The C-terminal domain of the heavy chain of tetanus toxin given by intramuscular injection causes neuroprotection and improves the motor behavior in rats treated with 6-hydroxydopamine

Mendieta, Liliana; Bautista, Elizabeth; Sánchez, Alejandra Consuelo; Guevara, Jorge; Herrando-Grabulosa, Mireia; Morán, J.L.; Martínez, Rebeca; Aguilera, José; Limón, Ilhuicamina Daniel

doi:10.1016/j.neures.2012.08.006

Cited by 18 publications

(15 citation statements)

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“…However, overactivation of inflammatory mechanism can be a source of damage by itself (Hurley and Tizabi, 2013; Tizabi et al, 2014; Moratalla et al, 2015). Hence, the significant decrease in astrogliosis on day 7 post METH treatments might be indicative of a delayed antiinflammatory effect of Hc-TeTx similar to what was seen previously against 6-OHDA (Mendieta et al, 2012). However, further studies on possible antiinflammatory effects of Hc-TeTx and interaction between oxidative stress and immune/inflammatory system need to be carried out.…”

Section: Discussionsupporting

confidence: 72%

“…These studies show that Hc-TeTx is able to decrease dopaminergic lesions induced by MPP + and 6-OHDA (Mendieta et al, 2009, 2012). In this study, we provide the first evidence that Hc-TeTx fragment can also protect striatal terminal loss and motor impairments induced by acute METH administration.…”

Section: Discussionmentioning

confidence: 94%

“…The animals were administered Hc-TeTx fragment (40 μg/kg) in the gastrocnemius muscle for 3 consecutive days, with the first 1 hour following the last METH injection and the other 2 at 24 and 48 hours after last METH injection as described previously (Mendieta et al, 2012). Controls received the vehicle (SSI, saline solution).…”

Section: Methodsmentioning

confidence: 99%

“…The efficacy of the recombinant Hc-TeTx fragment in vivo was later confirmed by using the Hc-TeTx against dopaminergic lesion induced by MPP + (Mendieta et al, 2009) or 6-hydroxydopamine (6-OHDA) in rats (Mendieta et al, 2012; Sánchez-González et al, 2014). Hc-TeTx has also been used as a neurotrophic agent to prevent damage in neurodegenerative models such as amyotrophic lateral sclerosis and ischemia (Moreno-Igoa et al, 2010; Toivonen et al, 2010; Calvo et al, 2011; Radenovic et al, 2014).…”

Section: Introductionmentioning

confidence: 96%

“…Based on previous animal studies (Mendieta et al, 2012; Sánchez-González et al, 2014), we administered i.m. the recombinant fragment of Hc-TeTx for 3 consecutive days after acute METH treatment in mice and examined DA degeneration by evaluating TH and DAT fiber loss in the striatum and stereological neuronal count in the substantia nigra.…”

Section: Introductionmentioning

confidence: 99%

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Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice

Mendieta

Granado

Aguilera

et al. 2016

IJNPPY

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Background:The C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) is a nontoxic peptide with demonstrated in vitro and in vivo neuroprotective effects against striatal dopaminergic damage induced by 1-methyl-4-phenylpyridinium and 6-hydoxydopamine, suggesting its possible therapeutic potential in Parkinson’s disease. Methamphetamine, a widely abused psychostimulant, has selective dopaminergic neurotoxicity in rodents, monkeys, and humans. This study was undertaken to determine whether Hc-TeTx might also protect against methamphetamine-induced dopaminergic neurotoxicity and the consequent motor impairment.Methods:For this purpose, we treated mice with a toxic regimen of methamphetamine (4mg/kg, 3 consecutive i.p. injections, 3 hours apart) followed by 3 injections of 40 ug/kg of Hc-TeTx into grastrocnemius muscle at 1, 24, and 48 hours post methamphetamine treatment.Results:We found that Hc-TeTx significantly reduced the loss of dopaminergic markers tyrosine hydroxylase and dopamine transporter and the increases in silver staining (a well stablished degeneration marker) induced by methamphetamine in the striatum. Moreover, Hc-TeTx prevented the increase of neuronal nitric oxide synthase but did not affect microglia activation induced by methamphetamine. Stereological neuronal count in the substantia nigra indicated loss of tyrosine hydroxylase-positive neurons after methamphetamine that was partially prevented by Hc-TeTx. Importantly, impairment in motor behaviors post methamphetamine treatment were significantly reduced by Hc-TeTx.Conclusions:Here we demonstrate that Hc-TeTx can provide significant protection against acute methamphetamine-induced neurotoxicity and motor impairment, suggesting its therapeutic potential in methamphetamine abusers.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice

Mendieta

Granado

Aguilera

et al. 2016

IJNPPY

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The C‐terminal fragment of the heavy chain of the tetanus toxin (Hc‐TeTx) improves motor activity and neuronal morphology in the limbic system of aged mice

Vázquez-Roque

Pacheco-Flores²,

Penagos-Corzo³

et al. 2020

Synapse

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In the aging process, the brain presents biochemical and morphological alterations.The neurons of the limbic system show reduced size dendrites, in addition to the loss of dendritic spines. These disturbances trigger a decrease in motor and cognitive function. Likewise, it is reported that during aging, in the brain, there is a significant decrease in neurotrophic factors, which are essential in promoting the survival and plasticity of neurons. The carboxyl-terminal fragment of the heavy chain of the tetanus toxin (Hc-TeTx) acts similarly to neurotrophic factors, inducing neuroprotection in different models of neuronal damage. The aim here, was to evaluate the effect of Hc-TeTx on the motor processes of elderly mice (18 months old), and its impact on the dendritic morphology and density of dendritic spines of neurons in the limbic system. The morphological analysis in the dendrites was evaluated employing Golgi-Cox staining. Hc-TeTx was administered (0.5 mg/kg) intraperitoneally for three days in 18-month-old mice. Locomotor activity was evaluated in a novel environment 30 days after the last administration of Hc-TeTx. Mice treated with Hc-TeTx showed significant changes in their motor behavior, and an increased dendritic spine density of pyramidal neurons in layers 3 and 5 of the prefrontal cortex in the hippocampus, and medium spiny neurons of the nucleus accumbens (NAcc). In conclusion, the Hc-TeTx improves the plasticity of the brain regions of the limbic system of aged mice. Therefore, it is proposed as a pharmacological alternative to prevent or delay brain damage during aging.

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6-OHDA-Induced Changes in Parkinson`s Disease-Related Gene Expression are not Affected by the Overexpression of PGAM5 in In Vitro Differentiated Embryonic Mesencephalic Cells

et al. 2015

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LUHMES cells, a recently established line of immortalized embryonic mesencephalic cells, are the novel in vitro model for studying Parkinson’s disease (PD) and dopaminergic neuron biology. Phosphoglyceromutase 5 (PGAM5) is a mitochondrial protein involved in mitophagy, mitochondria dynamics, and other processes important for PD pathogenesis. We tested the impact of lentiviral overexpression of PGAM5 protein in LUHMES cells on their differentiation and expression of 84 PD-related genes. LUHMES cells were transduced with PGAM5 or mock and treated with 100 μM 6-hydroxydopamine (6-OHDA), a model PD neurotoxin. Real-Time PCR analysis revealed that the treatment with 6-OHDA-induced changes in expression of 44 PD-related genes. PGAM5 transduction alone did not cause alternations in PD-related genes expression, nor it affected changes in gene expression mediated by 6-OHDA. The 6-OHDA-induced PD-related gene expression profile of LUHMES cells is presented for the first time and widely discussed.Electronic supplementary materialThe online version of this article (doi:10.1007/s10571-015-0207-5) contains supplementary material, which is available to authorized users.

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The C-terminal domain of the heavy chain of tetanus toxin given by intramuscular injection causes neuroprotection and improves the motor behavior in rats treated with 6-hydroxydopamine

Cited by 18 publications

References 44 publications

Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice

Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice

The C‐terminal fragment of the heavy chain of the tetanus toxin (Hc‐TeTx) improves motor activity and neuronal morphology in the limbic system of aged mice

6-OHDA-Induced Changes in Parkinson`s Disease-Related Gene Expression are not Affected by the Overexpression of PGAM5 in In Vitro Differentiated Embryonic Mesencephalic Cells

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