Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb

Sasajima, Hitoshi; Miyazono, Sadaharu; Noguchi, Tetsuya; Kashiwayanagi, Makoto

doi:10.1016/j.neuro.2015.10.006

Cited by 32 publications

(28 citation statements)

References 49 publications

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“…In addition, the striatum and the SNr were also stained with anti-TH antibody depending on the axonal projections from the DA neurons in the SNpc. 16) Similar to the previous results obtained in mice one week after intranasal rotenone administration, 14) TH-positive signals in the OB were diminished by rotenone administration (Fig. 1B).…”

Section: Resultssupporting

confidence: 89%

“…To prevent hydrolytic degradation, the rotenone stock solution was diluted with water just before administration to mice. As described previously, 14) a rotenone dilution (rotenone: 0.35 mg/kg; DMSO: 9.86 mg/kg) or vehicle (DMSO: 9.86 mg/kg) was injected into the right-side nasal cavity of mice. These single administrations were given once a day for 2 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…14) A 20-µL aliquot of butyric acid (undiluted or with 25% diluent) or water absorbed in a piece of filter paper in a petri dish was placed at the end of each short arm of the maze. Clean air was supplied from the end of each short arm to the end of the long arm.…”

Section: Methodsmentioning

confidence: 99%

“…13) We used one-week rotenone administration to the nasal cavity of mice to mimic inhalation exposure to an environmental neurotoxin, and found that the number of DA neurons in the OB was decreased and the olfactory function attenuated by this treatment. 14) Olfactory discrimination deficits in mice lacking the D2 dopaminergic receptor suggest that decreases in DA neurons in the OB also could induce olfactory dysfunctions. 12) However, it has not been ascertained whether the influence of intranasally administered rotenone is limited to the OB.…”

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confidence: 99%

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Intranasal Administration of Rotenone to Mice Induces Dopaminergic Neurite Degeneration of Dopaminergic Neurons in the Substantia Nigra

Sasajima

Miyazono

Noguchi

et al. 2017

Biological & Pharmaceutical Bulletin

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Exposure to environmental neurotoxins is suspected to be a risk factor for sporadic progressive neurodegenerative diseases. Parkinson's disease has been associated with exposure to the pesticide rotenone, a mitochondrial respiration inhibitor. We previously reported that intranasal administration of rotenone in mice induced dopaminergic (DA) neurodegeneration in the olfactory bulb (OB) and reduced olfactory functions. In the present study, we investigated the DA neurons in the brains of mice that were administered rotenone intranasally for an extended period. We found that the olfactory function of mice was attenuated by rotenone administration. Electrophysiological analysis of the mitral cells, which are output neurons in the OB, revealed that the inhibitory input into the mitral cells was retarded. In the immunohistochemical analysis, neurite degeneration of DA neurons in the substantia nigra was observed in rotenone-administered mice, indicating that rotenone progressively initiated the degeneration of cerebral DA neurons via the nasal route.Key words dopaminergic neuron; intranasal administration; olfactory bulb; rotenone; substantia nigra Environmental chemicals are suspected to be risk factors for neurodegenerative diseases.1) One case control study indicated an association between Parkinson's disease (PD) and the use of a group of pesticides that inhibit mitochondrial complex I, which included rotenone and paraquat.2) PD is characterized by degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc).3) DA neurons are vulnerable to reactive oxygen species (ROS) generated by aberrant mitochondrial respiration.4) Subcutaneous chronic infusion or direct brain infusion of rotenone induces DA neurodegeneration in the substantia nigra (SN) and features of PD in rats, suggesting that exposure to neurotoxins such as rotenone is a risk factor for PD. 5,6) In general, exposure of the human brain to environmental chemicals occurs following the intake of such chemicals by ingestion, cutaneous contact, or inhalation. Various chemicals absorbed at the olfactory mucosa reach the brain directly through passive diffusion from the extra-neural space of olfactory nerves to the cerebrospinal fluid and/or by the active axonal transport of olfactory neurons. 7,8) Prediger et al. postulated that some forms of PD may be caused by environmental agents delivered to the brain via the olfactory mucosa. 9)PD patients often suffer dysosmia as their first symptom. 10)In the olfactory bulb (OB), a primary center for olfactory information processing, DA neurons function as inhibitory interneurons increasing the dynamic range of information transfer from olfactory receptor neurons to OB neurons 11) and maintaining the odor discriminating ability.12) Huisman et al. reported that DA neurons in the OB increased in postmortem autopsy of PD patients, suggesting an increase in inhibitory inputs of dopamine into olfactory nerve terminals could reduce olfactory functions.13) We used one-week rotenone administration to th...

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Section: Resultssupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Intranasal Administration of Rotenone to Mice Induces Dopaminergic Neurite Degeneration of Dopaminergic Neurons in the Substantia Nigra

Sasajima

Miyazono

Noguchi

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Так, при аутопсийных исследованиях в ОЛ пациентов с БП обнаружены синуклеинпозитивные патологические агрегаты и уменьшение размеров обонятельных клубочков (гломерул) [10,11]. В эксперименте интраназальное введение нейротоксических индукторов паркинсонизма вызывало накопление α-Syn, деструкцию и дисфункцию перигломерулярных дофаминовых нейронов в ОЛ и повреждение черной субстанции [12,13]. В то же время разрушение черной субстанции у животных, согласно ряду авторов, приводит к нарушению миграции дофаминовых нейронов, а их количество в ОЛ увеличивается [14,15].…”

Section: Introductionunclassified

Alpha-synuclein detection in olfactory mouse bulbs in ontogenesis in vivo and in the organotypic culture

Воронков¹,

Lyzhin²,

Kapkaeva³

et al. 2019

Clin. Exp. Morphology

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Выявление альфа-синуклеина в обонятельных луковицах мыши в онтогенезе in vivo и в органотипической культуре Д.Н. Воронков, А.А. Лыжин, М.Р. Капкаева, Р.М. Худоерков, Л.Г. Хаспеков ФГБНУ Научный центр неврологии, Москва, Россия Введение. Агрегация альфа-синуклеина (a-Syn) считается причиной нейродегенерации при болезни Паркинсона. Накопление и агрегация a-Syn в обонятельных луковицах (ОЛ) предположительно приводят к нарушениям обоняния при паркинсонизме. Вместе с тем функция a-Syn и его локализация в ОЛ в норме требуют уточнения. Цель исследования -охарактеризовать распределение a-Syn в онтогенезе ОЛ и оценить адекватность культивирования эксплантатов ОЛ как модельной системы для изучения патогенеза болезни Паркинсона. Материалы и методы. Исследовали обонятельные луковицы эмбрионов беспородных мышей на 17-й и 19-й день внутриутробного развития и у новорожденных мышей в возрасте 2 и 7 дней. Экспланты ОЛ мышей 17-го эмбрионального дня и 2-го постнатального дня культивировали 24 часа в роллерной установке. Иммуногистохимическим методом исследовали локализацию a-Syn, синаптофизина и тирозингидроксилазы в обонятельных луковицах. Результаты. Экспрессия a-Syn, синаптофизина и тирозингидроксилазы обнаруживалась в периферических слоях обонятельных луковиц и менялась по мере их созревания, однако локализация этих белков совпадала лишь частично. На 2-й день постнатального развития a-Syn выявляли в телах и отростках нейронов митрального слоя и в обонятельных клубочках. К 7-му дню a-Syn выявлялся преимущественно в пресинаптических окончаниях в обонятельных клубочках. В органотипической культуре организация ОЛ соответствовала их нативной структуре. Выводы. Экспрессия α-Syn в развивающихся ОЛ связана с формированием обонятельных клубочков и созреванием клеток митрального слоя, а его распределение в норме согласуется с особенностями вовлечения обонятельных структур в нейродегенеративный процесс при болезни Паркинсона. Полученные данные демонстрируют возможность использования органотипических культур ОЛ для моделирования патологических процессов при болезни Паркинсона. Ключевые слова: альфа-синуклеин, обонятельные луковицы, онтогенез, органотипическая культура. Для корреспонденции: Дмитрий Николаевич Воронков.

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The protective effect of inosine against rotenone-induced Parkinson’s disease in mice; role of oxido-nitrosative stress, ERK phosphorylation, and A2AR expression

El-Shamarka

Kozman

Messiha

2020

Naunyn-Schmiedeberg's Arch Pharmacol

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Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb

Cited by 32 publications

References 49 publications

Intranasal Administration of Rotenone to Mice Induces Dopaminergic Neurite Degeneration of Dopaminergic Neurons in the Substantia Nigra

Intranasal Administration of Rotenone to Mice Induces Dopaminergic Neurite Degeneration of Dopaminergic Neurons in the Substantia Nigra

Alpha-synuclein detection in olfactory mouse bulbs in ontogenesis in vivo and in the organotypic culture

The protective effect of inosine against rotenone-induced Parkinson’s disease in mice; role of oxido-nitrosative stress, ERK phosphorylation, and A2AR expression

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