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Neurotoxicity Research

Debapriya Garabadu, Mahima Sharma
Eugenol is one of the essential chemical constituents of several functional food plants including Eugenia caryophyllata Thunb. (Family: Myrtaceae). Eugenol exhibits neuroprotective and anti-stress activities through multimodal mechanisms of action. Further, eugenol exerts anti-amnesic activity in Alzheimer's disease (AD)-like animals perhaps through anti-oxidant mechanism to date. Hence, the present study was designed to elaborate the anti-amnesic activity of eugenol in scopolamine-challenged rodents. Scopolamine (3 mg/kg/day, i...
February 9, 2019: Neurotoxicity Research
Alka Kaushal, Willayat Yousuf Wani, Amanjit Bal, Kiran Dip Gill, Jyotdeep Kaur
Alzheimer's disease (AD) is the most common cause of progressive decline of memory function in aged humans. To study about a disease mechanism and progression, animal models for the specific disease are needed. For AD, although highly valid animal models exist, none of the existing models recapitulates all aspects of human AD. The pathogenic mechanisms involved in AD are diverse and thus it is difficult to recapitulate human AD in model organisms. Intracerebroventricular (ICV) injection of okadaic acid (OKA), a protein phosphatase 2A (PP2A) inhibitor, in rats causes neurotoxicity associated with neurofibrillary degeneration...
February 7, 2019: Neurotoxicity Research
Higor Alves Iha, Naofumi Kunisawa, Saki Shimizu, Misaki Onishi, Yuji Nomura, Nami Matsubara, Chihiro Iwai, Mizuki Ogawa, Mai Hashimura, Kazuaki Sato, Masaki Kato, Yukihiro Ohno
Organophosphates (OPs) inhibit cholinesterase and hyperactivate the acetylcholinergic nervous system in the brain, causing motor disorders (e.g., tremor and seizures). Here, we performed behavioral and immunohistochemical studies in mice and rats to investigate the tremorgenic mechanism of paraoxon, an active metabolite of parathion. Treating animals with paraoxon (0.15-0.6 mg/kg, i.p.) elicited kinetic tremor in a dose-dependent manner. Expressional analysis of Fos protein, a biomarker of neural excitation, revealed that a tremorgenic dose of paraoxon (0...
February 7, 2019: Neurotoxicity Research
Sachchida Nand Rai, Hagera Dilnashin, Hareram Birla, Saumitra Sen Singh, Walia Zahra, Aaina Singh Rathore, Brijesh Kumar Singh, Surya Pratap Singh
Disruption of Akt and Erk-mediated signal transduction significantly contributes in the pathogenesis of various neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's diseases, Huntington's disease, and many others. These regulatory proteins serve as the regulator of cell survival, motility, transcription, metabolism, and progression of the cell cycle. Therefore, targeting Akt and Erk pathway has been proposed as a reasonable approach to suppress ND progression. This review has emphasized on involvement of Akt/Erk cascade in the neurodegeneration...
February 1, 2019: Neurotoxicity Research
Ghada A Badawi, Mai A Abd El Fattah, Hala F Zaki, Moushira I El Sayed
L-dopa is still considered as the gold standard therapy for Parkinson's disease (PD); however, L-dopa-induced dyskinesia (LID) is a serious complication of long-term L-dopa treatment. The present study investigated the therapeutic potential of sitagliptin and liraglutide in comparisons with L-dopa against PD. In addition, their capacity to modulate L-dopa dose and/or side effects was investigated, too. Rats were injected with rotenone (3 mg/kg/day, s.c.) for 10 consecutive days to induce the experimental PD...
January 23, 2019: Neurotoxicity Research
Mashoque Ahmad Rather, Arokiasamy Justin-Thenmozhi, Thamilarasan Manivasagam, Chidambaram Saravanababu, Gilles J Guillemin, Musthafa Mohamed Essa
Asiatic acid (AA), a triterpenoid present in Centella asiatica, possesses the ability to cross blood brain barrier and received considerable attention for its neuroprotective role. We have reported the benefit of AA against aluminum chloride (AlCl3 )-induced amyloid pathology, enhanced acetylcholine esterase (AChE) activity, and inflammation in Alzheimer's disease (AD) like model rats. Based on that, to find the exact mechanism of action of AA, the present study was designed to evaluate the oxidative stress, tau pathology, apoptosis, and Akt/GSK3β signaling pathway on AlCl3 -induced neurotoxicity in Wistar rats...
January 22, 2019: Neurotoxicity Research
Laura Scott, Timothy Downing
The link between neonatal BMAA exposure and neurodegeneration has recently been demonstrated in rodents. We therefore investigated the behavioral and histopathological dose response to BMAA administered as a single dose. We report here that exposure to a BMAA dose as low as 50 mg/kg on PND 3 caused mild short-term behavioral alterations as well as beta-amyloid deposition together with neuronal loss in the hippocampus of adult rats. Additionally, all histopathological abnormalities and behavioral deficits that had been observed in a previous study in the brain and spinal cord tissue of rats exposed to 400 mg/kg BMAA on PND 3 were also observed here in the brain and spinal cord tissue of male and female rats exposed to 100 mg/kg BMAA at the same age, although the proteinopathy burdens and volume losses were lower...
January 21, 2019: Neurotoxicity Research
Gloria Castellano-Gonzalez, Kelly R Jacobs, Emily Don, Nicholas J Cole, Seray Adams, Chai K Lim, David B Lovejoy, Gilles J Guillemin
Upregulation of the kynurenine pathway (KP) of tryptophan metabolism is commonly observed in neurodegenerative disease. When activated, L-kynurenine (KYN) increases in the periphery and central nervous system where it is further metabolised to other neuroactive metabolites including 3-hydroxykynurenine (3-HK), kynurenic acid (KYNA) and quinolinic acid (QUIN). Particularly biologically relevant metabolites are 3-HK and QUIN, formed downstream of the enzyme kynurenine 3-monooxygenase (KMO) which plays a pivotal role in maintaining KP homeostasis...
January 21, 2019: Neurotoxicity Research
Ting Zhang, Shan Wang, Qiao Niu
To investigate the effect of aluminum-maltolate [Al(mal)3] on the expression of ApoER2, VLDLRs, and LRP1 in PC12-ApoE4 cells. The lentiviral vector carrying human ApoE4 gene was transfected into PC12 cells; after screening with puromycin, PC12 cells carrying ApoE4 gene (PC12-ApoE4 cells) were established. After 24-h treatment with Al(mal)3, the cell survival rate was measured by CCK-8 assay. The expression of Aβ40 and Aβ42 was detected by ELISA assay; the expression of the APP, ApoER2, LRP1, and VLDLRs genes was detected by RT-PCR, and Western blot assay was used to detect the expression of the APP, ApoER2, LRP1, and VLDLRs proteins...
January 16, 2019: Neurotoxicity Research
Victoria Palafox-Sanchez, Victoria Sosti, Gabriel Ramirez-García, Jaime Kulisevsky, José Aguilera, I Daniel Limón
Levodopa-induced dyskinesia (LID) is the main side effect associated with levodopa treatment and represents the biggest challenge for Parkinson's disease therapy. While the overexpression of ΔFosB transcription factor is related to the development of LID, few studies have been undertaken on fosB gene transcriptional regulation induced by levodopa in vivo. The aim of this study is to evaluate the expression of ΔFosB mRNA and FosB mRNA in the striatum after acute, chronic, and subchronic levodopa treatment in rats with unilateral 6-OHDA-lesion in the medial forebrain bundle...
January 15, 2019: Neurotoxicity Research
Musthafa Mohamed Essa, Marzieh Moghadas, Taher Ba-Omar, M Walid Qoronfleh, Gilles J Guillemin, Thamilarasan Manivasagam, Arokiasamy Justin-Thenmozhi, Bipul Ray, Abid Bhat, Saravana Babu Chidambaram, Amanda J Fernandes, Byoung-Joon Song, Mohammed Akbar
Huntington's disease (HD) is a hereditary neurodegenerative disease of the central nervous system (CNS). Onset of HD occurs between the ages of 30 and 50 years, although few cases are reported among children and elderly. HD appears to be less common in some populations such as those of Japanese, Chinese, and African descent. Clinical features of HD include motor dysfunction (involuntary movements of the face and body, abnormalities in gait, posture and balance), cognitive impairment (obsessive-compulsive disorder), and psychiatric disorders (dementia)...
January 11, 2019: Neurotoxicity Research
Hongxia Zhang, Kun Wang
In this work, we evaluated the functional role of microRNA-33-5p (miR-33-5p) in regulating bupivacaine (Bv)-induced neural apoptosis in dorsal root ganglion (DRG) cells. DRG was extracted from adult mice and treated with BV in vitro. A TUNEL assay was applied to assess neural apoptosis among DRG cells. A qRT-PCR assay was applied to assess miR-33-5p expression among BV-treated DRG cells. MiR-33-5p was genetically knocked down in DRG cells. Its effect on BV-induced neural apoptosis was further evaluated by TUNEL assay...
January 8, 2019: Neurotoxicity Research
Rebecca A Bailey, Arnold Gutierrez, Tara L Kyser, Ann M Hemmerle, Jillian R Hufgard, Kim B Seroogy, Charles V Vorhees, Michael T Williams
Manganese (Mn) is an essential nutrient especially during development, but Mn overexposure (MnOE) produces long-term cognitive deficits. Evidence of long-term changes in dopamine in the neostriatum was found in rats from developmental MnOE previously. To examine the relationship between MnOE and dopamine, we tested whether the effects of developmental MnOE would be exaggerated by dopamine reductions induced by 6-hydroxydopamine (6-OHDA) neostriatal infusion when the rats were adults. The experiment consisted of four groups of females and males: Vehicle/Sham, MnOE/Sham, Vehicle/6-OHDA, and MnOE/6-OHDA...
January 5, 2019: Neurotoxicity Research
Akanksha Mishra, Sairam Krishnamurthy
Parkinson's disease (PD) is one of the widely reported neurodegenerative disorders affecting more than ten million people worldwide. Due to therapeutic limitations and several adverse effects associated with currently used drugs, it is crucial to search for safe and effective options for treatment of PD. Oxidative stress, mitochondrial dysfunction, α-synuclein oligomeric aggregates, and glucocerebrosidase (GCase) deficiency are involved in PD pathogenesis. Rebamipide, an anti-ulcer drug, is a proven free-radical scavenger and antioxidant...
January 4, 2019: Neurotoxicity Research
Felipe Patricio, Irving Parra, Isabel Martínez, Francisca Pérez-Severiano, Sergio Montes, José Aguilera, Ilhuicamina Daniel Limón, Yousef Tizabi, Liliana Mendieta
Reports indicate that striatal dopaminergic damage induced by 6-hydoxydopamine (6-OHDA) can be blocked by C-terminal domain of tetanus toxin (Hc-TeTx), suggesting possible therapeutic potential of Hc-TeTx in Parkinson's disease (PD). Pramipexole (PPX), a D2/D3 dopaminergic agonist, is currently used in PD treatment. The purpose of this study was to gain some understanding of the actions of each drug, including potential antioxidant and anti-inflammatory effects and importantly, to determine whether the combination of the two drugs would be superior to each alone...
January 3, 2019: Neurotoxicity Research
Fernanda Crunfli, Talita A Vrechi, Andressa P Costa, Andréa S Torrão
The cannabinoid system has the ability to modulate cellular and molecular mechanisms, including excitotoxicity, oxidative stress, apoptosis, and inflammation, acting as a neuroprotective agent, by its relationship with signaling pathways associated to the control of cell proliferation, differentiation, and survival. Recent reports have raised new perspectives on the possible role of cannabinoid system in neurodegenerative diseases like Alzheimer disease's (AD). AD is a neurodegenerative disorder characterized by the presence of amyloid plaques, neurofibrillary tangles, neuronal death, and progressive cognitive loss, which could be caused by energy metabolism impairment, changes in insulin signaling, chronic oxidative stress, neuroinflammation, Tau hyperphosphorylation, and Aβ deposition in the brain...
January 3, 2019: Neurotoxicity Research
Krishnapriya Madhu Varier, Thangarajan Sumathi
Parkinson's disease (PD) remarks its pathology by affecting the patient's movements and postural instability by dopaminergic loss in the substantia nigra of midbrain. The disease is characterized by the accumulation of alpha-synuclein protein followed by dementia symptoms. Moreover, the pathology enhances the production of monoamine oxidases A and B (MAO A and B), leucine-rich repeat kinase 2 (LRRK2), phosphate and tensin homolog (PTEN), PTEN-induced putative kinase 1 (PINK1), and PARK7 (deglycase 1 (DJ-1))...
December 19, 2018: Neurotoxicity Research
Michael Maes, Buranee Kanchanatawan, Sunee Sirivichayakul, André F Carvalho
Increased gut permeability (leaky gut) with increased translocation of Gram-negative bacteria plays a role in the gut-brain axis through effects on systemic immune-inflammatory processes. Deficit schizophrenia is characterized by an immune-inflammatory response combined with a deficit in natural IgM antibodies to oxidative-specific epitopes (OSEs), which are a first-line defense against bacterial infections. This study measured plasma IgA/IgM responses to 5 Gram-negative bacteria in association with IgM responses to malondialdehyde (MDA) and azelaic acid in 80 schizophrenia patients (40 with the deficit syndrome and 40 without) and in 38 healthy controls...
December 15, 2018: Neurotoxicity Research
Hye-Ju Han, Sokho Kim, Jungkee Kwon
Prion protein peptide (PrP) has been associated with neurotoxicity in brain cells and progression of prion diseases due to spongiform degeneration and accumulation of the infectious scrapie prion protein (PrPSc ). Autophagy has been shown to provide protective functions for neurodegenerative diseases, including prion disease. Thymosin beta 4 (Tβ4 ) plays a key role in the nervous system, providing a neuronal growth effect that includes motility, neurite outgrowth, and proliferation. However, the effect of Tβ4 on autophagy in prion disease has not been investigated...
December 15, 2018: Neurotoxicity Research
Peter W French, Russell Ludowyke, Gilles J Guillemin
We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic lateral sclerosis (ALS). ALS is the most common form of motor neuron disease (MND) in adults. It is a progressive and fatal disease. Approximately 90% cases of ALS are sporadic, and 5-10% are due to genetic mutations (familial). About 25 genes implicated in familial ALS have been identified so far, including SOD1 and TARDBP, the gene encoding 43 kDa transactive response (TAR) DNA-binding protein (TDP-43). Despite intensive research over many decades, the aetiology of sporadic ALS is still unknown...
December 5, 2018: Neurotoxicity Research
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