BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson’s disease

Real, Caroline Cristiano; Ferreira, Ademar; Chaves-Kirsten, Gabriela P.; Torrão, Andréa da Silva; Pires, Raquel S.; Britto, Luiz Roberto Giorgetti de

doi:10.1016/j.neuroscience.2013.01.060

Cited by 97 publications

(95 citation statements)

References 45 publications

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“…In rodents, wheel running after stimulant exposure produces significant changes in gene transcription factors capable of modulating dopaminergic neurotransmission in the mesolimbic pathways (Greenwood et al, 2011;Zlebnik et al, 2014), and wheel running attenuates MPTPinduced damage to dopaminergic cells in wild-type mice, but not in BDNF (+/ − ) knockdown mice (Gerecke et al, 2012). Similarly, BDNF receptor antagonists blocked the effects of treadmill running against damage to dopaminergic neurons, as indicated by preserved levels of tyrosine hydroxlase activity, in a rat model of Parkinson's disease using striatal injection of 6-hydroxydopamine (Real et al, 2013). Some limitations of this study warrant mention.…”

Section: Discussionmentioning

confidence: 99%

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

Robertson

Ishibashi

Chudzynski

et al. 2015

Neuropsychopharmacol

105

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Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BP ND )) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n = 10) or one that received equal-time health education training (n = 9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [ 18 F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BP ND . At baseline, striatal D2/D3 BP ND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BP ND , whereas those in the education group did not. There were no changes in D2/D3 BP ND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

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Section: Discussionmentioning

confidence: 99%

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

Robertson

Ishibashi

Chudzynski

et al. 2015

Neuropsychopharmacol

105

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“…The concentration of K252a was chosen based on its effective blockade for BDNF receptor TrkB [23, 24]. Prior to injection,, 2–5% isoflurane anesthesia was administered to the rats using a Mobile Laboratory Animal Anesthesia System (VetEquip Inc., CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Flavonoid derivative 7,8-DHF attenuates TBI pathology via TrkB activation

Agrawal

Noble

Tyagi

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Traumatic brain injury (TBI) is followed by a state of metabolic dysfunction, affecting the ability of neurons to use energy and support brain plasticity; there is no effective therapy to counteract the TBI pathology. Brain-derived neurotrophic factor (BDNF) has an exceptional capacity to support metabolism and plasticity, which highly contrasts with its poor pharmacological profile. We evaluated the action of a flavonoid derivative 7,8-dihydroxyflavone (7,8-DHF), a BDNF receptor (TrkB) agonist with the pharmacological profile congruent for potential human therapies. Treatment with 7,8-DHF (5 mg/kg, ip, daily for 7 days) was effective to ameliorate the effects of TBI on plasticity markers (CREB phosphorylation, GAP-43 and syntaxin-3 levels) and memory function in Barnes maze test. Treatment with 7,8-DHF restored the decrease in protein and phenotypic expression of TrkB phosphorylation after TBI. In turn, intrahippocampal injections of K252a, a TrkB antagonist, counteracted the 7,8-DHF induced TrkB signaling activation and memory improvement in TBI, suggesting the pivotal role of TrkB signaling in cognitive performance after brain injury. A potential action of 7,8-DHF on cell energy homeostasis was corroborated by the normalization in levels of PGC-1α, TFAM, COII, AMPK and SIRT1 in animals subjected to TBI. Results suggest a potential mechanism by which 7,8-DHF counteracts TBI pathology via activation of the TrkB receptor and engaging the interplay between cell energy management and synaptic plasticity. Since metabolic dysfunction is an important risk factor for the development of neurological and psychiatric disorders, these results set a precedent for the therapeutic use of 7,8-DHF in a larger context.

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“…The exception tends to be animal models of neurodegenerative disorders that affect other brain regions such as the striatum in PD (Real et al 2013) and Huntington's disease (Pang et al 2006, Potter et al 2010) models. Although we cannot yet measure BDNF receptor density in the human brain noninvasively, one approach for mapping change in growth factors to regional change in structure and function of the human brain from exercise treatment is to examine if acute and chronic exercise-induced change in systemic growth factors is associated with specific change in cognitive performance or brain function measures.…”

Section: Molecular and Cellular Benefits Of -Physical Activity: Evidementioning

confidence: 99%

Physical Activity and Cognitive Vitality

Prakash

Voss

Erickson

et al. 2015

Annu. Rev. Psychol.

277

228

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We examine evidence supporting the associations among physical activity (PA), cognitive vitality, neural functioning, and the moderation of these associations by genetic factors. Prospective epidemiological studies provide evidence for PA to be associated with a modest reduction in relative risk of cognitive decline. An evaluation of the PA-cognition link across the life span provides modest support for the effect of PA on preserving and even enhancing cognitive vitality and the associated neural circuitry in older adults, with the majority of benefits seen for tasks that are supported by the prefrontal cortex and the hippocampus. The literature on children and young adults, however, is in need of well-powered randomized controlled trials. Future directions include a more sophisticated understanding of the dose-response relationship, the integration of genetic and epigenetic approaches, inclusion of multimodal imaging of brain-behavior changes, and finally the design of multimodal interventions that may yield broader improvements in cognitive function.

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BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson’s disease

Cited by 97 publications

References 45 publications

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment

Flavonoid derivative 7,8-DHF attenuates TBI pathology via TrkB activation

Physical Activity and Cognitive Vitality

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