. young hippocampus; iii) short term (7 days) treatment with selective AMPK signaling inhibitor Compound C (10 mg/kg/day, i.p.) significantly increased the numbers of newborn (BrdU(+)), Type 2 (MCM2(+)), and Type 3 (DCX(+)) neural stem cells, but not Type 1 (GFAP(+)/Sox2(+)) cells, in the aged hippocampus. Taken together, our results demonstrate that AMPK signaling plays a critical role in the age-related decline of hippocampal neurogenesis.
Antioxidants, Exercise, and Brain Function
(2015-12-01) Sidhu, Akram; Sumien, Nathalie; Forster, Michael J.; Gonzales, Eric B.
Aging is associated with a decline in psychomotor and cognitive function. Interventions such as exercise and antioxidants supplementation when investigated independently have been beneficial counteracting oxidative stress and improving brain function in both human and animals. A large number of health conscious individuals often combine exercise with vitamin supplementation, anticipating a synergistic effect maximizing their performance. While some studies reported additive effects, others have also indicated a potential for an antagonistic action of the antioxidants on the beneficial effects of exercise. To date, it has not been well established what the nature of the interaction between antioxidant supplementation and exercise is in terms of functional outcomes and whether age will influence the outcomes. The purpose of this study was to determine if combination of antioxidant supplementation, and moderate exercise could ameliorate psychomotor and cognitive performance of young and old male mice Using vitamins C and E and a treadmill-based forced exercise in young and old C57BL/6J mice, we explored the nature of that interaction on functional and biochemical outcomes. We examined the mice for spatial learning and memory, working memory and executive function, coordinated running performance, muscular reflexes, spontaneous locomotor activity, anxiety and muscle strength. Our data suggested that the male mice exhibited age-associated declines in psychomotor and cognitive performance. Antioxidants supplementation worsened the cognitive flexibility of old mice but improved the depression-like symptoms in young mice. Overall, exercise training reversed the age-related declines in reflexes and balance of old mice, and improved strength and associative learning of young mice only. Furthermore, combination of exercise and antioxidant improved reflexes, motor and cognitive performance, but additive or antagonistic effects of antioxidants on the beneficial effects of exercise were not observed. Hence we can conclude that, combining antioxidants and exercise may not be provide any additional benefit in reversing age-related functional impairments.
ApoE Genotype-Dependent Response to Antioxidant and Exercise Interventions on Brain Function
(MDPI, 2020-06-25) Chaudhari, Kiran; Wong, Jessica M.; Vann, Philip H.; Como, Tori; O'Bryant, Sid E.; Sumien, Nathalie
This study determined whether antioxidant supplementation is a viable complement to exercise regimens in improving cognitive and motor performance in a mouse model of Alzheimer's disease risk. Starting at 12 months of age, separate groups of male and female mice expressing human Apolipoprotein E3 (GFAP-ApoE3) or E4 (GFAP-ApoE4) were fed either a control diet or a diet supplemented with vitamins E and C. The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure reflex and motor, cognitive, and affective function while remaining on their treatment. Subsequently, plasma inflammatory markers and catalase activity in brain regions were measured. Overall, the GFAP-ApoE4 mice exhibited poorer motor function and spatial learning and memory. The treatments improved balance, learning, and cognitive flexibility in the GFAP-ApoE3 mice and overall the GFAP-ApoE4 mice were not responsive. The addition of antioxidants to supplement a training regimen only provided further benefits to the active avoidance task, and there was no antagonistic interaction between the two interventions. These outcomes are indicative that there is a window of opportunity for treatment and that genotype plays an important role in response to interventions.
Blood Inflammatory Exosomes with Age Prime Microglia through Complement Signaling for Negative Stroke Outcomes
(2020-05) Zhang, Hongxia; Jin, Kunlin; Forster, Michael J.; Yang, Shaohua; Shi, Xiangrong; Cunningham, J. Thomas
The systemic inflammatory milieu plays an important role in the age-related decline of functional integrity, but its contribution to age-related disease (e.g., stroke) remains largely unknown. Here, we found that activated complement molecules (C1q, C3a, C3b) in serum exosomes increased with age, whereas CD46, a C3b/C4b-inactivating factor, was higher in serum exosomes from young rats. These serum inflammatory exosomes passed the blood-brain barrier and primed the microglial response that led to exacerbation of synaptic loss and motor deficits after ischemic stroke via microglial C3a receptor (C3aR). When aged rats were exposed to serum exosomes from young rats, microglia-mediated synaptic loss was reduced and motor deficits after stroke were improved. Administration of C3aR inhibitor or microglial depletion attenuated synaptic loss associated with the treatment of serum exosome from aged rats, in parallel with improved post-stroke outcome. Our data suggest that peripheral circulating old exosomes act as inflammatory mediators and influence ischemic stroke outcome through a complement-microglia axis.
Cardiovascular Metrics Associated With Prevention of Aging-Related Parkinsonian Signs Following Exercise Intervention in Sedentary Older Rats
(Frontiers Media S.A., 2021-12-15) Kasanga, Ella A.; Little, Joel; McInnis, Tamara R.; Bugnariu, Nicoleta; Cunningham, J. Thomas; Salvatore, Michael F.
Preservation of motor capabilities is vital to maintaining independent daily living throughout a person's lifespan and may mitigate aging-related parkinsonism, a progressive and prevalent motor impairment. Physically active lifestyles can mitigate aging-related motor impairment. However, the metrics of physical activity necessary for mitigating parkinsonian signs are not established. Consistent moderate intensity (~10 m/min) treadmill exercise can reverse aging-related parkinsonian signs by 20 weeks in a 2-week on, 2-week off, regimen in previously sedentary advanced middle-aged rats. In this study, we initiated treadmill exercise in sedentary 18-month-old male rats to address two questions: (1) if a rest period not longer than 1-week off exercise, with 15 exercise sessions per month, could attenuate parkinsonian signs within 2 months after exercise initiation, and the associated impact on heart rate (HR) and mean arterial pressure (MAP) and (2) if continuation of this regimen, up to 20 weeks, will be associated with continual prevention of parkinsonian signs. The intensity and frequency of treadmill exercise attenuated aging-related parkinsonian signs by 8 weeks and were maintained till 23 months old. The exercise regimen increased HR by 25% above baseline and gradually reduced pre-intervention MAP. Together, these studies indicate that a practicable frequency and intensity of exercise reduces parkinsonian sign severity commensurate with a modest increase in HR after exercise. These cardiovascular changes provide a baseline of metrics, easily measured in humans, for predictive validity that practicable exercise intensity and schedule can be initiated in previously sedentary older adults to delay the onset of aging-related parkinsonian signs.
Cell-Free mtDNA Quantification in Alzheimer's Patients from the Mexican American Population
(2020-05) House, Sara R.; Phillips, Nicole R.; Hodge, Lisa M.; Zascavage, Roxanne R.
Abstract Background AD is a continuous problem in the 65+ population but it is especially challenging in the Hispanic population where not only is it more prevalent but more severe than Caucasian populations. This study explores the efficacy of using peripheral blood plasma as an alternative tissue for testing as well as the usefulness for future research assisting in identifying the population structure most at risk for developing AD based upon CF-mtDNA quantity results. Materials and Methods Samples tested included a total cohort (Mexican American and Caucasian) of 177 individuals (AD=45, MCI=74, NC=58). The Mexican American subset contained 92 individuals (AD=21, MCI=53, and NC=18). Peripheral blood plasma was collected from the TARCC biobank and quantified. CF-mtDNA was then tested for significance using correlation analyses, logistic and linear regression models. Results CF-mtDNA was significantly negatively correlated with education, age, sex, and hypertensive samples in the total and Mexican American populations. The greatest difference was expected to be in CF-mtDNA quantity from NC to AD samples. Instead, the most significant difference was between MCI and NC samples. As CF-mtDNA quantity increased, the MMSE and CDRSOB scores were less impaired. Conclusion In conclusion, CF-mtDNA is an easily accessible and easily tested molecular marker of diseases that are relevant to studies for cognitive decline. Although our findings were inconsistent with current literature, they bring to light the weight of confounding factors within limited sample studies. With the completion of the full sample set associated with this study, more power is needed to overcome these issues.
Chronic testosterone deprivation sensitizes the middle-aged rat brain to damaging effects of testosterone
(2020-05) Smith, Charity; Schreihofer, Derek A.; Cunningham, Rebecca L.; Singh, Meharvan; Yang, Shaohua; Jones, Harlan P.
Levels of the testosterone (T) fall in aging men. Recently, the number of men obtaining testosterone replacement therapy (TRT) has increased dramatically. However, other consequences of aging, such as increased oxidative stress, may result in detrimental effects when combined with TRT, including an increased stroke risk. Whether such a delay would alter the effects of TRT on stroke is not known. We hypothesized that a delay TRT following castration in middle-aged male rats would result in increased oxidative stress and a reduction in the neuroprotective effects of testosterone following stroke. We evaluated the effects of testosterone treatment after short (2 week) and long-term testosterone deprivation (10 weeks) in middle-aged male rats on cerebral ischemia, oxidative stress and cognitive function. Our data suggest testosterone treatment after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia, however in the absence of injury improves cognition. Both effects are regulated by oxidative stress.
Combining Injectable Plasma Scaffold with Mesenchymal Stem/Stromal Cells for Repairing Infarct Cavity after Ischemic Stroke
(JKL International, 2017-04-01) Zhang, Hongxia; Sun, Fen; Wang, Jixian; Xie, Luokun; Yang, Chenqi; Pan, Mengxiong; Shao, Bei; Yang, Guo-Yuan; Yang, Shaohua; Zhuge, Qichuan; Jin, Kunlin
Stroke survivors are typically left with structural brain damage and associated functional impairment in the chronic phase of injury, for which few therapeutic options exist. We reported previously that transplantation of human embryonic stem cell (hESC)-derived neural stem cells together with Matrigel scaffolding into the brains of rats after focal ischemia reduced infarct volume and improved neurobehavioral performance. Matrigel is a gelatinous protein mixture extracted from mouse sarcoma cells, thus would not be approved for use as a scaffold clinically. In this study, we generated a gel-like scaffold from plasma that was controlled by changing the concentration of CaCl2. In vitro study confirmed that 10-20 mM CaCl2 and 10-40% plasma did not affect the viability and proliferation of human and rat bone marrow mesenchymal stem/stromal cells (BMSCs) and neural stem cells (NSCs). We transplanted plasma scaffold in combination of BMSCs into the cystic cavity after focal cerebral ischemia, and found that the atrophy volume was dramatically reduced and motor function was significantly improved in the group transplanted with scaffold/BMSCs compared with the groups treated with vehicle, scaffold or BMSCs only. Our data suggest that plasma-derived scaffold in combination of BMSCs is feasible for tissue engineering approach for the stroke treatment.
Current Strategies for Brain Drug Delivery
(Ivyspring International Publisher, 2018-02-05) Dong, Xiaowei
The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.
Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality
(MDPI, 2024-01-23) Salvatore, Michael F.
The mechanistic influences of dopamine (DA) signaling and impact on motor function are nearly always interpreted from changes in nigrostriatal neuron terminals in striatum. This is a standard practice in studies of human Parkinson's disease (PD) and aging and related animal models of PD and aging-related parkinsonism. However, despite dozens of studies indicating an ambiguous relationship between changes in striatal DA signaling and motor phenotype, this perseverating focus on striatum continues. Although DA release in substantia nigra (SN) was first reported almost 50 years ago, assessment of nigral DA signaling changes in relation to motor function is rarely considered. Whereas DA signaling has been well-characterized in striatum at all five steps of neurotransmission (biosynthesis and turnover, storage, release, reuptake, and post-synaptic binding) in the nigrostriatal pathway, the depth of such interrogations in the SN, outside of cell counts, is sparse. However, there is sufficient evidence that these steps in DA neurotransmission in the SN are operational and regulated autonomously from striatum and are present in human PD and aging and related animal models. To complete our understanding of how nigrostriatal DA signaling affects motor function, it is past time to include interrogation of nigral DA signaling. This brief review highlights evidence that changes in nigral DA signaling at each step in DA neurotransmission are autonomous from those in striatum and changes in the SN alone can influence locomotor function. Accordingly, for full characterization of how nigrostriatal DA signaling affects locomotor activity, interrogation of DA signaling in SN is essential.
Editorial: The NLRP3 inflammasome-mediated neuroinflammation and its related mitochondrial impairment in neurodegeneration
(Frontiers Media S.A., 2023-01-31) Deng, Chao; Cai, Xiang; Wang, Qing; Jin, Kunlin
Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats
(IOS Press, 2022-06-28) Salvatore, Michael F.; Soto, Isabel; Kasanga, Ella A.; James, Rachael; Shifflet, Marla K.; Doshier, Kirby; Little, Joel T.; John, Joshia; Alphonso, Helene M.; Cunningham, J. Thomas; Nejtek, Vicki A.
BACKGROUND: Rodent Parkinson's disease (PD) models are valuable to interrogate neurobiological mechanisms of exercise that mitigate motor impairment. Translating these mechanisms to human PD must account for physical capabilities of the patient. OBJECTIVE: To establish cardiovascular parameters as a common metric for cross-species translation of aerobic exercise impact. METHOD: We evaluated aerobic exercise impact on heart rate (HR) in 21 early-stage PD subjects (Hoehn Yahr /=3 months, >/=3x/week. In 4-month-old Pink1 knockout (KO) rats exercising in a progressively-increased treadmill speed regimen, we determined a specific treadmill speed that increased HR to an extent similar in human subjects. RESULTS: After completing aerobic exercise for approximately 30 min, PD subjects had increased HR approximately 35% above baseline ( approximately 63% maximum HR). Motor and cognitive test results indicated the exercising subjects completed the timed up and go (TUG) and trail-making test (TMT-A) in significantly less time versus exercise-naive PD subjects. In KO and age-matched wild-type (WT) rats, treadmill speeds of 8-10 m/min increased HR up to 25% above baseline ( approximately 67% maximum HR), with no further increases up to 16 m/min. Exercised KO, but not WT, rats showed increased locomotor activity compared to an age-matched exercise-naive cohort at 5 months old. CONCLUSION: These proof-of-concept results indicate HR is a cross-species translation parameter to evaluate aerobic exercise impact on specific motor or cognitive functions in human subjects and rat PD models. Moreover, a moderate intensity exercise regimen is within the physical abilities of early-stage PD patients and is therefore applicable for interrogating neurobiological mechanisms in rat PD models.
Gait Analyses in Mice: Effects of Age and Glutathione Deficiency
(International Society on Aging and Disease, 2018-08-01) Mock, J. Thomas; Knight, Sherilynn G.; Vann, Philip H.; Wong, Jessica M.; Davis, Delaney L.; Forster, Michael J.; Sumien, Nathalie
Minor changes (~0.1 m/s) in human gait speed are predictive of various measures of decline and can be used to identify at-risk individuals prior to further decline. These associations are possible due to an abundance of human clinical research. However, age-related gait changes are not well defined in rodents, even though rodents are used as the primary pre-clinical model for many disease states as well as aging research. Our study investigated the usefulness of a novel automated system, the CatWalk XT, to measure age-related differences in gait. Furthermore, age-related functional declines have been associated with decreases in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular shift. Therefore the secondary aim of this study was to determine whether chronic glutathione deficiency led to exacerbated age-associated impairments. Groups of male and female wild-type (gclm(+/+)) and knock-out (gclm(-/-)) mice aged 4, 10 and 17 months were tested on the CatWalk and gait measurements recorded. Similar age-related declines in all measures of gait were observed in both males and females, and chronic glutathione depletion was associated with some delays in age-related declines, which were further exacerbated. In conclusion, the CatWalk is a useful tool to assess gait changes with age, and further studies will be required to identify the potential compensating mechanisms underlying the effects observed with the chronic glutathione depletion.
Gracy, Robert, PhD.
(1994-01-26) Gracy, Robert; Hailey, Blake
Dr. Gracy, Associate Dean of Basic Sciences and Research, recounts the process of bringing TCOM and North Texas together. Interviewed by Blake Hailey, January 26, 1994