Prophylactic zinc and therapeutic selenium administration in adult rats prevents long-term cognitive and behavioral sequelae by a transient ischemic attack.

The transient hypoxic-ischemic attack, also known as a minor stroke, can result in long-term neurological issues such as memory loss, depression, and anxiety due to an increase in nitrosative stress. The individual or combined administration of chronic prophylactic zinc and therapeutic selenium is known to reduce nitrosative stress in the first seven days post-reperfusion and, due to an antioxidant effect, prevent cell death. Besides, zinc or selenium, individually administered, also causes antidepressant and anxiolytic effects. Therefore, this work evaluated whether combining zinc and selenium could prevent stroke-elicited cognition and behavior deficits after 30 days post-reperfusion. Accordingly, we assessed the expression of growth factors at 7 days post-reperfusion, a four-time course of memory (from 7 to 28 days post-learning test), and cell proliferation, depression, and anxiety-like behavior at 30 days post-reperfusion. Male Wistar rats with a weight between 190 and 240 g) were treated with chronic prophylactic zinc administration with a concentration of 0.2 mg/kg for 15 days before common carotid artery occlusion (10 min) and then with therapeutic selenium (6 µg/kg) for 7 days post-reperfusion. Compared with individual administrations, the administration combined of prophylactic zinc and therapeutic selenium decreased astrogliosis, increased growth factor expression, and improved cell proliferation and survival in two regions, the hippocampus, and cerebral cortex. These effects prevented memory loss, depression, and anxiety-like behaviors. In conclusion, these results demonstrate that the prophylactic zinc administration combined with therapeutic selenium can reduce the long-term sequelae caused by the transient ischemic attack. Significance statement. A minor stroke caused by a transient ischemic attack can result in psychomotor sequelae that affect not only the living conditions of patients and their families but also the economy. The incidence of these micro-events among young people has increased in the world. Nonetheless, there is no deep understanding of how this population group responds to regular treatments (Ekker and et al., 2018) [1]. On the basis that zinc and selenium have antioxidant, anti-inflammatory, and regenerative properties in stroke animal models, our work explored whether the chronic combined administration of prophylactic zinc and therapeutic selenium could prevent neurological sequelae in the long term in a stroke rat model of unilateral common carotid artery occlusion (CCAO) by 10-min. Our results showed that this combined treatment provided a long-term neuroprotective effect by decreasing astrogliosis, memory loss, anxiety, and depression-like behavior.

ß-Secretase-1: In Silico Drug Reposition for Alzheimer's Disease.

The ß-secretase-1 enzyme (BACE-1) performs a key role in the production of beta-Amyloid protein (Aß), which is associated with the development of Alzheimer's disease (AD). The inhibition of BACE-1 has been an important pharmacological strategy in the treatment of this neurodegenerative disease. This study aims to identify new potential candidates for the treatment of Alzheimer's with the help of in silico studies, such as molecular docking and ADME prediction, from a broad list of candidates provided by the DrugBank database. From this analysis, 1145 drugs capable of interacting with the enzyme with a higher coupling energy than Verubecestat were obtained, subsequently only 83 presented higher coupling energy than EJ7. Applying the oral route of administration as inclusion criteria, only 41 candidates met this requirement; however, 6 of them are associated with diagnostic tests and not treatment, so 33 candidates were obtained. Finally, five candidates were identified as possible BACE-1 inhibitors drugs: Fluphenazine, Naratriptan, Bazedoxifene, Frovatriptan, and Raloxifene. These candidates exhibit pharmacophore-specific features, including the indole or thioindole group, and interactions with key amino acids in BACE-1. Overall, this study provides insights into the potential use of in silico methods for drug repurposing and identification of new candidates for the treatment of Alzheimer's disease, especially those targeting BACE-1.

Obese male Zucker rats exhibit dendritic remodeling in neurons of the hippocampal trisynaptic circuit as well as spatial memory deficits.

Obesity is characterized by excessive fat accumulation. The Zucker rat displays genetic obesity due to a mutation in the leptin receptor gene; this model is of great interest because of its similarity to human obesity. Brain regions may be affected by obesity, but detailed information is lacking. In the present study, we analyzed the morphology of neurons in the hippocampal trisynaptic circuit as well as the spatial memory of obese Zucker rats. We performed two experiments. Each experiment contained two experimental groups: the control group (male Long Evans rats) and the study group (obese male Zucker rats). We monitored the body weights of all rats over 4 weeks. In the first experiment, we analyzed the morphology of hippocampal neurons. Under anesthesia, we measured the abdominal and hip circumferences and collected at least 1 ml of blood to assess serum glucose (GLU), triglyceride (TGC), and cholesterol (COL) concentrations. We perfused the brains of these rats with 0.9% saline solution, incubated the brains in Golgi-Cox solution, and subsequently evaluated the morphology of pyramidal neurons in the hippocampus (the CA1-CA3 regions) and the entorhinal cortex as well as the morphology of granule neurons in the dentate gyrus. In the second experiment, we assessed the spatial memory of animals with the Morris water maze. The Zucker rats had an obese phenotype, as indicated by their elevated body weight and increased abdominal and hip circumferences as well as elevated GLU, COL, and TGC concentrations. Analysis of neurons from the specified regions in obese male Zucker rats indicated reduced dendritic arborization and reduced dendritic spine density. In terms of spatial learning and memory, the obese Zucker rats exhibited intact spatial learning (i.e., of platform location) but deficits in spatial memory. These data provide evidence that obesity alters the morphology and function of hippocampal neurons.

Sources of antibiotics pollutants in the aquatic environment under SARS-CoV-2 pandemic situation.

During the last decades, the growth of concern towards different pollutants has been increasing due to population activities in large cities and the great need for food production by the agri-food industry. The effects observed in specific locations have shown the impact over the environment in air, soil and water. Specifically, the current pandemic of COVID-19 has brought into the picture the intensive use of different medical substances to treat the disease and population intensive misuse. In particular, the use of antibiotics has increased during the last 20 years with few regulations regarding their excessive use and the disposal of their residues from different sources. Within this review, an overview of sources of antibiotics to aquatic environments was done along with its impact to the environment and trophic chain, and negative effects of human health due prolonged exposure which endanger the environment, population health, water, and food sustainability. The revision indicates the differences between sources and its potential danger due toxicity, and accumulation that prevents water sustainability in the long run.

Inhibitory mechanism of 17ß-aminoestrogens in the formation of Aß aggregates.

Alzheimer's disease (AD) is a complex neurodegenerative disorder associated with the aggregation of the amyloid-beta peptide (Aß) into large oligomers and fibrils that damage healthy brain cells. The predominant peptide fragments in the plaques are mainly formed by the Aß1-40 and Aß1-42 peptides, albeit the eleven-residue Aß25-35 segment is largely used in biological studies because it retains the neurotoxic properties of the longer Aß peptides. Recent studies indicate that treatment with therapeutic steroid hormones reduces the progress of the disease in AD models. Particularly, treatment with 17ß-aminoestrogens (AEs) has shown a significant alleviation of the AD development by inhibiting oxidative stress and neuronal death. Yet, the mechanism by which the AE molecules exhibit their beneficial effects remains speculative. To shed light into the molecular mechanism of inhibition of the AD development by AEs, we investigated the possibility of direct interaction with the Aß25-35 peptide. First, we calculate various interacting electronic properties of three AE derivatives as follows: prolame, butolame, and pentolame by performing DFT calculations. To account for the polymorphic nature of the Aß aggregates, we considered four different Aß25-35 systems extracted from AD relevant fibril structures. From the calculation of different electron density properties, specific interacting loci were identified that guided the construction and optimization of various complexes. Interestingly, the results suggest a similar inhibitory mechanism based on the direct interaction between the AEs and the M35 residue that seems to be general and independent of the polymorphic properties of the Aß aggregates. Our analysis of the complex formation provides a structural framework for understanding the AE therapeutic properties in the molecular inhibitory mechanism of Aß aggregation.

Peripheral Administration of Tetanus Toxin Hc Fragment Prevents MPP+ Toxicity In Vivo.

Several studies have shown that intrastriatal application of 1-methyl-4-phenylpyridinium (MPP+) produces similar biochemical changes in rat to those seen in Parkinson's disease (PD), such as dopaminergic terminal degeneration and consequent appearance of motor deficits, making the MPP+ lesion a widely used model of parkinsonism in rodents. Previous results from our group have shown a neuroprotective effect of the carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) under different types of stress. In the present study, pretreatment with the intraperitoneal injection of Hc-TeTx in rats prevents the decrease of tyrosine hydroxylase immunoreactivity in the striatum due to injury with MPP+, when applied stereotaxically in the striatum. Similarly, striatal catecholamine contents are restored, as well as the levels of two other dopaminergic markers, the dopamine transporter (DAT) and the vesicular monoamine transporter-2 (VMAT-2). Additionally, uptake studies of [3H]-dopamine and [3H]-MPP+ reveal that DAT action is not affected by Hc-TeTx, discarding a protective effect due to a reduced entry of MPP+ into nerve terminals. Behavioral assessments show that Hc-TeTx pretreatment improves the motor skills (amphetamine-induced rotation, forelimb use, and adjusting steps) of MPP+-treated rats. Our results lead us to consider Hc-TeTx as a potential therapeutic tool in pathologies caused by impairment of dopaminergic innervation in the striatum, as is the case of PD.

Neuroinflammation induced by amyloid ß25-35 modifies mucin-type O-glycosylation in the rat's hippocampus.

Amyloid-ß (Aß) plays a relevant role in the neurodegenerative process of Alzheimer's disease (AD). The 25-35 peptide of amyloid-ß (Aß25-35) induces the inflammatory response in brain experimental models. Mucin-type O-glycosylation has been associated with inflammation of brain tissues in AD, thus in this work, we aimed at identifying changes in the glycosylation profile generated by the injection of Aß25-35 into the CA1 of the hippocampus of rats, using histochemistry with lectins. Our results indicate that 100µM Aß25-35 induce increased recognition of the Amaranthus leucocarpus lectin (ALL) (specific for Galß1,3-GalNAcα1,0-Ser/Thr); whereas concanavalin A (Con A) (specific for α-Man) showed no differences among treated and control groups of rats. Jacalin and peanut agglutinin (Galß1,3GalNAcα1,0-Ser/Thr) showed no recognition of brain cells of control or treated rats. After 6-h treatment of the tissue with trypsin or with 200mM GalNAc, the interaction with ALL was inhibited. Immunohistochemistry showed positive anti-NeuN and ALL-recognition of neurons; however, anti-GFAP and anti-CD11b showed no co-localization with ALL. The ALL+ neurons revealed the presence of cytochrome C in the cytosol and active caspase 3 in the cytosol and nucleus. Administration of the interleukin-1 receptor antagonist (IL-1RA) to Aß25-35-treated rats diminished neuroinflammation and ALL recognition. These results suggest a close relationship among over-expression of mucin-type O-glycosylation, the neuroinflammatory process, and neuronal death.

Effect of amyloid-Β (25-35) in hyperglycemic and hyperinsulinemic rats, effects on phosphorylation and O-GlcNAcylation of tau protein.

Aggregation of the amyloid beta (Aß) peptide and hyperphosphorylation of tau protein, which are markers of Alzheimer's disease (AD), have been reported also in diabetes mellitus (DM). One regulator of tau phosphorylation is O-GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation and phosphorylation of tau protein were evaluated in the brain of rats with streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with the Aß25-35 peptide in the hippocampal region CA1. Weight, glycated hemoglobin, glucose, and insulin were determined. Male Wistar rats were divided in groups (N=20): a) control, b) treated only with the Aß25-35 peptide, c) treated with Aß25-35 and STZ, and d) treated only with STZ. Results showed statistically significant differences in the mean weight, glucose levels, insulin concentration, and HbA1c percentage, between C- and D-treated groups and not STZ-treated A and B (P<0.05). Interestingly, our results showed diminution of O-GlcNAcylation and increase in P-tau-Ser-396 in the hippocampal area of the Aß25-35- and STZ-treated groups; moreover, enhanced expression of GSK3beta was observed in this last group. Our results suggest that hyperinsulinemia-Aß25-35-hyperglycemia is relevant for the down regulation of O-GlcNAcylation and up-regulation of the glycogen synthase kinase-3 beta (GSK3beta), favoring Aß25-35-induced neurotoxicity in the brain of rats.

Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model.

Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.

Unilateral injection of Aß25-35 in the hippocampus reduces the number of dendritic spines in hyperglycemic rats.

Alzheimer's disease (AD) is a neurodegenerative process exacerbated by several risk factors including impaired glucose metabolism in the brain that could cause molecular and neurochemical alterations in cognitive regions such as the hippocampus (Hp). Consequently, this process could cause neuronal morphological changes; however, the mechanism remains elusive. We induced chronic hyperglycemia after streptozotocin (STZ) administration. Then, we examined spatial learning and memory using the Morris water maze test and evaluated neuronal morphological changes using the Golgi-Cox stain procedure in hyperglycemic rats that received a Aß25-35 unilateral injection into the Hp. Our results demonstrate that STZ combined with Aß25-35 induced significant deficits in the spatial memory. In addition, we observed a significant reduction in the number of dendritic spines of pyramidal neurons in the dorsal Hp of rats with STZ plus Aß25-35 . In conclusion, the reduced spine density of pyramidal neurons in the CA1 dorsal Hp could produce the spatial memory deficit observed in these animals. These results suggest that hyperglycemia can trigger Aß-induced neurodegeneration and thus the appearance of AD symptoms would be accelerated. Synapse 68:585-594, 2014. © 2014 Wiley Periodicals, Inc.

Aminoguanidine treatment ameliorates inflammatory responses and memory impairment induced by amyloid-beta 25-35 injection in rats.

Alzheimer disease (AD) is a neurodegenerative disorder caused by accumulation of the amyloid-beta peptide (Aß) in neuritic plaques. Its neurotoxic mechanisms are associated with inflammatory responses and nitrosative stress generation that promote expression of inducible nitric oxide synthase (iNOS) and increased nitric oxide causing neuronal death and memory impairment. Studies suggest that treatment with anti-inflammatory and anti-oxidant agents decreases the risk of developing AD. Aminoguanidine (AG) is an iNOS inhibitor with anti-inflammatory and anti-oxidant effects. In this study, we evaluated the effects of systemic administration of AG (100 mg/kg/day for 4 days) on spatial memory and inflammatory responses induced by an injection of Aß(25-35) [100 µM] into the temporal cortex (TCx) of rats. A significant improvement of spatial memory was evident in the Aß(25-35)-treated group at day 30 post-injection subjected to AG treatment; this effect was correlated with decreases in reactive gliosis, IL-1ß, TNF-α, and nitrite levels, as well as a reduction in neurodegeneration in the TCx and hippocampus (Hp). These results suggest that AG treatment inhibited glia activation and cytokine release, which may help to counteract neurodegenerative events induced by the toxicity of Aß.

Chronic administration of nicotine enhances NMDA-activated currents in the prefrontal cortex and core part of the nucleus accumbens of rats.

Nicotine is an addictive substance of tobacco. It has been suggested that nicotine acts on glutamatergic (N-methyl-d-aspartate, NMDA) neurotransmission affecting dopamine release in the mesocorticolimbic system. This effect is reflected in neuroadaptative changes that can modulate neurotransmission in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) core (cNAcc) and shell (sNAcc) regions. We evaluated the effect of chronic administration of nicotine (4.23 mg/kg/day for 14 days) on NMDA activated currents in dissociated neurons from the PFC, and NAcc (from core and shell regions). We assessed nicotine blood levels by mass spectrophotometry and we confirmed that nicotine increases locomotor activity. An electrophysiological study showed an increase in NMDA currents in neurons from the PFC and core part of the NAcc in animals treated with nicotine compared to those of control rats. No change was observed in neurons from the shell part of the NAcc. The enhanced glutamatergic activity observed in the neurons of rats with chronic administration of nicotine may explain the increased locomotive activity also observed in such rats. To assess one of the possible causes of increased NMDA currents, we used magnesium, to block NMDA receptor that contains the NR2B subunit. If there is a change in percent block of NMDA currents, it means that there is a possible change in expression of NMDA receptor subunits. Our results showed that there is no difference in the blocking effect of magnesium on the NMDA currents. The magnesium lacks of effect after nicotinic treatment suggests that there is no change in expression of NR2B subunit of NMDA receptors, then, the effect of nicotine treatment on amplitude of NMDA currents may be due to an increase in the quantity of receptors or to a change in the unitary conductance, rather than a change in the expression of the subunits that constitute it.

Amyloid-ß(25-35) induces a permanent phosphorylation of HSF-1, but a transitory and inflammation-independent overexpression of Hsp-70 in C6 astrocytoma cells.

Two hallmarks of Alzheimer diseases are the continuous inflammatory process, and the brain deposit of Amyloid b (Aß), a cytotoxic protein. The intracellular accumulation of Aß(25-35) fractions, in the absence of Heat Shock proteins (Hsps), could be responsible for its cytotoxic activity. As, pro-inflammatory mediators and nitric oxide control the expression of Hsps, our aim was to investigate the effect of Aß(25-35) on the concentration of IL-1ß, TNF-α and nitrite levels, and their relation to pHSF-1, Hsp-60, -70 and -90 expressions, in the rat C6 astrocyte cells. Interleukin-specific ELISA kits, immunohistochemistry with monoclonal anti-Hsp and anti pHSF-1 antibodies, and histochemistry techniques, were used. Our results showed that Aß25-35 treatment of C6 cells increased, significantly and consistently the concentration of IL-1ß, TNF-α and nitrite 3 days after initiating treatment. The immunoreactivity of C6 cells to Hsp-70 reached its peak after 3 days of treatment followed by an abrupt decrease, as opposed to Hsp-60 and -90 expressions that showed an initial and progressive increase after 3 days of Aß(25-35) treatment. pHSF-1 was identified throughout the experimental period. Nevertheless, progressive and sustained cell death was observed during all the treatment times and it was not caspase-3 dependent. Our results suggest that Hsp-70 temporary expression serves as a trigger to inhibit casapase-3 pathway and allow the expression of Hsp-60 and -90 in C6 astrocytoma cells stimulated with Aß(25-35).

Neuroprotective effect of the aminoestrogen prolame against impairment of learning and memory skills in rats injected with amyloid-ß-25-35 into the hippocampus.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by the deposition of the amyloid-beta peptide (Aß) in senile plaques and cerebral vasculature. Its neurotoxic mechanisms are associated with the generation of oxidative stress and reactive astrogliosis that cause neuronal death and memory impairment. Estrogens reduce the rate of Azheimer's disease because of their antioxidant activity. Prolame (N-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-3-hydroxypropylamine) is an aminoestrogen with estrogenic and antithrombotic effects. In our study we evaluated the role of prolame on Aß(25-35)-caused oxidative stress, reactive astrogliosis, and impairment of spatial memory(.) The Aß(25-35) (100 µM/µl) or vehicle was injected into the CA1 subfield of the hippocampus of the rat. The subcutaneous injection of prolame (400 µl, 50 nM) or sesame oil (400 µl) started 1 day before the Aß(25-35) injection and was continued for another 29 days. The results showed a significant impairment of spatial memory evident 30 days after the Aß(25-35) injection. The prolame treatment significantly reduced spatial-memory impairment and decreased lipid peroxidation, reactive oxygen species, and reactive gliosis. It also restored the eNOS and nNOS expression to normal levels. In conclusion the aminoestrogen prolame should be considered as an alternative in the treatment of Alzheimer's disease.

Aß25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats.

Amyloid-ß (Aß)25-35 is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aß25-35 into the temporal cortex (TCx) of rats increases the inflammatory response; however, it is unclear how the inflammatory process could be involved in the progression of Aß25-35 toxicity. In this study we investigated the role of inflammation in the neuronal damage and spatial memory impairment generated by Aß25-35 in rat TCx using immunohistochemistry, ELISA, and a behavioral test in the radial maze. Our findings show that Aß25-35 -injection into the TCx induced a reactive gliosis (GFAP and CD11b-reactivity) and an increase of pro-inflammatory cytokines (IL-1ß, IL-6, IL-17, and TNF-α) in the TCx and the hippocampus at 5, 15, and 30 days after injection. Thirty days after Aß25-35 injection, we observed that the inflammatory reaction probably contributed to increase the immunoreactivity of inducible nitric oxide synthase and nitrite levels, as well as to the loss of neurons in TCx and hippocampus. Behavioral performance showed that the neurodegeneration evoked by Aß25-35 delayed acquisition of learning and impaired spatial memory, because the Aß25-35-treated animals showed a greater number of errors during the task than the control group. Previous administration of an interleukin receptor antagonist (IL-1ra) (10 and 20 µg/µL, into TCx), an anti-inflammatory agent, suppressed the Aß25-35-induced inflammatory response and neurodegeneration, as well as memory dysfunction. This study suggests that the chronic inflammatory reaction could contribute to the progression of Aß25-35 toxicity and cause cognitive impairment.

Sialylated and O-glycosidically linked glycans in prion protein deposits in a case of Gerstmann-Sträussler-Scheinker disease.

Prion diseases are caused by an abnormal form of the prion protein (PrP(Sc)). We identified, with lectins, post-translational modifications of brain proteins due to glycosylation in a Gerstmann-Sträussler-Scheinker (GSS) patient. The lectin Amaranthus leucocarpus (ALL), specific for mucin type O-glycosylated structures (Galß1,3 GalNAcα1,0 Ser/Thr or GalNAcα1,0 Ser/Thr), and Sambucus nigra agglutinin (SNA), specific for Neu5Acα2,6 Gal/GalNAc, showed positive labeling in all the prion deposits and in the core of the PrP(Sc) deposits, respectively, indicating specific distribution of O-glycosylated and sialylated structures. Lectins from Maackia amurensis (MAA, Neu5Acα2,3), Macrobrachium rosenbergii (MrL, Neu5,9Ac2-specific) and Arachis hypogaea (PNA, Gal-specific) showed low staining of prion deposits. Immunohistochemistry colocalization with prion antibody indicated that all lectins stained prion protein deposits. These results show that specific modifications in the glycosylation pattern are closely related to the hallmark lesions and might be an early event in neuronal degeneration in GSS disease.

Antioxidant effects of epicatechin on the hippocampal toxicity caused by amyloid-beta 25-35 in rats.

Amyloid-beta is involved in neurodegeneration in Alzheimer's disease. The Amyloid-beta fraction 25-35 (Amyloid-beta 25-35) is believed to cause neurotoxicity through oxidative stress. We evaluated the antioxidant effects of Epicatechin on the Abeta25-35-caused hippocampal toxicity in vivo. Biochemical and histological evaluations, and learning and memory tasks, were assessed. Amyloid-beta 25-35 (100 microM/microL) or vehicle was injected into the CA1 hippocampal region of the rat 5 h after a single oral dose of Epicatechin (30 mg/kg). Lipid peroxidation and reactive oxygen species formation were measured in Amyloid-beta- and Amyloid-beta-Epicatechin-treated groups at 2 h and 24 h after dosing and formation of the lesion. There was an increase in lipid peroxidation and reactive oxygen species formation at 2-h and 24-h postlesion. Learning and memory tests were made 27-30 days after surgery in independent groups under the same experimental conditions. Immunohistochemical detection of glial-fibrilar acidic protein (GFAP) was evaluated in hippocampal tissues from the animals 30-days postsurgery. Amyloid-beta 25-35 caused a significant increase in lipid peroxidation and reactive oxygen species and a decrease in memory skills. In addition, hippocampal tissues from Amyloid-beta 25-35-treated animals showed an increased immunoreactivity against GFAP. In contrast, animals pretreated with Epicatechin had a significant decrease in lipid peroxidation and reactive oxygen species and an improvement in memory skills. GFAP immunoreactivity was also decreased. Our results showed that Amyloid-beta 25-35-caused oxidative damage of the hippocampus was blocked by the administration of Epicatechin.

Lipid peroxidation, mitochondrial dysfunction and neurochemical and behavioural deficits in different neurotoxic models: protective role of S-allylcysteine.

Experimental evidence on the protective properties of S-allylcysteine (SAC) was collected from three models exerting striatal toxicity. In the first model, SAC (120 mg kg(-1)x5) prevented lipoperoxidation (LP) and mitochondrial dysfunction (MD) in synaptosomal fractions from 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridinium-treated mice (30 mg kg(-1)), but without complete restoration of dopamine levels. In the second model, SAC (300 mg kg(-1)x 3), prevented LP and MD in synaptosomes from rats infused with 6-hydroxydopamine (8 microg microl(-1)) into the substantia nigra pars compacta, but again, without total reversion of depleted dopamine levels. In the third model, SAC (100 mg kg(-1)x 1) prevented MD in synaptosomes from rats injected with 3-nitropropionic acid (10 mg kg(-1)), but in contrast to the other models, it failed to prevent LP. SAC also prevented the aberrant motor activity patterns evoked by the three toxins. Altogether, the results suggest that the antioxidant properties of SAC are responsible for partial or total preservation of neurochemical, biochemical and behavioural markers, indicating that pro-oxidant reactions underlie the neurotoxicity in these models.

Alterations in dendritic morphology of the prefrontal cortical and striatum neurons in the unilateral 6-OHDA-rat model of Parkinson's disease.

We have studied the morphological changes of the dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and the medium spiny neurons of the caudate-putamen (CPu) and nucleus accumbens (NAcc) induced by the injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). The unilateral 6-OHDA-induced lesion of the SNc was made in Wistar rats to produce the Parkinson model lesion. Two weeks after the injection, the testing of rotational behavior caused by amphetamine injection was done to assess the animals with lesions. Four weeks after the 6-OHDA injection, the morphology of the pyramidal cells of Layer 5 of the PFC and the medium spiny neurons of the CPu and NAcc were quantified by modified Golgi-Cox staining. The results showed that the length of dendrites, the branching, and the density of dendritic spines on the medium spiny neurons of the same side of the caudate-putamen lesion were significantly decreased in rats with the unilateral 6-OHDA-induced lesion of the SNc. The pyramidal neurons of the PFC and medium spiny neurons of the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. Our data suggest that the SNc lesion with the 6-OHDA, Hemiparkinsonism animal model may lead to altered neuronal plasticity in the CPu, NAcc, and PFC that may have participated in the emergence of the behavioral changes observed in these animals.

S-Allylcysteine prevents amyloid-beta peptide-induced oxidative stress in rat hippocampus and ameliorates learning deficits.

The effects of S-allylcysteine on oxidative damage and spatial learning and memory deficits produced by an intrahippocampal injection of amyloid-beta peptide 25-35 (Abeta(25-35)) in rats were investigated. The formation of reactive oxygen species, lipid peroxidation and the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were all measured in hippocampus 120 min after Abeta(25-35) injection (1 microl of 100 microM solution), while learning and memory skills were evaluated 2 and 35 days after the infusion of Abeta(25-35) to rats, respectively. Abeta(25-35) increased both reactive oxygen species and lipid peroxidation, whereas pretreatment with S-allylcysteine (300 mg/kg, i.p.) 30 min before peptide injection decreased both of these markers. In addition, Abeta(25-35)-induced incorrect learning responses were prevented in most of trials by S-allylcysteine. In contrast, enzyme activities were found unchanged in all groups tested. Findings of this work: (i) support the participation of reactive oxygen species in Abeta(25-35)-induced hippocampal toxicity and learning deficits; and (ii) suggest that the protective effects of S-allylcysteine were related to its ability to scavenge reactive oxygen species.