The recombinant C-terminal fragment of tetanus toxin protects against cholinotoxicity by intraseptal injection of β-amyloid peptide (25–35) in rats

Patricio-Martínez, Aleidy; Mendieta, Liliana; Martínez, Isabel; Aguilera, José; Limón, Ilhuicamina Daniel

doi:10.1016/j.neuroscience.2015.11.066

Cited by 14 publications

(22 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies with Hc-TeTx fragment suggest its protection against excitotoxicity and oxidative stress (Herrando-Grabulosa et al, 2013; Radenovic et al, 2014; Patricio-Martínez et al, 2016). In our paradigm, we concentrated on the involvement of inflammatory or oxidative stress in METH-induced toxicity and possible interaction of Hc-TeTx with these mechanisms.…”

Section: Discussionmentioning

confidence: 91%

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

Mendieta

Granado

Aguilera

et al. 2016

IJNPPY

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 91%

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

Mendieta

Granado

Aguilera

et al. 2016

IJNPPY

View full text Add to dashboard Cite

show abstract

“…Agents. donepezil hydrochloride (1511010) was obtained from Affiliated Hospital of Zunyi Medical University (Zunyi, China), Aβ [25][26][27][28][29][30][31][32][33][34][35] (the amino acid sequence is Gly-Ser-Asn-Lys-Gly-A la-Ile-Ile-Gly-Leu-Met) was purchased from Sigma-Aldrich (cat. no.…”

Section: Methodsmentioning

confidence: 99%

“…All experiments were approved by the Ethics committee and performed according to the current guide for the care and use of laboratory animal standard, which was set up by Zunyi Medical University Animal Studies committee (argument number [2015] 2-043). The rats were randomly divided into 7 groups as follows: i) Sham; ii) sham+cZ2HF (400 mg/kg); iii) model (Aβ [25][26][27][28][29][30][31][32][33][34][35] ); iv) Aβ [25][26][27][28][29][30][31][32][33][34][35] +cZ2HF (100 mg/kg); v) Aβ [25][26][27][28][29][30][31][32][33][34][35] +cZ2HF (200 mg/kg); vi) Aβ [25][26][27][28][29][30][31][32][33][34][35] +cZ2HF (400 mg/kg); and vii) Aβ 25-35 +donepezil (1.0 mg/kg) as the positive drug group (n=14 rats per group. Briefly, Aβ [25][26][27]…”

Section: Preparation Of Animal Model and Drug Treatmentmentioning

confidence: 99%

“…Subsequently, Sd rats were anesthetized with an intraperitoneal injection of 2% pentobarbital sodium, the rat's brain was fixed a stereotaxic device, and the following hippocampus needle coordinates were used: 3.5 mm posterior to the bregma, 2.5 mm lateral to the sagittal suture, 3.5 mm beneath the surface of brain. The needle was retained in the bilateral hippocampi for 5 min and the 5 µl Aβ [25][26][27][28][29][30][31][32][33][34][35] was injected. Various doses of cZ2HF were administered orally daily for a continuous period for 15 days.…”

Section: Preparation Of Animal Model and Drug Treatmentmentioning

confidence: 99%

“…However, whether cZ2HF is capable of alleviating learning and memory impairment in Alzheimer's disease (Ad) remains to be elucidated. The present study was designed to explore the effect and mechanism of cZ2HF on β-amyloid [25][26][27][28][29][30][31][32][33][34][35] )-induced impairment in the learning and memory of rats. Morris water maze test was used to determine spatial learning and memory ability in Aβ 25-35 -induced Ad rats and hippocampal neuronal damage and apoptosis were observed using hematoxylin and eosin staining, Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively.…”

mentioning

confidence: 99%

See 2 more Smart Citations

CZ2HF mitigates β-amyloid 25-35 fragment-induced learning and memory impairment through inhibition of neuroinflammation and apoptosis in rats

et al. 2018

View full text Add to dashboard Cite

cu-zhi-2-hao-fang (cZ2HF), a traditional chinese medicine, has been used clinically for the treatment of amnesia. However, whether cZ2HF is capable of alleviating learning and memory impairment in Alzheimer's disease (Ad) remains to be elucidated. The present study was designed to explore the effect and mechanism of cZ2HF on β-amyloid [25][26][27][28][29][30][31][32][33][34][35] )-induced impairment in the learning and memory of rats. Morris water maze test was used to determine spatial learning and memory ability in Aβ 25-35 -induced Ad rats and hippocampal neuronal damage and apoptosis were observed using hematoxylin and eosin staining, Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. The levels of β-amyloid 1-42 (Aβ 1-42 ), pro-inflammatory factors, such as cyclooxygenase-2 (cOX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and apoptosis-associated genes including B cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X, apoptosis regulator (Bax), pro-caspase-3, inhibitor of κB (IκB-α) degradation and phosphorylated-nuclear factor-κB p65 (p-NF-κB p65) activation were analyzed using western blotting. The findings of the present study revealed that CZ2HF treatment significantly attenuated Aβ 25-35 -induced cognitive impairments in rats. Subsequently, cZ2HF treatment markedly inhibited neuronal damage and deletions. Furthermore, cZ2HF reduced TNF-α, IL-1β, cOX-2 protein expression levels, Bax/Bcl-2 ratio, and reduced Aβ 1-42 and active-caspase-3 levels. In addition, IκB-α degradation and p-NF-κB p65 activation were reduced by cZ2HF. These findings suggested that cZ2HF treatment improved Aβ 25-35 -induced learning and memory impairment and hippocampal neuronal injury, and its underlying mechanism may be due to the inhibition of neuroinflammation and neuronal apoptosis. cZ2HF may be a potential agent for the treatment of Ad. Abbreviations:Ad, Alzheimer's disease; cZ2HF, cu-zhi-2-hao-fang; Aβ 25-35 , β-amyloid 25-35; MWM, Morris water maze; H&E, hematoxylin and eosin; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling; cOX-2, cyclooxygenase-2; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; NF-κB p65, nuclear factor-κB p65

show abstract

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

View full text Add to dashboard Cite

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.

show abstract

The recombinant C-terminal fragment of tetanus toxin protects against cholinotoxicity by intraseptal injection of β-amyloid peptide (25–35) in rats

Cited by 14 publications

References 58 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

CZ2HF mitigates β-amyloid 25-35 fragment-induced learning and memory impairment through inhibition of neuroinflammation and apoptosis in rats

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

Contact Info

Product

Resources

About