Cardiovascular evaluation of female rats with 6-OHDA-induced parkinsonism: Possible protection by ovarian hormones and participation of nitric oxide

Campos, Blenda Hyedra de; Jager, Lorena de; Reginato, Gabriela de Souza; Pereira, Rito Santo; Crestani, Carlos C.; Pinge‐Filho, Phileno; Martins‐Pinge, Marli Cardoso

doi:10.1016/j.lfs.2020.118259

Cited by 7 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results were observed using the 6-OHDA model in males (12), where HRV decreased compared to controls. However, in some animal studies using low doses, this reduction in HRV has not been observed in males (32) and females (21). The present study is the first to test the effect of a high dose of 6-OHDA in females, and we did not observe any effect in the time (Figure 2) or frequency domain analyses (Figure 3).…”

Section: ' Discussioncontrasting

confidence: 41%

“…Compared with males, females have a higher vagal tone; however, this difference appears to wear off after menopause (33). Estrogen increases vagal tone in male and female rodents (34), and ovariectomy appears to increase the sympathetic activity after the surgery (35), but this effect was no longer observed 14 (21) and 21 (36,37) days after ovariectomy. These differences in autonomic function response to ovariectomy could be explained not only as an adaptation mechanism of the system to new hormonal levels but also as an effect of steroidal hormone production by other tissues, such as the adrenal glands, the adipose tissue, or even the brain.…”

Section: ' Discussionmentioning

confidence: 99%

“…The authors of this study named this phenomenon as the ''critical period for nigrostriatal neuroprotection,'' suggesting that in the 6-OHDA model, the physiological neuroprotection provided by sex hormones is time-dependent, both under physiological and supplemented conditions. Some studies have already explored the participation of sex hormones in cardiovascular and autonomic function in PD, using the 6-OHDA model and ovariectomized rats with hormonal treatment (21). However, to date, this is the first study to use a high dose of 6-OHDA, which, according to the literature, causes a high autonomic impairment in males.…”

Section: ' Introductionmentioning

confidence: 99%

See 2 more Smart Citations

6-hydroxydopamine and ovariectomy has no effect on heart rate variability parameters of females

Rosa

Calvo

Gonçalves

et al. 2021

Clinics

View full text Add to dashboard Cite

In addition to the classic motor symptoms of Parkinson's disease (PD), patients also present with non-motor symptoms, such as autonomic dysfunction, which is present in almost 90% of patients with PD, affecting the quality of life and mortality. Regarding sex differences in prevalence and presentation, there is increasing concern about how sex affects autonomic dysfunction. However, there are no previous data on autonomic cardiac function in females after 6-hydroxydopamine (6-OHDA) striatal injection. METHODS: Wistar female rats were ovariectomized. After 20 days, the animals received bilateral injections of 6-OHDA (total dose per animal: 48 mg) or a vehicle solution in the striatum. Thirty days after 6-OHDA injection, subcutaneous electrodes were implanted for electrocardiogram (ECG) recording. Ten days after electrode implantation, ECG signals were recorded. Analyses of heart rate variability (HRV) parameters were performed, and the 6-OHDA lesion was confirmed by analyzing the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta (SNpc). RESULTS: A high dose of 6-OHDA did not affect HRV of females, independent of ovariectomy. As expected, ovariectomy did not affect HRV or lesions in the SNpc after 6-OHDA injection. CONCLUSIONS: We suggest that females with 6-OHDA present with cardioprotection, independent of ovarian hormones, which could be related to female vagal predominance.

show abstract

Section: ' Discussioncontrasting

confidence: 41%

Section: ' Discussionmentioning

confidence: 99%

Section: ' Introductionmentioning

confidence: 99%

See 1 more Smart Citation

6-hydroxydopamine and ovariectomy has no effect on heart rate variability parameters of females

Rosa

Calvo

Gonçalves

et al. 2021

Clinics

View full text Add to dashboard Cite

show abstract

“…Interestingly, ovarian hormones seem to have a cardiac protective role against intracranial 6-OHDA intoxication in rats [151]. Males bilaterally infused in the SNpc with 6-OHDA showed a decreased mean arterial pressure and heart rate, and increased nitric oxide (NO) levels in the heart and aorta compared to sham animals [69,152].…”

Section: Experimental Models Of Parkinsonismmentioning

confidence: 99%

Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence

Cuenca‐Bermejo

Almela

Navarro‐Zaragoza

et al. 2021

IJMS

View full text Add to dashboard Cite

Dysautonomia is a common non-motor symptom in Parkinson’s disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads to cardiovascular dysfunction, which is highly prevalent in PD patients. Cardiac alterations such as orthostatic hypotension, heart rate variability, modifications in cardiogram parameters and baroreflex dysfunction can appear in both the early and late stages of PD, worsening as the disease progresses. In PD patients it is generally found that parasympathetic activity is decreased, while sympathetic activity is increased. This situation gives rise to an imbalance of both tonicities which might, in turn, promote a higher risk of cardiac damage through tachycardia and vasoconstriction. Cardiovascular abnormalities can also appear as a side effect of PD treatment: L-DOPA can decrease blood pressure and aggravate orthostatic hypotension as a result of a negative inotropic effect on the heart. This unwanted side effect limits the therapeutic use of L-DOPA in geriatric patients with PD and can contribute to the number of hospital admissions. Therefore, it is essential to define the cardiac features related to PD for the monitorization of the heart condition in parkinsonian individuals. This information can allow the application of intervention strategies to improve the course of the disease and the proposition of new alternatives for its treatment to eliminate or reverse the motor and non-motor symptoms, especially in geriatric patients.

show abstract

“…Parkinson's disease (PD), which is one of the most common neurodegenerative diseases in the aging population, is characterized by the progressive and selective destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the brain (Tysnes and Storstein, 2017;de Campos et al, 2020;Jayaraj et al, 2020). Although the etiology of the disease remains unknown, accumulating evidence shows that neuroinflammation and mitochondrial dysfunction are common features of PD pathology, and recent studies have identified an important role for the adaptive immune system in the development of PD (Harms et al, 2017;Manocha et al, 2017;Park et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of the α7 Nicotinic Receptor Agonist PNU-282987 on Dopaminergic Neurons Against 6-Hydroxydopamine, Regulating Anti-neuroinflammatory and the Immune Balance Pathways in Rat

Jiang

Wang

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neuroinflammation and inner immune dysfunction are increasingly accepted as important components of the etiopathogenesis of Parkinson’s disease (PD). According to emerging evidence, a7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel, plays an important role in inflammatory reactions and is also expressed on the surface of T cells. In particular, regulatory T cells (Tregs) are critical for the maintenance of immunological tolerance. In the present study, we investigated the roles of α7nAChR in inhibiting inflammation and maintaining the immune balance in rats with 6-hydroxydopamine (6-OHDA)-induced lesions and the possible mechanisms regulating the proportion of Tregs in vivo. Adult male Wistar rats (n = 90) were subjected to a unilateral injection of 6-OHDA into the left medial forebrain bundle, and PNU-282987, an α7nAChR agonist, was intraperitoneally injected 2 h prior to the induction of lesions by 6-OHDA and again at days 1, 7, and 13 postlesion. Behavioral tests and immunohistochemical staining to detect the expression of tyrosine hydroxylase (TH) in the bilateral substantial nigra (SN) were performed. Subsequently, CD4+ T lymphocytes and the expression of forkhead/winged helix transcription factor p3 (Foxp3, which is a marker of Treg cells) in the SN were also assessed using immunofluorescence staining. The expression of glial fibrillary acidic protein (GFAP) in the SN was determined by performing immunohistochemical staining. Additionally, the protein levels of α7nAChR, extracellular signal-regulated kinase (Erk) phosphorylated-Erk (p-Erk) and Foxp3 in the ventral midbrain were determined using Western blotting, and the relative expression of the TNF-α, IL-1β, and IL-10 mRNAs were detected using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). We found that PNU-282987 significantly improved the motor deficits induced by 6-OHDA, reduced the loss of TH in the SN, suppressed the overactivation of GFAP+ cells and expression of related inflammatory cytokines, and increased the number of Foxp3+ cells. In addition, we also showed that PNU-282987 significantly increased the protein expression of the a7nAchR, p-Erk, and Foxp3 in 6-OHDA-lesioned rats (p < 0.05). These results indicated that α7nAChR activation could exert an anti-inflammatory effect and participate in the process of modulating the immune balance during 6-OHDA-induced injury, potentially through the α7nAChR/p-Erk/Foxp3 signaling pathway.

show abstract

Cardiovascular evaluation of female rats with 6-OHDA-induced parkinsonism: Possible protection by ovarian hormones and participation of nitric oxide

Cited by 7 publications

References 33 publications

6-hydroxydopamine and ovariectomy has no effect on heart rate variability parameters of females

6-hydroxydopamine and ovariectomy has no effect on heart rate variability parameters of females

Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence

Protective Effect of the α7 Nicotinic Receptor Agonist PNU-282987 on Dopaminergic Neurons Against 6-Hydroxydopamine, Regulating Anti-neuroinflammatory and the Immune Balance Pathways in Rat

Contact Info

Product

Resources

About