Transcranial direct current stimulation ameliorates motor and cognitive functions by regulating neuronal excitotoxicity in experimental Parkinson’s disease model

Güven Akçay; Serhan Tamerer

doi:10.17826/cumj.1322361

EN TR

Transcranial direct current stimulation ameliorates motor and cognitive functions by regulating neuronal excitotoxicity in experimental Parkinson’s disease model

Abstract

Purpose: In the study, the therapeutic effects of early and long-term transcranial direct current stimulation (tDCS) in Parkinson's disease (PD) rats with 6-hydroxydopamine (6-OHDA) lesions of tDCS were investigated. Materials and Methods: After early and prolonged tDCS administration in PD animals (starting 24 hours after PD lesion, 1000 mA anodal tDCS, 30 min/day, 13 days), the effects of tDCS on motor and cognitive function behaviors and glutamatergic neuron excitotoxicity were determined by Ca2+, glutamate, and NMDAR1 levels. Results: We found that the 13-day tDCS intervention significantly reduced 6-OHDA-induced motor deficits in locomotor activity, learning, and memory-like behavior. Biochemically, we showed that it also reduces Ca2+, glutamate, and NMDAR1 levels, which cause hippocampal neuronal damage. Conclusion: These results suggest that early and long-term tDCS may exert neuroprotective effects and reduce the exacerbation of motor and cognitive impairments in a rat model of 6-OHDA-induced PD. However, it also shows that tDCS has an effect on the glutamatergic pathway in PD and prevents neuronal excitotoxicity. Furthermore, this preclinical model may increase the potential use of therapeutic tDCS and serve as a translation platform to further define the therapeutic mechanism of tDCS for PD or other disorders.

Keywords

Learning , Locomotor Activity , Neuroprotective Treatment , Parkinson , Transcranial Direct Current Stimulation

Transkraniyal doğru akım stimülasyonu deneysel Parkinson hastalığı modelinde nöronal eksitotoksisiteyi düzenleyerek motor ve bilişsel işlevleri iyileştirir

Öz

Amaç: Bu çalışmada, 6-hidroksidopamin (6-OHDA) Parkinson hastalığı (PH) sıçanlarında erken ve uzun süreli transkraniyal doğru akım stimülasyonunun (tDAS= terapötik etkileri araştırılmıştır. Gereç ve Yöntem: PH hayvanlarında erken ve uzun süreli tDAS uygulamasından sonra (PH lezyonundan 24 saat sonra başlayarak, 1000 mA anodal tDCS, 30 dakika/gün, 13 gün), tDAS'nin motor ve bilişsel fonksiyon davranışları ve glutamaterjik nöron eksitotoksisitesi üzerindeki etkileri Ca2+, glutamat ve NMDAR1 seviyeleri ile belirlendi. Bulgular: 13 günlük tDAS tedavisi lokomotor aktivite, öğrenme ve hafıza benzeri davranışlarda 6-OHDA kaynaklı motor bozuklukları önemli ölçüde azalttığı görüldü. Biyokimyasal olarak, hipokampal nöronal hasara neden olan Ca2+, glutamat ve NMDAR1 seviyelerini de azalttığı gözlendi. Sonuç: Bu sonuçlar, erken ve uzun süreli tDAS'nin nöroprotektif etkiler gösterebileceğini ve 6-OHDA ile indüklenen PH sıçan modelinde motor ve bilişsel bozuklukların artmasını azaltabileceğini göstermektedir. Bununla birlikte, tDAS'ın PH'de glutamaterjik yolak üzerinde etkisi olduğunu ve nöronal eksitotoksisiteyi önlediğini de göstermektedir. Ayrıca, bu preklinik model terapötik tDAS'nin potansiyel kullanımını arttırabilir ve PH veya diğer bozukluklar için tDAS'nin terapötik mekanizmasını daha fazla açıklamak için bir tedavi yöntemi olabilir.

Anahtar Kelimeler

Öğrenme , lokomotor aktivite , nöroprotektif tedavi , Parkinson hastalığı , transkraniyal doğru akım stimülasyonu

Kaynakça

Foffani G, Obeso JA. A cortical pathogenic theory of Parkinson’s disease. Neuron. 2018;99:1116-28.
Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci. 2017;18:101-13.
Weintraub D, Stern MB. Psychiatric complications in Parkinson disease. Am J Geriatr Psychiatry. 2005;13:844-51.
Chen JJ, Swope DM. Pharmacotherapy for Parkinson's disease. Pharmacotherapy. 2007;27:161-73.
Delgado M, Ganea D. Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation. The FASEB journal. 2003;17:1-18.
Casetta I, Govoni V, Granieri E. Oxidative stress, antioxidants and neurodegenerative diseases. Curr Pharm Des.. 2005;11:2033-52.
Dipasquale B, Marini AM, Youle RJ. Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons. Biochem Biophys Res Commun. 1991;181:1442-8.
Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology. 2007;69:1836-42.
Yıgıt G, Arıcıoglu F. Günümüz ve gelecekte Parkinson Hastalığı için farmakolojik Tedavi yaklaşımları. Clinical and Experimental Health Sciences. 2015;5:265-73.
Nakanishi S, Masu M. Molecular diversity and functions of glutamate receptors. Annu Rev Biophys Biomol Struct. 1994;23:319-48.

Dong X-x, Wang Y, Qin ZH. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin. 2009;30:379-87.
Masilamoni GJ, Smith Y. Metabotropic glutamate receptors: targets for neuroprotective therapies in Parkinson disease. Curr Opin Pharmacol. 2018;38:72-80.
Pfeiffer RF. Parkinson disease: calcium channel blockers and Parkinson disease. Nat Rev Neurol. 2010;6:188-9.
Carrillo-Mora P, Silva-Adaya D, Villaseñor-Aguayo K. Glutamate in Parkinson's disease: Role of antiglutamatergic drugs. Basal Ganglia. 2013;3:147-57.
Conn PJ, Pin J-P. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol. 1997;37:205-37.
Kanai Y, Smith CP, Hediger MA. The elusive transporters with a high affinity for glutamate. Trends Neurosci. 1993;16:365-70.
Olney J, Ho OL, Rhee V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res. 1971;14:61-76.
Lau A, Tymianski M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch. 2010;460:525-42.
Karki P, Lee E, Aschner M. Manganese neurotoxicity: a focus on glutamate transporters. Ann Occup Environ Med.. 2013;25:1-5.
Benninger DH, Lomarev M, Lopez G, Wassermann EM, Li X, Considine E et al. Transcranial direct current stimulation for the treatment of Parkinson's disease. J Neurol Neurosurg Psychiatry. 2010;81:1105-11.
Purpura DP, McMurtry JG. Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol.. 1965;28:166-85.
Webster BR, Celnik PA, Cohen LG. Noninvasive brain stimulation in stroke rehabilitation. NeuroRx. 2006;3:474-81.
Bashir S, Yoo W-K. Neuromodulation for addiction by transcranial direct current stimulation: opportunities and challenges. Ann Neurosci. 2016;23:241-5.
Stagg CJ, Antal A, Nitsche MA. Physiology of transcranial direct current stimulation. J ECT. 2018;34:144-52.
Sinen O, Bülbül M, Derin N, Ozkan A, Akcay G, Aslan MA et al. The effect of chronic neuropeptide-S treatment on non-motor parameters in experimental model of Parkinson's disease. Int J Neurosci. 2021;131:765-74.
Akcay G, Derin N. The effects of tDCS on depression and anxiety disorders induced by sub-chronic stress. Turk Hij Den Biyol Derg. 2022;79:267-78.
Akcay G, Nemutlu Samur D, Derin N. Transcranial direct current stimulation alleviates nociceptive behavior in male rats with neuropathic pain by regulating oxidative stress and reducing neuroinflammation. J Neurosci Res. 2023;101:1457-70.
Akcay G. Therapeutic effects of transcranial direct current stimulation on ketamine-induced schizophrenia-like behaviors and oxidative stress. Med Science. 2023;12:63-9.
Feng XJ, Huang YT, Huang YZ, Kuo CW, Peng CW, Rotenberg A et al. Early transcranial direct current stimulation treatment exerts neuroprotective effects on 6-OHDA-induced Parkinsonism in rats. Brain Stimul. 2020;13:655-63..
Li Y, Tian X, Qian L, Yu X, Jiang W. Anodal transcranial direct current stimulation relieves the unilateral bias of a rat model of Parkinson's disease. Annu Int Conf IEEE Eng Med Biol Soc. 2011:765-8.
Winkler C, Reis J, Hoffmann N et al. Anodal transcranial direct current stimulation enhances survival and integration of dopaminergic cell transplants in a rat parkinson model. eNeuro. 2017;4.
Lee SB, Youn J, Jang W, Yang HO. Neuroprotective effect of anodal transcranial direct current stimulation on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice through modulating mitochondrial dynamics. Neurochem Int. 2019;129:104491.
Lu C, Wei Y, Hu R, Wang Y, Li K, Li X. Transcranial direct current stimulation ameliorates behavioral deficits and reduces oxidative stress in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of parkinson's disease. Neuromodulation 2015;18:442-6.
Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron. 2010;66:198-204.
Leffa DT, Bellaver B, Salvi AA, de Oliveira C, Caumo W, Grevet EH et al. Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters. Brain Stimul. 2018;11:743-51.
Jiang T, Xu RX, Zhang AW, Di W, Xiao ZJ, Miao JY et al. Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction. Neuroscience. 2012;226:421-6.
Yoon KJ, Lee YT, Chae SW, Park CR, Kim DY. Effects of anodal transcranial direct current stimulation (tDCS) on behavioral and spatial memory during the early stage of traumatic brain injury in the rats. J Neurol Sci. 2016;362:314-20.
Feng XJ, Huang YT, Huang YZ, Kuo CW, Peng CW, Rotenberg A et al. Early transcranial direct current stimulation treatment exerts neuroprotective effects on 6-OHDA-induced Parkinsonism in rats. Brain Stimul. 2020;13:655-63.
Chen M, Wang Y, Liu Y, Hou XY, Zhang QG, Meng FJ et al. Possible mechanisms underlying the protective effects of SY-21, an extract of a traditional Chinese herb, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampus. Brain Res. 2003;989:180-6.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Klinik Tıp Bilimleri (Diğer) , Merkezi Sinir Sistemi

Bölüm

Araştırma Makalesi

Yazarlar

Güven Akçay ^*
0000-0003-3418-8825
Türkiye

Serhan Tamerer Bu kişi benim
0009-0005-9795-455X
Türkiye

Erken Görünüm Tarihi

25 Eylül 2023

Yayımlanma Tarihi

30 Eylül 2023

Gönderilme Tarihi

5 Temmuz 2023

Kabul Tarihi

8 Eylül 2023

Yayımlandığı Sayı

Yıl 2023 Cilt: 48 Sayı: 3

DOI

https://doi.org/10.17826/cumj.1322361

IZ

https://izlik.org/JA36FA36PZ

MLA

Akçay, Güven, ve Serhan Tamerer. “Transcranial direct current stimulation ameliorates motor and cognitive functions by regulating neuronal excitotoxicity in experimental Parkinson’s disease model”. Cukurova Medical Journal, c. 48, sy 3, Eylül 2023, ss. 919-28, doi:10.17826/cumj.1322361.