Effect of short-term exercise training on brain-derived neurotrophic factor signaling in spontaneously hypertensive rats

Monnier, Alice; Garnier, Philippe; Quirié, Aurore; Pernet, Nicolas; Demougeot, Céline; Marie, Christine; Prigent‐Tessier, Anne

doi:10.1097/hjh.0000000000001164

Cited by 20 publications

(15 citation statements)

References 56 publications

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“…In agreement with this, BDNF +/− rats exhibited anhedonia and anxiety-like behaviour (15) and the Val66Met polymorphism that results in abnormal BDNF signalling (16) increased the risk of mental diseases (17,18). It is noteworthy that brain BDNF levels are decreased in diseases associated with ED (19,20) or after immune challenge (21).…”

Section: Introductionsupporting

confidence: 53%

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

Totoson¹,

Quirié²,

Pedard³

et al. 2020

Preprint

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Background: To determine vascular and cerebral effects of Tofacitinib in the adjuvant-induced arthritis (AIA) model in rat.Methods: At the first signs of arthritis (day 10-12 post-immunization), Tofacitinib (10 mg/kg s.c., twice daily) or vehicle were administered for 3 weeks in AIA rats. A group of non AIA served as controls. Body weights and arthritis scores were daily monitored. Anhedonia was explored with the saccharin preference test at day 4 (preclinical), day 11 (early) and day 28 (acute arthritis) post-immunization. At the end of the treatment, aorta, brain and blood were collected for analysis of endothelial function using acetylcholine (Ach)-induced relaxation, brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus (Hip) and prefrontal cortex (PFC), and IL-1β, TNFα, IL-17A plasma levels. Radiographic score of paws was also assessed. Results: As compared to vehicle, Tofacitinib reduced body weight loss, arthritis and radiographic scores (p<0.001) but did not change plasma levels of pro-inflammatory cytokines. Tofacitinib fully prevented AIA-associated reduction in Ach-induced relaxation. As compared to controls, vehicle-treated AIA exhibited low BDNF levels in PFC (p<0.001) and anhedonia at all times examined (p<0.05). Tofacinib did not improve anhedonia, but resulted in elevation of BDNF levels both in PFC (p<0.05) and Hip (p<0.001). A positive correlation was observed between brain BDNF levels and endothelial function (p<0.05).Conclusion: Restoration of normal endothelial function and elevation of brain BDNF levels by Tofacitinib in AIA rats support a positive effect of this new antirheumatic drug on cardiovascular and neuropsychiatric comorbidities of rheumatoid arthritis.

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Section: Introductionsupporting

confidence: 53%

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

Totoson¹,

Quirié²,

Pedard³

et al. 2020

Preprint

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“…However, learning is impaired in animal model of RA in which only one hind paw is damaged (Zhu et al, 2016 ). It is noteworthy that diseases other than RA but combining as RA impaired cognition and high cardiovascular risk such as hypertension and diabetes were reported to induce BDNF downregulation in neurons (Pietranera et al, 2010 ; Franco-Robles et al, 2014 ), endothelial cells (Navaratna et al, 2011 ; Prigent-Tessier et al, 2013 ) or both (Monnier et al, 2017a ). Using cell culture, activation of endothelial TrkB receptors was reported to induce myotubes formation (angiogenesis) (Kim et al, 2004 ), while activation of neuronal receptors was reported to increase the number of synaptic connections (Park and Poo, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…We are aware that endothelial BDNF expression in arterioles and cerebral capillaries might differ. However, the difference if present is expected to be minor since endothelial BDNF staining/levels did not singificantly differ amoung F20, F53, and F110 fractions (Monnier et al, 2017a ). According to such a paracrine action, BDNF secreted by cerebral capillaries into the cerebral interstitial fluid might be recognized by and activate neuronal TrkB receptors thereby increasing synapses strength and cognitive abilities.…”

Section: Discussionmentioning

confidence: 99%

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The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or Endothelial, Is Impaired in Rats with Adjuvant-Induced Arthritis. Connection with Endothelial Dysfunction

et al. 2018

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Cognitive abilities are largely dependent on activation of cerebral tropomyosin-related kinase B receptors (TrkB) by brain-derived neurotrophic factor (BDNF) that is secreted under a bioactive form by both neurons and endothelial cells. In addition, there is mounting evidence for a link between endothelial function and cognition even though the underlying mechanisms are not well known. Therefore, we investigated the cerebral BDNF pathway, either neuronal or endothelial, in rheumatoid arthritis (RA) that combines both endothelial dysfunction (ED) and impaired cognition. Adjuvant-induced arthritis (AIA) in rats was used as a model of RA. Clinical inflammatory symptoms were evaluated from an arthritis score and brains were collected at day 31 ± 2 post-immunization. Neuronal expression of BDNF and TrkB phosphorylated at tyrosine 816 (p-TrkB) was examined in brain slices. Endothelial BDNF and p-TrkB expression was examined on both brain slices (hippocampal arterioles) and isolated cerebral microvessels-enriched fractions (vessels downstream to arterioles). The connection between endothelial nitric oxide (NO) and BDNF production was explored on the cerebrovascular fractions using endothelial NO synthase (eNOS) levels as a marker of NO production, Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) as a NOS inhibitor and glyceryl-trinitrate as a slow releasing NO donor. Brain slices displayed lower BDNF and p-TrkB staining in both neurons and arteriolar endothelial cells in AIA than in control rats. For endothelial cells but not neurons, a strong correlation was observed between BDNF and p-TrkB staining. Of note, a strong correlation was also observed between neuronal p-TrkB and endothelial BDNF staining. In cerebral microvessels-enriched fractions, AIA led to decreased BDNF and eNOS levels with a positive association between the 2 parameters. These effects coincided with decreased BDNF and p-TrkB staining in endothelial cells. The exposure of AIA cerebrovascular fractions to GTN increased BDNF levels while the exposure of control fractions to L-NAME decreased BDNF levels. Changes in the cerebral BDNF pathway were not associated with arthritis score. The present study reveals that AIA impairs the endothelial and neuronal BDNF/TrkB pathway, irrespective of the severity of inflammatory symptoms but dependent on endothelial NO production. These results open new perspectives for the understanding of the link between ED and impaired cognition.

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“…Previous studies have shown that patients with substance use disorder usually exhibit decreased inhibitory response on the Stroop test (Hillman & Drobes, 2012), and that an acute session of aerobic exercise improves the performance on inhibitory control associated with greater activity on electrophysiological records of the PFC (Wang, Zhou, Zhao, Wu, & Chang, 2016). Interestingly, exercise has been related to increased levels of brain-derived neurotrophic factor, which plays an important role on several molecular changes that might enhance cognitive functions (Monnier et al, 2017). In addition, exercise has also been shown to improve neurogenesis (van Praag, 2008).Taken together, these PFC and cognitive improvements are extremely important to this individual, because it might lead to greater impulsivity control and abstinence maintenance, thereby decreasing the negative effects on cognitive functions induced by chronic drug intake.…”

Section: Discussionmentioning

confidence: 99%

The Benefits of High Intensity Exercise on the Brain of a Drug Abuser

Cabral¹,

Tavares²,

Costa³

et al. 2018

GJHS

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Chronic drug abuse has been shown to cause dysfunctions on the frontal lobe and affect cognition, cardiac autonomic control and psychosocial aspects. Despite physical exercise has been shown to improve cerebral functioning, the effects of a high intensity exercise training program needs to be further explored in a drug abuse condition. The patient was a 32-year-old male who has been an alcohol and crack/cocaine user for 20 years. The high intensity exercise training protocol consisted of four 30-second "all-out" bouts performed three times per week during four weeks. The participant had electroencephalographic (EEG) activity, cognition, cardiac autonomic control and psychosocial questionnaires evaluated before and after high intensity exercise training. Prefrontal cortex (PFC) oxygenation during an incremental running exercise test was also recorded. EEG topographical analysis revealed greater PFC activation during the cognitive test. Performance on the cognitive test was enhanced (l number of total errors and reaction time). Parasympathetic cardiac indices, including RMSSD, SDNN, Pnn50% and HF power increased by 77.4%, 83.3%, 57.7% and 293.2%, respectively. Sleep quality increased 23% and anxiety levels decreased 52.6%. Psychological and social domains increased 5.3% and 13.7%, respectively. In addition, incremental treadmill running time increased 12.5% and PFC oxyhemoglobin increased 228.2% at the beginning of the treadmill test, 305.4% at the middle and 359.4% at the end of the test. Thus, high intensity exercise training improved PFC functioning, cardiac autonomic control and psychological parameters. These results might indicate high intensity exercise as an alternative and non-pharmacological tool to help the rehabilitation of a drug abuser.

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Effect of short-term exercise training on brain-derived neurotrophic factor signaling in spontaneously hypertensive rats

Abstract: Our results revealed that endothelial and neuronal BDNF expressions were both impaired in hypertension and that physical exercise improved hippocampal mBDNF levels and signaling through blood pressure-independent mechanisms.

Cited by 20 publications

References 56 publications

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

Vascular and cerebral benefits of Tofacitinib in rheumatoid arthritis: evidence in rat adjuvant-induced arthritis

The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or Endothelial, Is Impaired in Rats with Adjuvant-Induced Arthritis. Connection with Endothelial Dysfunction

The Benefits of High Intensity Exercise on the Brain of a Drug Abuser

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