Quantitative study of aluminum‐induced changes in synaptic ultrastructure in rats

Abstract

Some evidence suggests that aluminum is one of the risk factors in Alzheimer's disease (AD); however, there is no study on the relationship between the synaptic configuration changes and aluminum uptake. In the present study, 40 rats were fed with water solution aluminum for 3 months and the effects of aluminum on the Gray's type I synapses in hippocampus and frontal cortex of rats were quantitatively investigated by electron microscopy. The effects of aluminum on the ability to learn and memorize were tested by a Morris water maze. Length of synaptic active zone, width of synaptic cleft, curvature of synapse, and thickness of postsynaptic density (PSD) were measured in the interface of synapses by the IBM-PC microimage processing system. The flat synapse, positive and negative curvature synapses, as well as the perforated synapse were classified and counted according to the type of the interfacial structure of a synapse. The amounts of aluminum deposited in brain were measured with an atomic absorption spectrophotometer. Our results show that the time and the distance taken by the rats to find the water maze increased after the rats were fed aluminum for 3 months. As compared with control, the synapses in aluminum-induced rats exhibited the following significant changes: decreased thickness of PSD (P < 0.01), increased width of synaptic cleft (P < 0.05), increased numbers of flat synapse, decreased numbers of positive curvature synapse and perforated synapse, and significantly increased aluminum deposits in hippocampus and frontal cortex (P < 0.01). Our study indicates that aluminum can decrease the ability of rats to learn and memorize and induce their synaptic configuration changes. These changes may be related to synaptic efficacy and may be one of the mechanisms for AL to induce AD.

Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats

“…A decrease trend of body weight was observed in Alexposed rats, especially in 0.6% AlCl 3 group (no decrement of food intake) comparing with that of the control rats, which was consistent with previous reports (Hermenegildo et al, 1999;Jing et al, 2004). Meanwhile, it was shown that hippocampus, brain coefficients and hippocampus/ brain ratio in Al-exposed rats reduced gradually with the increase of Al doses.…”

“…It was reported that Al deposited in the brain could impair the configuration of synapse, postsynaptic membrane and PSD which reflected the synaptic organization and metabolism (Jing, 2004). Especially, the thickness of the PSD represented synaptic efficacy (Jing, 2004); synaptic curvature reflected a morphological index of synaptic plasticity representing the different function of synapses such as the neuron transmitter release signs and the configuration changes in postsynaptic receptors (Markus and Petit, 1989). Subtle changes in synaptic structure can alter biophysical properties of synapses (Tang et al, 2001).…”

“…In addition, another research revealed that synaptic plasticity referred to the change of synaptic efficacy, the changes of synaptic transmission efficacy are usually followed by the structural modification of synapses (Lu, 2008). Jing has reported that aluminum decreases the thickness of post-synaptic density, increase the width of the synaptic cleft, and increase the number of flat synapses (Jing, 2004). In this study, it was shown that there were more shrunk cells with condensed cytoplasm, swollen mitochondria, increased heterochromatin, vacuolated organelles and even lost in neurons, there were fewer synaptic vesicles, thinner PSD, shorter active synaptic zone, and uneven synaptic curvature in synapses, and there were thinner pyramidal cell layer, irregular arrangement and vacuolar degeneration observed with HE staining in hippocampus CA1 and CA3 area after AlCl 3 exposure (Fig.…”

Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain

“…In this study, we demonstrate that AlCl 3 induces toxic fibrillar Aβ aggregation in cortex and hippocampus of mice brain. Moreover documented reports denote that aluminium was specifically deposited in cortex and hippocampal regions of AD patients and also in rodents exposed to aluminium [33,34,35]. These reports support documented report denotes that Amyloid-β 42 induces neuronal cell death via ASK-1 [36] and JNK activation [37].…”

Does neurotransmission impairment accompany aluminium neurotoxicity?

“…In recent studies, aluminium-induced degradation in the ability to learn and memorize was linked to the configurational changes in synapse [250,251]. The observed abnormal synaptic ultrastructure was characterized by a reduction in the thickness of postsynaptic density, enlargement of synaptic cleft and attenuation of synaptic curvature (Table 9).…”