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Galectins are animal lectins that bind to β-galactosides, such as lactose and N-acetyllactosamine, contained in glycoproteins or glycolipids. Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are involved in pathologies associated with the inflammatory process, cell proliferation, adhesion, migration, and apoptosis. Recent evidence has shown that the administration of Amyloid-β 25-35 (Aβ 25-35 ) into the hippocampus of rats increases the inflammatory response that is associated with memory impairment and neurodegeneration. Galectins could participate in the modulation of the neuroinflammation induced by the Aβ 25-35 . The aim of this study was to evaluate the presence of Gal-1 and Gal-3 in the neuroinflammation induced by administration of Aβ 25-35 into the hippocampus and to examine spatial memory in the Morris water maze. After the administration of Aβ 25-35 , animals were tested for learning and spatial memory in the Morris water maze. Behavioral performance showed that Aβ 25-35 didn't affect spatial learning but did impair memory, with animals taking longer to find the platform. On the day 32, hippocampus was examined for astrocytes (GFAP), microglia (Iba1), Gal-1 and Gal-3 via immunohistochemical analysis, and the cytokines IL-1β, TNF-α, IFN-γ by ELISA. This study's results showed a significant increase in the expression of Gal-3 in the microglia and astrocytes, while Gal-1 didn't increase in the dorsal hippocampus. The expression of galectins is associated with increased cytokines in the hippocampal formation of Aβ 25-35 treated rats. These findings suggest that Gal-3 could participate in the inflammation induced by administration of Aβ 25-35 and could be involved in the neurodegeneration progress and memory impairment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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. Adult male Wistar rats were administered 6-OHDA into the dorso-lateral striatum, and the effects of Hc-TeTx fragment (20 μg/kg i.m. every 24 h) for 3 days; PPX (1 mg/kg p.o., every 12 h) for 30 days and their combination on various motor and neurochemical parameters were evaluated. Behavioral tests were carried out at 15 and 30 days post-treatments. At day 31, the animals were sacrificed and the levels of tyrosine hydroxylase (TH), reflecting dopaminergic activity in both striatum and substantia nigra, were evaluated. In addition, indices of astrogliosis, microgliosis, as well as oxidative stress in the striatum were determined. Both Hc-TeTx and PPX ameliorated the motor and neurochemical deficits induced by 6-OHDA lesion; however, the combination of the two drugs was not superior to each alone. Hence, at concentrations used in this study, no significant advantage in combining Hc-TeTx with PPX was noted. Although the results suggest similar neurochemical effects of the two compounds, further evaluation of different concentrations of Hc-TeTx and PPX as potential intervention in PD is warranted.

Memory impairment by the Amyloid-β 25-35 (Aβ 25-35 ) peptide in animal models has provided an understanding of the causes behind the similar deterioration that occurs in Alzheimer's disease. However, it is uncertain if a decrease of dendritic spines and neurogenesis conduces to cognitive impairment by an impairment in the retrieval of stored memory. The aim of this study was to evaluate the consequences of impairment on spatial memory caused by the administration of the Aβ 25-35 peptide in the hippocampus, which is associated whit morphological changes and neurogenesis in the dentate gyrus (DG). The vehicle or Aβ 25-35 peptide (0.1μg/μL) were bilaterally administered in the CA1 subfield of the rat hippocampus. The animals were tested for spatial learning and memory in the Morris Water Maze. In the day's 11, 18 and 32 after administration of the Aβ 25-35 peptide were examined the morphological changes in the DG using a Golgi-Cox stain. In the day 32, the neurogenesis was evaluated by the immunoreactivity to 5-bromo-2'-deoxyuridine (BrdU; 100mg/kg, i.p.) that corresponding to cellular proliferation post damage, the neuronal specific nuclear protein (NeuN) and doublecortin (DCX). This study found a memory retrieval impairment occurring at day 17, a cognitive deficit which had increased significantly at day 31 after the administration of Aβ 25-35 peptide. These results are related to morphological changes in the granular cells of the DG, such as a shorter dendritic length and a decrease in the number of dendritic spines. In neurogenesis, the total number of cells positive to BrdU, NeuN and DCX in the hippocampal granule cell layer was found to have declined in animals treated with Aβ 25-35 . The results suggest that the Aβ 25-35 peptide impairs memory retrieval by decreasing the number of dendritic spines and altering neurogenesis in the DG., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The recombinant C-terminal domain of tetanus toxin (Hc-TeTx) is a new non-toxic peptide of the tetanus toxin that exerts a protective action against glutamate excitotoxicity in motoneurons. Moreover, its efficacy as a neuroprotective agent has been demonstrated in several animal models of neurodegeneration. The eleven amino acids in the β amyloid peptide (Aβ25-35) mimic the toxic effects of the full β amyloid peptide (Aβ1-42), causing the impairment of the cholinergic system in the medial septum (MS) which, in turn, alters the septo-hippocampal pathway and leads to learning and memory impairments. The aim of this study was to examine the neuroprotective effects of the Hc-TeTx fragment against cholinotoxicity. The Hc-TeTx fragment (100 ng) was injected into the rats intercranially, with the Aβ(25-35) (2 μg) then injected into their MS. The animals were tested for spatial learning and memory in the eight-arm radial maze. The brains were removed to assess cholinergic markers, such as choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and to explore neurodegeneration in the MS and hippocampus, using amino-cupric silver and H&E staining. Finally, capase-3, a marker of apoptosis, was examined in the MS. Our results clearly demonstrate that the application of Hc-TeTx prevents the loss of cholinergic markers (ChAT and AChE), the activation of capase-3, and neurodegeneration in the MS and the CA1 and CA3 subfields of the hippocampus. All these improvements were reflected in spatial learning and memory performance, and were significantly higher compared with animals treated with Aβ(25-35). Interestingly, the single administration of Hc-TeTx into the MS modified the ChAT and AChE expression that affect cognitive processes, without inducing neurodegeneration or an increase in capase-3 expression in the MS and hippocampus. In summary, our findings suggest that the recombinant Hc-TeTx fragment offers effective protection for the septo-hippocampal pathway, given that it reduces the neurodegeneration caused by Aβ(25-35) and improves learning and memory processes., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Molecular chaperones, or heat shock proteins (HSP), have been implicated in numerous neurodegenerative disorders characterized by the accumulation of protein aggregates, such as Alzheimer disease. The agglomeration of insoluble structures of Aβ is thought to be responsible for neuronal death, which in turn leads to the loss of cognitive functions. Recent findings have shown that the induction of HSP decreases the level of abnormal protein aggregates, as well as demonstrating that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an analogue of geldanamycin (GA), increases Aβ clearance through the induction of molecular chaperones in cell culture. In light of this discovery that HSP overexpression can be neuroprotective, the search for a way to pharmacologically induce the overexpression of HSP and other associated chaperones may lead to a promising approach for the treatment of neurodegenerative diseases. The aim of our study was to evaluate both the effect of 17-AAG on the cognitive process and the HSP response in rats injected with Aβ25-35 into the CA1 of the hippocampus. The results show that the injection of Aβ caused a significant increase in the expression of the HSP involved in the regulation of cellular proteostasis. While the HSP did not reverse excitotoxic damage, given that experimental subjects showed learning and memory deficits, the administration of 17-AAG prior to the injection of Aβ25-35 did show an improvement in the behavioral assessment that correlated with the upregulation of HSP70 in subjects injured with Aβ. Overall, our data shows that the pharmacological induction of HSP using 17-AAG may be an alternative treatment of neurodegenerative diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) is a peptide that has a neuroprotective action against dopaminergic damage by MPP(+), both in vitro and in vivo. The trophic effects of Hc-TeTx have been related to its ability to activate the pathways of the tropomyosin receptor kinase, which are crucial for survival process. Our group had previously shown neuroprotective effect of intramuscular Hc-TeTx treatment on animals with a dopaminergic lesion; however, there is no evidence indicating its restorative effects on advanced dopaminergic neurodegeneration. The aim of our study was to examine the restorative effects of an intramuscular injection of the Hc-TeTx fragment on the nigrostriatal system of hemiparkinsonian rats. The animals were administered with a vehicle or Hc-TeTx (20μg/kg) in the gastrocnemius muscle for three consecutive days post-dopaminergic lesion, which was made using 6-hydroxydopamine. Post-Hc-TeTx treatment, the hemiparkinsonian rats showed constant motor asymmetry. Moreover, the ipsilateral striatum of the post-Hc-TeTx group had a lower number of argyrophilic structures and a major immunorreactivity to Tyrosine Hydroxylase in the striatum and the substantia nigra pars compacta compared to the 6-OHDA group. Our results show the restorative effect of the Hc-TeTx fragment during the dopaminergic neurodegeneration caused by 6-OHDA., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

We have previously shown that the intrastriatal injection of the C-terminal domain of tetanus toxin (Hc-TeTx) protects the nigrostriatal-dopaminergic pathways and improves motor behavior in hemiparkinsonism-rat models caused by MPP(+) (1-methyl-4-phenylpyridinium). Here we have investigated the protective effects of the intramuscular application of the Hc-TeTx on motor asymmetry and neurodegeneration in the striatum of 6-hydroxydopamine (6-OHDA)-treated rats. Adult male rats were intramuscularly injected with the recombinant Hc-TeTx protein (0.1-20μg/kg, daily) 3days before the stereotaxic injection of 6-OHDA into the left striatum. Our results showed that the motor-improvement functions were extended for 4weeks in all Hc-TeTx-treated groups, obtaining the maximum performance with the highest dose of Hc-TeTx (20μg/kg). The improvements found were 97%, 87%, and 70% in the turning behavior, stepping test, and cylinder test, respectively. The striatal levels of dopamine and its metabolites did not vary compared to the control group. Moreover, the peripheral treatment with Hc-TeTx in rats prevents, for 30days, the neurodegeneration in the striatum caused by the toxicity of the 6-OHDA. Our results lead us to believe that the Hc-TeTx could be a potential therapeutic agent in pathologies caused by impairment of dopaminergic innervations such as Parkinson's disease., (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Sialic acid in glycoconjugates participates in important cellular functions associated with normal development, growth, and communication. Therefore we evaluated the sialylation pattern and memory deficits caused by the injection of Aβ((25-35)) into the hippocampus (Hp) of rats. The eight-arm maze spatial-learning and memory test indicated that the injection of Aβ((25-35)) into subfield CA1 of the Hp impaired both learning and memory. The sialylation pattern was examined using sialic acid-specific lectins. Our results showed that Maackia amurensis agglutinin (MAA, specific for Neu5Acα2,3Gal) showed reactivity in the CA1 and dentate gyrus (DG) subfields of the Hp mainly in the group injected with vehicle, whereas Macrobrachium rosenbergii lectin (MRL, specific for Neu5,9,7Ac) and Sambucus nigra agglutinin (SNA, specific for Neu5Acα2,6Gal-GalNAc) had increased reactivity in the CA1 and DG subfields of the Hp in the Aβ((25-35))-injected group. The staining pattern of the antibody specific for polysialic acid (a linear homopolymer of α-2,8-linked sialic acid) increased in the CA1 and DG subfields of the Hp of the Aβ((25-35)) group compared to the control group. Our results suggest that injection of Aβ((25-35)) causes impairment in spatial memory and alters the sialylation pattern in response to compensatory reorganization and-or sprouting of dendrites and axons of the surviving neurons., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Alzheimer's disease (AD) is characterized by the amyloid-beta (Abeta) aggregation but it is unclear when this process begins. Previously, we showed that amyloid-beta(25-35) (Abeta(25-35)) increases the nitric oxide (NO) pathways and causes neurodegenerative effects in rats. The excessive increase of NO during brain development can promote a persistent oxidative stress, but the role of the Abeta(25-35) in the neonatal age and its effects over the long term is unclear. Our aim was to evaluate if the Abeta(25-35) injection on postnatal day 7 causes loss in spatial memory by NO pathways in adult rats. Our results showed that neonatal-Abeta(25-35) injection into the hippocampus (Hp) causes significant impairments in the spatial memory after 90 days. The NO levels were found increased and argynophilic in the Hp. Other evidence of neuronal damage was an increase of the immunoreactivity for 3-nitrotyrosine (3-NT) and the glial-fibrilar acid protein (GFAP) in the Hp of the Abeta(25-35) group. In contrast, these effects were blocked by the administration of L-NAME (inhibitor of nitric oxide synthase) before the injection of Abeta(25-35). The L-NAME plus Abeta(25-35) group showed a better performance in the spatial memory compared to the Abeta(25-35) group. In addition in this group we found a decrease of NO, 3-NT and neurodegeneration in the Hp compared to the Abeta(25-35) group. This finding is a novel result about the role of Abeta(25-35) during the neonatal stage that enhances the NO production, which appears to impair the spatial memory in adult rats.

Recently it has been shown that the C-terminus fragment of the tetanus toxin (Hc-TeTx) is transported retrogradely and had shown neuroprotective effects, preventing neuronal death by apoptosis. This could be a new alternative preventing ongoing cell death and restoring the motor function in Parkinson's disease (PD), which is characterized by dopaminergic neurodegeneration. Our aim was to evaluate the effects of local administration of Hc-TeTx on motor behavior and the dopamine (DA) levels in the striatum of MPP(+)-treated rats. In the rotational behavior task, the Hc-TeTx [2 microM]+MPP(+) group had a decreased number of contralateral rotations and the cylinder test improved for both forelimb-use asymmetry compared to the MPP(+) group. The staircase test showed that the Hc-TeTx+MPP(+) group had an improvement of fine motor skills compared to the same limb performance of the MPP(+) group. The group of animals with Hc-TeTx+MPP(+) had higher DA and metabolite levels compared to the MPP(+) group. Our study clearly shows that Hc-TeTx improves different motor behavior strongly, which favors the hypothesis of the Hc-TeTx fragment enhancing survival pathways that result in amelioration of the dopaminergic system of rats with a dopaminergic lesion.

beta-Amyloid plays an important role in the neurodegeneration process of Alzheimer's disease (AD), but its neurotoxic mechanisms are not clear. It has been associated with the increase of oxidative stress and cognitive impairment because the beta-amyloid peptide 25-35 (Abeta((25-35))) has the critical neurotoxic properties of the full-length Abeta(1-42). Our present study shows the role of Abeta((25-35)) when injected into the temporal cortex on the nitric oxide pathways, 3-nitrotyrosine, neuronal death, and the spatial memory of rats 1 month after the injection. Our data showed that Abeta((25-35)) increases oxidative stress, causes neuronal damage, and decreases spatial memory in rats. Notably, the injection of the fraction Abeta((25-35)) caused an increase of nNOS and iNOS immunoreactivity in the temporal cortex and hippocampus. We demonstrated a significant increase of reactive astrocytosis, which was accompanied by neuronal damage in the temporal cortex and hippocampus of rats injected with Abeta((25-35)). These data suggest that the fraction Abeta((25-35)) injected into the temporal cortex might contribute to understanding the role of nitric oxide on the biological changes related to the neuropathological progression and the memory impairment in AD.