Effect of acidosis, oxidative stress, and glutamate toxicity on the survival of mature and immature cultured cerebellar granule cells

Stel'mashuk, E. V.; Belyaeva, E. A.; Isaev, N. K.

doi:10.1134/s1819712407010084

Cited by 5 publications

(6 citation statements)

References 19 publications

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“…Given that lactic acidosis is a common side effect from lamivudine use, and Stelmashuk, et al had reported that high concentrations of acid is toxic to granular cells of the cerebellum, it is possible that the damaging effect of lamivudine on the cerebellum could be secondary to a concomitant surge in lactic acidosis in the cerebellar environment during lamivudine therapy [17].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the elevated levels of lactic acidosis found in patients under lamivudine treatment may lead to cerebellar degeneration as lactic acidosis have been linked to ataxia and slurred speech which are all coordinated by the cerebellum [15,16]. Moreover, Stelmashuk, et al had reported that high acid concentrations induced death of cerebellar granule cells in culture [17].…”

Section: Introductionmentioning

confidence: 99%

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Histomorphological effect of Lamivudine on the Cerebellum of Wistar rats

Peter¹,

Udoh²,

Ekanem³

2017

Histol Cytol Embryol

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Lamivudine is an anti-retroviral drug used for the treatment of HIV and hepatitis B. It is one of the essential medicines needed in a basic health system. This study was carried out to investigate the detrimental effect of lamivudine on the cerebellum based on the adverse effects of gait disorders manifested by patients using lamivudine. Twenty male Wistar rats divided into two groups of ten rats each were used for the study. Control group A was administered with 1ml of distilled water, while treatment group B was treated with 4.28mg/kg of lamivudine daily for 30 days. On the 30 th day, the rats were euthanized and each cerebellum was harvested immediately. The cerebella were put through routine tissue processing for H/E staining and GFAP immunohistochemical method. The resulting specimens were mounted with DPX and viewed under the light microscope at ×400. Photomicrographs showed shrunken Purkinje cells and distorted granular layer in the cerebellum of group B rats while those of group A rats were healthy. Also, image J counting showed reduced number of cells in the lamivudine group. This correlated with the higher staining intensity for GFAP in the granular layer of group B rats suggesting cellular inflammation and damage. More research is needed to ascertain the molecular mechanism of these distortions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Histomorphological effect of Lamivudine on the Cerebellum of Wistar rats

Peter¹,

Udoh²,

Ekanem³

2017

Histol Cytol Embryol

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“…It is well known that extracellular acidosis induces cell death of cultured cortical, hippocampal, and cerebellar granule neurons (Tombaugh and Sapolsky 1990;Yermolaieva et al 2004;Shen et al 1995;Ding et al 2000;Xiong et al 2004;Stelmashuk et al 2007), and that reduction of [Ca 2? ] i can promote neuronal cell death by activation of apoptosis-inducing cascades (Galli et al 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The underlying mechanisms have been studied intensively both in in vitro and in vivo models of cerebral ischemia (Dirnagl et al 1999;Mergenthaler et al 2004). For example, it has been shown that acidification of the culture medium is sufficient to induce both apoptotic and necrotic cell death of cultured hippocampal, cortical, and cerebellar granule neurons (CGNs) (Tombaugh and Sapolsky 1990;Yermolaieva et al 2004;Shen et al 1995;Ding et al 2000;Xiong et al 2004;Stelmashuk et al 2007). One of the leading causes of neuronal cell death during acidosis seems to be related to the release of the detrimental free radicals as a result of depletion of antioxidative defense (Rehncrona et al 1989;Musleh et al 1994;Ying et al 1999).…”

Section: Introductionmentioning

confidence: 98%

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Acidosis-Induced Zinc-Dependent Death of Cultured Cerebellar Granule Neurons

et al. 2010

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Severe acidosis caused death of cultured cerebellar granule neurons (CGNs). Acidosis was accompanied by a progressive increase of the intracellular zinc ions ([Zn(2+)](i)) and decrease of [Ca(2+)](i). Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), prevented the increase of [Zn(2+)](i) and acidosis-induced neuronal death. However, neuronal death was insensitive to blockade of ASIC1 channels with amiloride, as CGNs display considerably lower expression of ASIC1a than other neurons. The antioxidant trolox and menadione significantly protected neurons from acidotic death. Earlier, we demonstrated that menadione rescues neurons from the deleterious effect of inhibition of mitochondrial complex I (Isaev et al. Neuroreport 15:2227-2231, 2004). We speculate that excessive Zn(2+)-dependent production of reactive oxygen species by mitochondrial complex I may be a general motive for the induction of cell death in CGNs under acidotic conditions.

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