Abstract:
:Predominant accumulation of ethylmalonic acid (EMA) in tissues and biological fluids is a characteristic of patients affected by short chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy. Neurological abnormalities are frequently found in these disorders, but the mechanisms underlying the brain injury are still obscure. Since hyperlacticacidemia is also found in many affected patients indicating a mitochondrial dysfunction; in the present work, we evaluated the in vitro and ex vivo effects of EMA plus Ca(2+) on mitochondrial integrity and redox balance in succinate-supported brain organelles. We verified that the evaluated parameters were disturbed only when EMA was associated with exogenous micromolar Ca(2+) concentrations. Thus, we found that this short chain organic acid plus Ca(2+) dissipated the membrane potential and provoked mitochondrial swelling, as well as impaired the mitochondrial Ca(2+) retention capacity, resulting in a rapid Ca(2+) release and decreased NAD(P)H matrix content. In contrast, EMA was not able to stimulate mitochondrial hydrogen peroxide generation. We also observed that all these effects were prevented by the mitochondrial Ca(2+) uptake inhibitor ruthenium red and the mitochondrial permeability transition (MPT) inhibitors cyclosporin A (CsA) and ADP. Furthermore, mitochondria isolated from rat brains after in vivo intrastriatal administration of EMA was more susceptible to Ca(2+)-induced swelling, which was fully prevented by CsA and ADP. Finally, EMA significantly decreased striatal slice viability, which was attenuated by CsA. The data strongly indicate that EMA reduced the mitochondrial threshold for Ca(2+)-induced MPT reinforcing the role of this cation in EMA-induced disruption of mitochondrial bioenergetics. It is, therefore, presumed that EMA acting synergistically with Ca(2+) compromises mitochondrial energy homeostasis in the central nervous system that may explain at least in part the neurologic alterations presented by patients with abnormal levels of this organic acid.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Cecatto C,Amaral AU,Leipnitz G,Castilho RF,Wajner Mdoi
10.1007/s12640-014-9460-5subject
Has Abstractpub_date
2014-08-01 00:00:00pages
168-78issue
2eissn
1029-8428issn
1476-3524journal_volume
26pub_type
杂志文章abstract::Neurotransmitters and neuromodulators are essential for normal nervous system development. Disturbances in the expression timetable or intensity of neurotransmitter signalling during critical periods of brain development can lead to permanent damage. Neuroactive drugs and environmental toxins interfere with neurotrans...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033568
更新日期:2007-04-01 00:00:00
abstract::This commentary serves as an introduction to the magnetic resonance imaging (MRI) technique called diffusion kurtosis imaging (DKI) employed in the study by Arab et al. in the present issue of Neurotoxicology Research. In their study, DKI is employed for longitudinal investigation of a methamphetamine intoxication mod...
journal_title:Neurotoxicity research
pub_type: 评论,杂志文章
doi:10.1007/s12640-019-00100-3
更新日期:2020-01-01 00:00:00
abstract::There is a long-standing debate about whether rats have what could be considered a prefrontal cortex (PFC) and, if they do, what its primate homologue is. Anatomical evidence supports the view that the rat medial PFC is related to both the primate anterior cingulate cortex (ACC) and the dorsolateral PFC. Functionally ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033814
更新日期:2008-10-01 00:00:00
abstract::Chronic alcohol consumption may cause neurodevelopmental and neurodegenerative disorders. Alcohol neurotoxicity is associated with the production of acetaldehyde and reactive oxygen species that induce oxidative DNA damage. However, the molecular mechanisms by which ethanol disturbs the DNA damage response (DDR), resu...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9554-8
更新日期:2016-01-01 00:00:00
abstract::Parkinson's disease is a slowly progressing disease, due to a lesion of dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in the striatum. It is now accepted that several environmental agents including the herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now nothing ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-010-9153-7
更新日期:2011-01-01 00:00:00
abstract::Accumulating data support axonal degeneration as the major determinant of irreversible neurological disability in patients with multiple sclerosis (MS). The extent of axonal injury correlates with the degree of inflammation in active MS lesions and occurs at early stages of disease, indicating that inflammatory demyel...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033380
更新日期:2003-01-01 00:00:00
abstract::The author group has previously established an in vivo subchronic cigarette smoke (CS) exposure rat model, in which the systemic oxidative burden as well as the modulation of local anti-oxidative enzymes in the lung has been demonstrated. Oxidative stress has been shown to induce pro-inflammatory cytokine release, inc...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-011-9301-8
更新日期:2012-08-01 00:00:00
abstract::Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analy...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9483-y
更新日期:2015-01-01 00:00:00
abstract::Botulinum neurotoxin (BoNT) has been used clinically since 1980, with an ever-increasing range of clinical applications. This has coincided with a period of massively expanded interest in the underlying biology of the neurotoxin. Tremendous advances have taken place in the scientific understanding of neurotoxin struct...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033931
更新日期:2006-04-01 00:00:00
abstract::Small-molecule inhibitors of neurofibrillary lesion formation may have utility for treatment of Alzheimer's disease and certain forms of frontotemporal lobar degeneration. These lesions are composed largely of tau protein, which aggregates to form intracellular fibrils in affected neurons. Previously it was shown that...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9028-y
更新日期:2009-04-01 00:00:00
abstract::Hyperphosphorylated tau is an important pathological agent in Alzheimer's disease (AD). Tau effluxes from the brain to the blood could potentially stimulate the production of naturally occurring antibodies (NAbs). We aimed to investigate whether NAbs to tau (NAbs-tau) was generated in human blood and to figure out the...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00161-9
更新日期:2020-04-01 00:00:00
abstract::Impulse control disorders (ICDs) comprise a wide spectrum of abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian treatment. Some ICDs share several essential features with substance use disorders. In this work, we have studied the addiction-related gene ankyrin repe...
journal_title:Neurotoxicity research
pub_type: 杂志文章,多中心研究
doi:10.1007/s12640-014-9504-x
更新日期:2015-04-01 00:00:00
abstract::The sigma1 receptor (σ1R) is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it modulates Ca2+ exchange between the ER and mitochondria by interacting with inositol-1,4,5 trisphosphate receptors (IP3Rs). The σ1R is highly expressed in the central nervous syste...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9838-2
更新日期:2019-01-01 00:00:00
abstract::Microglial activation and subsequent release of toxic pro-inflammatory factors are believed to play an important role in neuronal cell death associated with Parkinson's disease (PD). Compounds that inhibit microglia activation and suppress pro-inflammatory factor release have been reported to have neuroprotective effe...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9328-5
更新日期:2013-02-01 00:00:00
abstract::Mercury is a toxic metal shown to have harmful effects on human health. Several studies have reported high blood mercury concentrations as a risk factor for autism spectrum disorders (ASDs), while other studies have reported no such association. The goal of this study was to investigate the association between blood m...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9321-z
更新日期:2013-01-01 00:00:00
abstract::Neural transplantation is a promising treatment strategy that can restore the motor, sensory and cognitive functions in the rat middle cerebral artery occlusion (MCAO) model of stroke. In particular, neuronal cells derived from a human teratocarcinoma cell line, called hNT neurons or LBS neurons (clinical grade prepar...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/10298420290015908
更新日期:2002-03-01 00:00:00
abstract::Cognitive impairment in depression may be one of the more practically important aspects of the illness, responsible for much of its morbidity. It also is at the heart of its psychopathology, may contribute to strategies of treatment, and may give us a more easily quantifiable measure of impaired function to correlate ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033237
更新日期:2006-10-01 00:00:00
abstract::Sepsis-associated encephalopathy causes brain dysfunction that can result in cognitive impairments in sepsis survivor patients. In previous work, we showed that simvastatin attenuated oxidative stress in brain structures related to memory in septic rats. However, there is still a need to evaluate the long-term impact ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00222-z
更新日期:2020-12-01 00:00:00
abstract::Pterostilbene (PTE), a natural analog of resveratrol, is available both as a diet ingredient and a dietary supplement. The present study was undertaken to assess the effect of PTE on the activity of antiepileptic drugs in the acute seizure tests in mice, i.e., the intravenous pentetrazole (iv PTZ) seizure threshold, m...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00021-1
更新日期:2019-11-01 00:00:00
abstract::Cellular oxidative stress and energy failure were shown to be involved in Glutamate (L-Glu) neurotoxicity, whereas, acetyl-L-carnitine (ALCAR) and ±DL-α-lipoic acid (LA) are known to be key players in the mitochondrial energy production. To evaluate the effects of the above antioxidants, adult rats were pretreated wit...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-010-9165-3
更新日期:2011-02-01 00:00:00
abstract::The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 microl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when th...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033183
更新日期:2004-01-01 00:00:00
abstract::The purpose of this study was to determine whether exposure to an extremely low-frequency magnetic field (ELF-MF, 50 Hz) affects the outcome of postischemic damage in the hippocampus of Mongolian gerbils. After 10-min bilateral carotid occlusion, the gerbils were continuously exposed to ELF-MF (average magnetic induct...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9333-8
更新日期:2013-01-01 00:00:00
abstract::There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson's disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9468-x
更新日期:2014-10-01 00:00:00
abstract::A widely held view suggests that homocysteine (Hcy) can contribute to neurodegeneration through promotion of oxidative stress. There is evidence that homocysteine is toxic to cerebellar Purkinje neurons in vitro; however, in vivo action of Hcy on Purkinje cell has not been investigated so far. Thus, this study was des...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9979-y
更新日期:2019-04-01 00:00:00
abstract::Hypoxia-inducible factor-1 (HIF-1) plays an important role in neural progenitor cell (NPC) propagation and dopaminergic differentiation. In the presence of oxygen and iron, hypoxia-inducible factor 1 alpha (HIF-1alpha) is rapidly degraded via the prolyl hydroxylase (PHD)/VHL pathway. In addition to hypoxia, various no...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9043-z
更新日期:2009-05-01 00:00:00
abstract::The isolated sciatic nerve of the frog was used to assess the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the peripheral nervous system. For each experiment, both sciatic nerves were used. The evoked compound action potentials of the nerves were monitored for over 48 h as an indication of their ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/10298420290007592
更新日期:2002-02-01 00:00:00
abstract::Dopamine can be autoxidized to superoxides and quinones. Superoxides can form hydroxyl radicals that are highly reactive with lipids, proteins and DNA leading to neuronal damage and cell death. We used a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system to evaluate the effects of dopa...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033288
更新日期:2000-02-01 00:00:00
abstract::Calcitriol (1,25-dihydroxyvitamin D3), an active metabolite of vitamin D3, besides the role in calcium and phosphorus metabolism, plays a role in maintaining the functions of the brain. Active forms of vitamin D3 stimulate neurotrophic factors' expression, regulate brain immune processes, and prevent neuronal damage. ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9652-2
更新日期:2016-11-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from the progressive loss of motor neurons in the spinal cord and brain. To date, clinically effective neuroprotective agents have not been available. The current study demonstrates for the first time that huperzine A, a potential neuroprotec...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033367
更新日期:2008-01-01 00:00:00
abstract::To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effec...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033559
更新日期:2008-04-01 00:00:00