Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats

Souza, Leonardo C.; Martynhak, Bruno Jacson; Bassani, Taysa Bervian; Turnes, Joelle de Melo; Machado, Meira Maria Forcelini; Moura, Eric Luiz Rossa; Andreatini, Roberto; Vital, Maria A.B.F.

doi:10.1016/j.physbeh.2018.02.033

Cited by 17 publications

(11 citation statements)

References 66 publications

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“…The tendency to decrease the activity during the dark phase in response to 6-OHDA was also in accordance with other studies, some of them suggested that 6-OHDA-lesioned rats may show slightly motor impairment and more diurnal activity during the first week after 6-OHDA administration into the SN ( Souza et al, 2018 ). While other studies did not detect activity change during the light phase ( Masini et al, 2017 ).…”

Section: Discussionsupporting

confidence: 90%

“…Thus, the dopamine depletion did not reach the required threshold to develop motor symptoms ( Deumens et al, 2002 ; Padmanabhan and Burke, 2018 ). However, this loss of dopamine could be sufficient to induce disruption of the circadian rhythms contrary to other studies which suggested a higher dopaminergic neuronal loss (about 60%) in order to detect disruption of circadian locomotor ( Souza et al, 2018 ). In addition, results indicated that a selective vulnerability to the toxin could be observed, pointing out to a dopamine decline topologically distributed in the SN, in concordance with our previous works ( Requejo et al, 2015 , 2017 ).…”

Section: Discussioncontrasting

confidence: 72%

“…Thus, we can speculate that this change in the pattern of rest/activity seen in response to 6-OHDA may be similar to the insomnia at night or the hypersomnia during the daytime experimented by PD patients ( De Castro Medeiros et al, 2019 ). Behavioral changes related to circadian cycles were already described in the 6-OHDA model, such as alterations on circadian locomotor rhythm parameters ( Ben and Bruguerolle, 2000 ; Gravotta et al, 2011 ; Masini et al, 2017 ; De Lazzari et al, 2018 ; Souza et al, 2018 ; Ciric et al, 2019 ; De Castro Medeiros et al, 2019 ). In fact, some of these studies associated the circadian disruption with the loss of dopaminergic neurons indicating that dopamine may act as a modulator of the circadian system ( Isobe and Nishino, 2001 ; Gravotta et al, 2011 ; De Lazzari et al, 2018 ; Souza et al, 2018 ; Ciric et al, 2019 ; De Castro Medeiros et al, 2019 ).…”

Section: Discussionmentioning

confidence: 93%

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Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson’s Disease: Exploring Prodromal Biomarkers

et al. 2020

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The search for experimental models mimicking an early stage of Parkinson’s disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA ( n = 10) or saline solution ( n = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.

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Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 93%

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Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson’s Disease: Exploring Prodromal Biomarkers

et al. 2020

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“…The tendency to decrease the activity during the dark phase in response to 6-OHDA was also in accordance with other studies, some of them suggested that 6-OHDA-lesioned rats may show slightly motor impairment and more diurnal activity during the rst week after 6-OHDA administration into the SN [24]. While other studies did not detect activity change during the light phase [25].…”

Section: Discussionsupporting

confidence: 90%

Changes in day/night activity in the 6-OHDA-induced experimental model of Parkinson´s disease: Exploring prodromal biomarkers

Requejo

de-Ipiña

Ruiz-Ortega

et al. 2020

Preprint

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Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder for which there is not currently a cure and when it is clinically diagnosed is likely too late. The search for experimental models mimicking an early stage of PD before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Methods: Rats were unilaterally injected with 6-OHDA or saline solution into the striatum and placed in enriched environment cages where the activity was monitored. After two weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Results: Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase respectively turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Conclusions: Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.

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“…Sousa ve ark. (22) 6-OHDA intranigral modelinde, lokomotor aktivitesinin sirkadiyen ritimlerindeki olası bozuklukları araştırmışlardır. Hayvanların 22 gün boyunca agomelatin 50 mg/kg ile tedavi edilmesi, sirkadiyen ritim parametrelerinde ve nöroproteksiyonda önemli değişiklikler yaratmamıştır.…”

Section: Discussionunclassified

Agomelatin’s Effect on Parkinson Disease Model on Rats

Soner¹,

Ayvat²,

Şahin³

2019

BUCH

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Parkinson hastalığı en sık görülen nörodejeneratif hastalıklardan biridir. Günümüzde hastalığın tam tedavisi bulunmamaktadır. Agomelatin pineal bezde sentezlenip salıverilen melatonin hormonunun sentetik analoğudur; merkezi sinir sistemindeki (MSS) antidepresan etkilerini melatonin kaynaklı MT1 ve MT2 reseptörlerini aktive ederek, monoamin kaynaklı serotonin 5-HT2C reseptörlerini antagonize ederek gösterir. Çalışmamızda, oral Agomelatin uygulamasının sıçanlarda 6-OHDA ile oluşturulan deneysel Parkinson hastalığı üzerine etkilerini araştırdık. Yöntem: Bu amaçla 270-330 g aralığında üç gruptaki 45 sıçana unilateral intrastriatal 6-OHDA uygulandı. Kontrol grubuna çözücü, tedavi gruplarına ise 5 mg/kg/gün ve 20 mg/kg/gün Agomelatin tedavisi 15 gün süre ile uygulandı. Bu süre sonunda motor koordinasyon ve beceriler yapışkan bant testi, açık alan testi ve silindir testi ile değerlendirilirken, dopaminerjik hasar derecesi apomorfin ile indüklenen dönme testi ile değerlendirildi. Bulgular: Çalışmamızda, her iki dozda uygulanan Agomelatinin, (5 mg/kg ve 20 mg/kg) 6-OHDA aracılı oluşturulan deneysel Parkinson hastalığında progresyonu önlediğini saptadık. Sonuç: Agomelatin deneysel Parkinson hastalığı modelinde striatal nöronlardaki hasar üzerine koruyucu etki göstermiştir.

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Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats

Cited by 17 publications

References 66 publications

Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson’s Disease: Exploring Prodromal Biomarkers

Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson’s Disease: Exploring Prodromal Biomarkers

Changes in day/night activity in the 6-OHDA-induced experimental model of Parkinson´s disease: Exploring prodromal biomarkers

Agomelatin’s Effect on Parkinson Disease Model on Rats

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