Animal studies have been instrumental in providing evidence for exercise-induced neuroplasticity of corticostriatal circuits that are profoundly affected in Parkinson’s disease. Exercise has been implicated in modulating dopamine and glutamate neurotransmission, altering synaptogenesis, and increasing cerebral blood flow. In addition, recent evidence supports that the type of exercise may have regional effects on brain circuitry, with skilled exercise differentially affecting frontal-striatal related circuits to a greater degree than pure aerobic exercise. Neuroplasticity in models of dopamine depletion will be reviewed with a focus on the influence of exercise on the dorsal lateral striatum and prefrontal related circuitry underlying motor and cognitive impairment in PD. Although clearly more research is needed to address major gaps in our knowledge, we hypothesize that the potential effects of exercise on inducing neuroplasticity in a circuit specific manner may occur through synergistic mechanisms that include the coupling of an increasing neuronal metabolic demand and increased blood flow. Elucidation of these mechanisms may provide important new targets for facilitating brain repair and modifying the course of disease in PD.
BackgroundCraniopharyngiomas (CP) are locally invasive and frequently recurring neoplasms often resulting in neurological and endocrinological dysfunction in children. In addition, social-behavioral impairment is commonly reported following treatment for childhood CP, yet remains to be fully understood. The authors aimed to further characterize the prevalence of neurobehavioral, social, and emotional dysfunction in survivors of childhood craniopharyngiomas.Materials and MethodsA systematic literature review was conducted in PubMed to identify studies formally assessing neurobehavioral, social, and emotional outcomes in patients treated for CP prior to 18 years of age. Studies published between the years 1990-2012 that reported the primary outcome (prevalence of neurobehavioral, social, emotional/affective dysfunction, and/or impaired quality of life (QoL)) in ≥10 patients were included.ResultsOf the 471 studies screened, 11 met inclusion criteria. Overall neurobehavioral dysfunction was reported in 51 of 90 patients (57%) with available data. Social impairment (i.e. withdrawal, internalizing behavior) was reported in 91 of 222 cases (41%). School dysfunction was reported in 48 of 136 patients (35%). Emotional/affective dysfunction was reported in 58 of 146 patients (40%), primarily consisting of depressive symptoms. Health related quality of life was affected in 49 of 95 patients (52%). Common descriptors of behavior in affected children included irritability, impulsivity, aggressiveness, and emotional outbursts.ConclusionsNeurobehavioral, social, and emotional impairment is highly prevalent in survivors of childhood craniopharyngioma, and often affects quality of life. Thorough neurobehavioral/emotional screening and appropriate counseling is recommended in this population. Additional research is warranted to identify risk factors and treatment strategies for these disorders.
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid-type glutamate receptor (AMPAR) plays a critical role in modulating experience-dependent neuroplasticity, and alterations in AMPAR expression may underlie synaptic dysfunction and disease pathophysiology. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of dopamine (DA) depletion, our previous work showed exercise increases total GluA2 subunit expression and the contribution of GluA2-containing channels in MPTP mice. The purpose of this study was to determine whether exercise-dependent changes in AMPAR expression after MPTP are specific to the striatopallidal (D2 R) or striatonigral (D1 R) medium spiny neuron (MSN) striatal projection pathways. Drd2 -eGFP-BAC transgenic mice were used to delineate differences in AMPAR expression between striatal D2 R-MSNs and D1 R-MSNs. Striatal AMPAR expression was assessed by immunohistochemical (IHC) staining, Western immunoblotting (WB) of preparations enriched for postsynaptic density (PSD), and alterations in the current-voltage relationship of MSNs. We found DA depletion results in the emergence of GluA2-lacking AMPARs selectively in striatopallidal D2 R-MSNs and that exercise reverses this effect in MPTP mice. Exercise-induced changes in AMPAR channels observed after DA depletion were associated with alterations in GluA1 and GluA2 subunit expression in postsynaptic protein, D2 R-MSN cell surface expression, and restoration of corticostriatal plasticity. Mechanisms regulating experience-dependent changes in AMPAR expression may provide innovative therapeutic targets to increase the efficacy of treatments for basal ganglia disorders, including Parkinson's disease.
Introduction Evidence of a concentration of cigarette advertising in predominantly low-income, non-White neighborhoods underscores the need to examine retail marketing and promotions for novel tobacco products like little cigars and cigarillos (LCCs). We sought to investigate neighborhood racial/ethnic disparities in LCC marketing at retail, including availability, advertising, price promotions, and product placement in Los Angeles, California. Methods Between January 2016 and April 2017, community health workers (n = 19) conducted in-person observational audits from tobacco retail stores (n = 679) located in zip codes with a high percentage of non-Hispanic White (n = 196), Black (n = 194), Hispanic/Latino (n = 189), or Korean American (n = 100) residents. To account for clustering effect of zip codes, multilevel modeling approach for a dichotomized outcome was conducted to evaluate the association between racial/ethnic neighborhood sample and dependent variables. Results Stores located in zip codes with a high percentage of non-Hispanic Blacks had more than eight times higher odds of selling LCCs (OR = 8.10; 95% CI = 3.10–21.11 vs. non-Hispanic White), more than five times higher odds of selling flavored LCCs (OR = 5.20; 95% CI = 2.33–11.61 vs. non-Hispanic White), and more than six times higher odds of displaying storefront exterior LCC signage (OR = 6.03; 95% CI = 2.93–12.40 vs. non-Hispanic White). Stores in Hispanic/Latino and Korean American communities had about three times higher odds of selling LCCs (OR = 3.02; 95% CI = 1.15–7.93 vs. non-Hispanic White; OR = 2.99; 95% CI = 1.33–6.71 vs. non-Hispanic White). Conclusions LCCs are heavily marketed in retail establishments in Los Angeles, with disproportionate targeting of predominantly non-White neighborhoods, especially stores in neighborhoods with a higher proportion of African Americans. Local, state, and federal flavor restrictions, minimum pack size standards, preventive messages, and campaigns could counter the influence of LCC marketing in retail establishments.
Background-Previous youth tobacco research has identified multiple correlated risk factors for initiation of cigarette and e-cigarette use; whether these factors are independently associated with initiation is not known, due to challenges with disentangling the independent effects of these correlated risk factors.Methods-Students in 11 th /12 th grade enrolled in the Southern California Children's Health Study were surveyed in 2014 (baseline) and again in 2015 (N=1553). Structural equation models (SEM) were developed to investigate associations of susceptibility, marketing, and the social environment (as latent factors), and other tobacco use at baseline with cigarette or e-cigarette initiation between baseline and follow-up. Analyses were restricted to baseline never cigarette users (N=1293) for models evaluating cigarette initiation, and to never e-cigarette users (N=1197) for models evaluating e-cigarette initiation.Results-In fully-adjusted prospective SEM models, latent factors for cigarette susceptibility, marketing, and the social environment, along with ever e-cigarette use and ever hookah use at baseline were independently associated with cigarette initiation between baseline and follow-up (P<0.
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