Effects Of Chronic Aluminum Exposure Research Articles

Effects of Chronic Aluminum Lactate Exposure on Neuronal Apoptosis and Hippocampal Synaptic Plasticity in Rats.

This study investigated the effects of chronic aluminum exposure on apoptosis of hippocampal neurons, and synaptic plasticity in the hippocampus in rats. Rats were divided into the control, low-dose (L-Al), mid-dose (M-Al), and high-dose (H-Al) groups. After chronic exposure of aluminum, the Morris water maze (MWM) and open-field (OF) tests were performed to assess the behavioral performance. Electrophysiological measurements were conducted. Flow cytometry was used to assess the apoptotic processes. Quantitative real-time PCR and ELISA were performed to measure mRNA and protein expression levels of caspases. After 90days of aluminum exposure, the aluminum contents in the brain of the rats were increased, with the increasing exposure dose. The MWM and OF tests showed that chronic exposure of aluminum significantly impaired the neurobehavior of rats. Moreover, after high-frequency stimulation (HFS), the average amplitudes of field excitatory postsynaptic potentials (fEPSPs) for the M-Al and H-Al groups were lower than the control group at 10, 20, 30, 40, 50, and 60min. Furthermore, the apoptotic rates in the M-Al and H-Al groups were significantly higher than the control group. The qRT-PCR and ELISA showed that, compared with the control group, the mRNA and protein expression levels of caspases-3, -8, and -9 were significantly increased in the aluminum-treated groups compared with the control group. Long-term exposure to aluminum could induce the apoptosis of hippocampal neurons, damage the synaptic plasticity, and impair the learning and memory functions in rats. There might be a close relationship between the neuronal apoptosis and synaptic plasticity damage.

Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in Sprague-Dawley (SD) rats. Thirty-two male SD rats were randomly and equally divided into 4 groups: control group and high-, middle-, and low-dose exposure groups. The rats in high-, middle-, and low-dose exposure groups were fed with the feed mixed with AlCl(3) (120.0, 12.0, and 1.2 mg/kg, respectively), while the rats in control group were fed conventionally. After 6 months of feeding, brain aluminum levels were determined by inductively coupled plasma mass spectrometry; Morris water maze was employed to test the learning and memory abilities; the expression and content of BDNF in brain tissue were measured by Western blot and enzyme-linked immuno sorbent assay (ELISA). The high- and middle-dose exposure groups had significantly higher brain aluminum levels than the control group (P<0.05). The Morris water maze test showed that the high- and middle-dose exposure groups had significantly prolonged escape latency (P<0.05), significantly prolonged time taken to first reach the target quadrant (P<0.01), and significantly decreased number of platform crossings and time spent in the target quadrant (P<0.05), as compared with the control group. The Western blot and ELISA showed that the expression and content of BDNF in brain tissue decreased as the dose of AlCl(3) increased, and they were significantly lower in the high- and middle-dose exposure groups than in the control group (P<0.05). Chronic aluminum exposure (12.0 and 120.0 mg/kg) can lead to cognitive dysfunction in rats, and the decreased expression of BDNF may be one of the mechanisms of learning and memory deficits induced by aluminum.

The effects of chronic aluminum exposure on learning and memory of rats by observing the changes of Ras/Raf/ERK signal transduction pathway

ObjectiveTo investigate the effects of chronic aluminum (Al) exposure on learning and memory function of rats by observing the changes of Ras/Raf/ERK (Ras/ERK) signaling pathway. MethodsEighty weaned Wistar rats were divided into four groups ad libitum, 20 rats in each group. The four groups were fed with drinking water containing 0% (control), 0.2%, 0.4% and 0.6% (Al exposure) AlCl3 for 3months individually to set up aluminum exposure models. The laboratory was maintained at 18–23°C and 45–55% relative humidity. Graphite furnace atomic absorption spectrometry was used to detect the content of Al in brain and blood. Western blot and real-time PCR (RT-PCR) were used to determine the protein and mRNA expression levels for Ras, Raf1, ERK2 and CREB. ResultsChronic Al exposure increased the content of Al in rats’ blood and brain. It increased expression of Ras in the hippocampi compared with the control but the expression decreased along the Al exposure groups (p<0.05). Similarly, Raf1, ERK2 and CREB expressions decreased compared to the control in a dose-dependent manner (p<0.05). ConclusionChronic Al exposure may affect learning and memory through impact on Ras/ERK signal pathway.

Effects of chronic aluminum exposure on memory through multiple signal transduction pathways

Objective To investigate the effects of chronic aluminum (Al) exposure on memory of rats by recording long-term potentiation (LTP) induction in CA1 region of Schaffer collateral (SC) of hippocampus and observing the changes of key LTP induction-related kinases. Methods Forty weaned Wistar rats were divided into 4 groups ad libitum, each group 10 rats. Three groups were fed with 0.2%, 0.4% and 0.6% AlCl 3 in drinking water for three months individually to set up the aluminum exposure models and the rest group was the control. After behavioral test, electrophysiological recordings were made at area CA1 from hippocampal SC branch followed by biochemical examination for several key kinases involved in LTP induction and formation. Results Chronic exposure of Al significantly decrease the activities of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) and reduced the expression levels of extracellular signal-regulated kinases (ERK1/2) and Ca 2+–calmodulin dependent protein kinase II (CaMKII) in hippocampus, attenuating the population spike (PS) amplitude of LTP from the hippocampal CA1 region, causing impaired memory abilities of rats. Conclusions Aluminum accumulation in the hippocampus affects several crucial kinases involved in LTP induction and formation, resulting in impairment of memory.

Aluminium-induced oxidative DNA damage recognition and cell-cycle disruption in different regions of rat brain

The present study was undertaken to reveal the effects of chronic aluminium exposure (10 mg/kg/b.wt, intragastrically for 12 weeks) on the oxidative DNA damage and its implication on the expression of p53 and other cell-cycle regulatory proteins in male Wister rats. Chronic aluminium exposure resulted in increased formation of 8-hydoxydeoxyguanosine in the mitochondrial DNA isolated from different regions of rat brain. The agarose gel electrophoresis revealed the DNA fragmentation pattern in aluminium-treated rat brain regions. Increased expression of p53 demonstrated that aluminium induces DNA damage. Western blot and mRNA expression analysis demonstrated increased expression of cyclin D1, suggesting disruption of cell cycle. The immunohistochemical studies showed nuclear localization of p53; however, the localization of cyclin D1 was both cytoplasmic and nuclear in aluminium-treated rat brain regions. Thus, the findings of the present study reveal that aluminium-induced oxidative damage to DNA may be involved in the neurodegeneration via increase in p53 expression and activation of cell cycle.

Effects of chronic aluminum exposure from prenatal to postnatal stage on Ng in hippocampus of young rats

Objective To study the change of LTP in hippocampus of young rats after chronic aluminum exposure of different concentration from prenatal to postnatal,and to go deep into the synaptic mechanism of that aluminum impairs learning and memory capacity.Methods The extracellular mieroelectrode technique was used to monitor the LTP.Results The occurrence of LTP in control group was 90.91%,in 0.2%-Al group was 58.33%,in 0.4%-Al group was 18.18%,compared with the control group,in 0.4%-Al group,the occurrence of LTP was remarkably decreased(P<0.01).The PS mean amplitudes relative to the baseline vAlues after HFS in control group was(144.09±18.43)%,in 0.2%.Al group Was (105.83±16.79)%,in 0.4%-Al group Was (91.00±18.98)%.compared with the control group,in the Al3+ exposed groups,the PS mean amplitudes relative to the haseline values were significanfly decreased(P<0.01),and the mean relative amplitude differences in relation to the baseline values at selected time periods after HFS were significantly decreased(P<0.01).Conclusion Aluminum exposure from prenatal to postnatal can damage the induction and maintenace of LTP in hippocampus of young rats.consquentely impair the ability of learning and memory. Key words: Aluminum exposure; Long-term potentiation; Period from prenatal to postnatal

Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage

Aluminium has been implicated in various neurodegenerative diseases but exact mechanism of action is still not known. Mitochondria being a major site of reactive oxygen species production are considered to be target of oxidative stress and it seems that the oxidative damage to mitochondrial proteins may underlie the pathogenesis of aluminium induced neurodegeneration. Thus, the present study was undertaken to reveal the effects of chronic aluminium exposure (10 mg/kg b.wt, intragastrically for 12 weeks) on the oxidative damage to mitochondrial proteins in male albino Wistar rats. Chronic aluminium exposure resulted in decrease in the activity of mitochondrial superoxide dismutase (MnSOD) and aconitase in different regions of rat brain suggesting increased oxidative stress. This decrease in MnSOD activity in turn might be responsible for the increased protein oxidation as observed in our study. All these processes taken together may cause increased oxidative damage to mitochondrial proteins in general. By taking the advantage of recent immunochemical probe for oxidatively modified proteins, we identified MnSOD to be susceptible to oxidative damage in aluminium treated animals. The quantitative RT-PCR analysis for Lon protease, a protease involved in the removal of oxidatively modified proteins from mitochondria, showed decreased mRNA expression suggesting increased oxidative damage and decreased removal of mitochondrial proteins. The identification of specific proteins as targets of oxidative damage may provide new therapeutic measures to reverse the effects of aluminium induced neurodegeneration.

Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium

The present study was designed with an aim to evaluate the effects of chronic aluminium exposure (10 mg/kg b.wt, intragastrically for 12 weeks) on mitochondrial energy metabolism in different regions of rat brain in vivo. Mitochondrial preparations from aluminium treated rats revealed significant decrease in the activity of various electron transport complexes viz. cytochrome oxidase, NADH cytochrome c reductase and succinic dehydrogenase as well, in the hippocampus region. The decrease in the activity of these respiratory complexes was also seen in the other two regions viz. corpus striatum and cerebral cortex, but to a lesser extent. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria isolated from aluminium treated rat brain regions. We also studied the spectral properties of the mitochondrial cytochromes viz. cyt a, cyt b, cyt c 1 , and cyt c in both control and treated rat brains. The various cytochrome levels were found to be decreased following 12 weeks of aluminium exposure. Further, these impairments in mitochondrial functions may also be responsible for the production of reactive oxygen species and impaired antioxidant defense system as observed in our study. The electron micrographs of neuronal cells depicted morphological changes in mitochondria as well as nucleus only from hippocampus and corpus striatum regions following 12 weeks exposure to aluminium. The present study thus highlights the significance of altered mitochondrial energy metabolism and increased ROS production as a result of chronic aluminium exposure in different regions of the rat brain.

Neurofilament phosphorylation and disruption: A possible mechanism of chronic aluminium toxicity in Wistar rats

The present study was designed to investigate the possible effects of chronic aluminium exposure on neurofilament phosphorylation and its subsequent disruption in various regions of the rat brain. An intra-gastric dose of aluminium (10 mg/kg bw for 12 weeks) resulted in a marked enhancement of Ca 2+/CaM dependent protein kinase activity as compared to cAMP dependent protein kinase. The levels of phosphoprotein phosphatase were found to be significantly depleted only in the cerebral cortex. After in vitro phosphorylation using [ 32γ-P] ATP, various proteins were resolved on one-dimensional 8% SDS-PAGE, stained with Coomassie Blue and autoradiographed. The amount of 32P-incorporated was quantified using ADOPE PHOTOSHOP (7.0). The 200 kDa neurofilament protein was identified using immunoblotting. Finally, the extent of phosphorylation induced neurofilamentous damage was assessed using immunocytochemical studies. The cytoskeletal proteins were found to be aggregated and disrupted in all the three neuronal regions following 12 weeks of aluminium treatment. This study lends further support to the possible role of aluminium as a potent neurotoxic agent and in the etiopathogenisis of various neurodegenerative diseases.

In vivo measurement of bone aluminium: Recent developments

A biomarker of aluminium accumulation in the human body can play a valuable role in determining health effects of chronic aluminium exposure, complementing other human and environmental monitoring data. In vivo neutron activation provides such a non-invasive biomarker. To date, the best in vivo neutron activation system used thermalised neutrons from a nuclear reactor at Brookhaven National Laboratory, which suffered only slightly from interference from other elements, primarily phosphorus, and from the disadvantage of restricted accessibility. At McMaster, we use a nuclear reaction on an accelerator to select neutron energy, which eliminates the interferences. Spectral decomposition analysis improved sensitivity. A new 4π detection system also enhanced sensitivity. Together these improvements yield a minimum detection limit of 0.24 mgAl in a hand, slightly better than at Brookhaven and equivalent to “normal” levels. Further improvements should result from a new irradiation cavity and from using a higher proton current on the accelerator to shorten irradiation times. The system is now ready for pilot human studies.

Disruption of Neuronal Calcium Homeostasis after Chronic Aluminium Toxicity in Rats

The present study was designed to investigate the possible effects of chronic aluminium exposure on the various aspects of calcium homeostasis in rat brain. Chronic aluminium administration caused significant rise in the intrasynaptosomal calcium levels. The activity of major calcium-expelling enzyme, i.e. Ca2+ ATPase was found to be lowered. Also, the calcium uptake via voltage-operated calcium channels increased significantly. Similar to the increase in intrasynaptosomal calcium, calpain activity was found to be increased. The results presented here, indicate that the toxic effects of aluminium could be mediated through modifications in the intracellular calcium homeostasis, which may lead to impaired neuronal function.

Effects of Chronic Aluminum Exposure on Swimming and Cardiac Performance in Rainbow Trout, Oncorhynchus mykiss

Rainbow trout were exposed to 0–80 μg l−1 aluminum (Al) at pH 5.2 in synthetic soft water, for up to 8 weeks. Trout were submitted to an incremental swimming test to quantify their aerobic swimming capacity (Ucrit). After a simple, non-invasive cardiac surgery to install Doppler flow probes, their heart rate, cardiac output and stroke volume were measured while swimming at increasing water velocities. Fish exposed to Al accumulated significant amounts of Al at the gills (0–80 μg g−1) and in their liver (5–60 μg g−1) and had decreases in swimming capacity, ranging from 11 to 21%. Analysis of cardiac parameters during swimming revealed that increases in heart rate were used in trout exposed to the highest concentrations of Al to increase cardiac output, whereas control fish tended to increase cardiac output through increases in stroke volume.

Regional alterations in calcium homeostasis in the primate brain following chronic aluminium exposure.

The present study investigates the possible effects of chronic aluminium exposure on the various aspects of calcium homeostasis in the primate central nervous system. Aluminium administration caused a marked decline in the activity of Ca2+ ATPase in the monkey brain. The total calcium content was also significantly raised following aluminium exposure. Concomittant to the increase in the calcium content, the levels of lipid peroxidation were also augmented in the aluminium treated animals, thereby further accentuating the aluminium induced neuronal damage. In addition, aluminium had an inhibitory effect on the depolarization induced 45Ca2+ uptake via the voltage operated channels. The results presented herein, indicate that the toxic effects of aluminium could be mediated through modifications in the intracellular calcium homeostasis with resultant altered neuronal function.