RETRACTED: Acetylcholinesterase inhibitors enhance cognitive functions in rats following hypobaric hypoxia

Muthuraju, Sangu; Maiti, Panchanan; Solanki, Preeti; Sharma, Alpesh K.; Amitabh,; Singh, Shashi Bala; Prasad, Dipti; Ilavazhagan, G.

doi:10.1016/j.bbr.2009.03.026

Cited by 68 publications

(32 citation statements)

References 55 publications

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“…On the other hand, our results of the AChE inhibitor oxygen-dependent impact on AChE activity (fig. 2) are confirmed by others [30]. …”

Section: Discussionsupporting

confidence: 79%

“…In line with our findings, there are several studies that suggest an increased antioxidant capacity of AChE inhibitors in the rodent brain [49,50]. Interestingly, in the presented model of oxygen toxicity in the developing brain and adult rats following hypobaric hypoxia [30], there was no inhibition of AChE activity under normoxic conditions. A possible explanation could be the effect of microRNAs as regulators of cholinergic anti-inflammatory pathways by targeting neuronal AChE activity [51,52].…”

Section: Discussionsupporting

confidence: 78%

“…1). Neurodegeneration is often linked with an increasing expression or activity of AChE as demonstrated in the brain of focal cerebral ischemic rats [29] and rats following hypobaric hypoxia [30]. Additionally, various neuronal cell culture studies suggested a correlation of increased AChE expression levels and an induction of apoptotic cell death [1,2,8,31].…”

Section: Discussionmentioning

confidence: 99%

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Oxygen Toxicity Is Reduced by Acetylcholinesterase Inhibition in the Developing Rat Brain

et al. 2013

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The cholinergic anti-inflammatory pathway is a neural mechanism that suppresses the innate inflammatory response and controls inflammation employing acetylcholine as the key endogenous mediator. In this study, we investigated the effects of the cholinergic agonists, physostigmine and donepezil, on neurodegeneration, inflammation and oxidative stress during oxygen toxicity in the developing rat brain. The aim of this study was to investigate the level of neurodegeneration, expression of proinflammatory cytokines, glutathione and lipid peroxidation after hyperoxia and treatment with the acetylcholinesterase (AChE) inhibitors, physostigmine and donepezil in the brain of neonatal rats. Six-day-old Wistar rats were exposed to 80% oxygen for 12-24 h and received 100 μg/kg physostigmine or 200 μg/kg donepezil intraperitoneally. Sex-matched littermates kept in room air and injected with normal saline, physostigmine or donepezil served as controls. Treatment with both inhibitors significantly reduced hyperoxia-triggered activity of AChE, neural cell death and the upregulation of the proinflammatory cytokines IL-1β and TNF-α in the immature rat brain on the mRNA and protein level. In parallel, hyperoxia-induced oxidative stress was reduced by concomitant physostigmine and donepezil administration, as shown by an increased reduced/oxidized glutathione ratio and attenuated malondialdehyde levels, as a sign of lipid peroxidation. Our results suggest that a single treatment with AChE inhibitors at the beginning of hyperoxia attenuated the detrimental effects of oxygen toxicity in the developing brain and may pave the way for AChE inhibitors, which are currently used for the treatment of Alzheimer's disease, as potential candidates for adjunctive neuroprotective therapies to the immature brain.

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“…On the other hand, our results of the AChE inhibitor oxygen-dependent impact on AChE activity (fig. 2) are confirmed by others [30]. …”

Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

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Oxygen Toxicity Is Reduced by Acetylcholinesterase Inhibition in the Developing Rat Brain

et al. 2013

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“…Calcium mediated free radical generation through activation of PhospholipaseA2 (PLA2), Xanthine Oxidase and Monoamine Oxidase by Calcium Calmodulin complex has also been reported in the hippocampus following hypoxic insult (Barhwal et al 2009a). Exposure to hypobaric hypoxia also results in alterations in cholinergic transmission and altered corticosterone that could contribute to the memory impairment (Hota et al 2009;Muthuraju et al 2009). …”

Section: Neuronal Response To Hypoxiamentioning

confidence: 99%

Neurodegeneration in Hypoxia: Implications in Aging

Hota

Singh

2012

Brain Aging and Therapeutic Interventions

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Hypoxia and ischemia resulting in reduced oxygen delivery to brain tissues is reported to cause neurodegeneration in both in vitro and in vivo models. Similar decrease in partial pressure of oxygen occurs on ascent to high altitude, a situation referred to as hypobaric hypoxia that limits oxygen availability to the brain. Our studies on human subjects reveal decrease in vigilance and response time along with decreased cerebral oxygenation which is both altitude and duration dependent. Alterations in evoked potentials and change in hedonic matrix were also observed following exposure to high altitude environment. Investigations in animal models exposed to simulated altitude showed occurrence of oxidative stress, neurodegeneration and memory impairment. This hypoxic response of neurons is multi-factorial and involves complex signaling pathways thereby limiting the therapeutic efficacy of several antioxidants in ameliorating hypobaric hypoxia-induced memory impairment. Animals exposed to hypobaric hypoxia show depletion in the antioxidant status along with increased free radical generation. Neuromorphological studies revealed neurodegeneration and dendritic atrophy in the hippocampus. Altered neurotransmitter synthesis, release and metabolism have also been observed along with occurrence of calcium overload in hypoxic neuronal cells. These changes in the hypoxic brain find an analogy with the aging related changes that include decreased conduction rate, generation of free radicals, protein oxidation and cellular apoptosis. Administration of N-acetyl cysteine to animals exposed to hypobaric hypoxia showed considerable improvement in memory functions along with decrease in free radical generation. Acetyl-L-Carnitine administration during hypobaric hypoxia also improved the cognitive capabilities in animal models. Our investigations revealed a multifactorial action of Acetyl-L-Carnitine that included

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“…In the experimental scenario, numerous studies with mammalian investigate the effects of irreversible inhibitors of acetylcholinesterase, AChE, the enzyme responsible for the catalysis of ACh present in the synaptic space, measuring ACh and AChE brain levels and the performance animals models in spatial recognition tests (Bennett et al, 2007;Muthuraju et al, 2009). These studies pointed to learning improvement due to the activation of the cholinergic system.…”

Section: Cholinergic Hypothesismentioning

confidence: 99%

Activity Evaluation and Toxicological Profile of New Potential Metal Protein Attenuating Compounds in Biological Models of Alzheimer S Disease

Falco¹

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RETRACTED: Acetylcholinesterase inhibitors enhance cognitive functions in rats following hypobaric hypoxia

Cited by 68 publications

References 55 publications

Oxygen Toxicity Is Reduced by Acetylcholinesterase Inhibition in the Developing Rat Brain

Oxygen Toxicity Is Reduced by Acetylcholinesterase Inhibition in the Developing Rat Brain

Neurodegeneration in Hypoxia: Implications in Aging

Activity Evaluation and Toxicological Profile of New Potential Metal Protein Attenuating Compounds in Biological Models of Alzheimer S Disease

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