Our observation in the present study emphasize that aluminium acetate has induced significant and varied levels of elevation in acetylcholine content and inhibition of acetylcholinesterase activity in all regions of rat brain under both modes of exposure. These observations substantiated that aluminium might be affecting various steps in the metabolic pathway of the neurotransmitters through end-product inhibition. ACh is synthesized in a single reaction from the precursors, acetyl CoA and choline, catalyzed by the enzyme choline acetyl transferase. Accumulation of ACh in various regions of rat brain in the present study under acute and chronic exposures to Al denote an increase in acetyl CoA.[12
] Similarly, decreased levels of AChE may be due to attachment of aluminium to the SH-groups of the enzyme at the active sites, thus preventing their functions in certain chemical reactions.[13
] Because the molecular weight of aluminium is less than 2000, it could pass through the blood-brain barrier easily and could affect the cholinergic system. The earlier research findings on zinc[14
] and lead toxicity[15
] in rats lend support to our present findings.
Historically, high levels of Al have not engendered concern because it appears that little of ingested aluminium is absorbed and what is absorbed is rapidly excreted. The absorption of aluminium is poorly understood that both soluble and mucosally associated aluminium metal binding ligands may regulate the initial uptake.[16
Aluminium toxicity has been recognized in many settings where exposure is heavy and prolonged and renal function is limited. In patients with osteomalacia, there has been a closely associated dialysis encephalopathy caused by aluminium deposition in brain.[2
] Because the elimination half-life of aluminium from the human brain is seven years, this can result in cumulative damage of the neurons by interfering with neurofilament axonal transport system, eventually leading to Alzheimer’s-like neurofibrillary tangles. The pathogenesis of aluminium toxicity is complex and may be related to other factors such as impaired parathyroid function and osteomalacia.[17
] Excess aluminium is known to exert direct effect on hematopoiesis, poor immunologic response, physical abnormalities such as stuttering, gait disturbance, myoclonic jerks, seizures, coma, abnormal EEG, and sudden death.
Variable levels of elevation in the cholinergic neurotransmitters and its associated enzymes in different brain regions of rat in the present study may be due to heterogeneous nature of the brain tissue and different roles assigned to them such as striatum-signs of toxicity, Cb-cognitive functions, Ht-body temperature, thirst emotions, Cb-equilibrium, Pm-respiratory disorders.[18
] Aluminium was known to accumulate in all regions of rat brain upon exposure to acute and subacute doses, maximum accumulation in Hc. Furthermore, aluminium was also seen to compartmentalize in almost all tissues of the body to varying extent, the spleen registering the highest levels.[19
] Canned soft drink fed rats had registered significantly higher blood, liver, bone aluminium concentration.[20
] The areas of rat brain exhibiting changes in cholinergic system are shown to exhibit the greatest changes in noncholinergic system,[21
] thus indicating their possible interdependence. Thus, it is conceived that the adaptive changes underlying tolerance to anticholinesterase agents also involve alterations in other neurotransmitter system in balance with the cholinergic system. Recovery tendency noticed in cholinergic system in all brain regions of intoxicated rat and its behavior further indicate the operation of the detoxification mechanisms and development of behavioral tolerance.
From our present observations, it was obvious that the fluctuations in the cholinergic system under aluminium toxicity coincided well with the frequency and magnitude of the signs and symptoms of several behavioral changes such as adipsia, aphagia, hypokinesia, etc. These observations further support that aluminium might have caused lesions in the important regions of brain like substantia nigra, Ht, etc. These motor deficits and motivational changes are closely associated with some of the symptoms characteristic to Parkinson’s disease.[22
] It has been reported that three patients who worked in aluminium smelting industry for 12 years were presented with severe asthma[23
] and a progressive neurological disorder viz. Potroom palsy with uncoordinated movements, tremors, cognitive deficits, etc.[24
] Furthermore, there is ample evidence that neurotoxic effects of aluminium in animals are directed at the central nervous system and long-term and low-level exposure to aluminium could explain the reasons for the Potroom palsy. These earlier reports on the aluminium toxicity to nervous system and finally culminating in development of neurodegenerative disorders[25
] in human beings altered its status from being a nontoxic, nonabsorbable, and harmless element to highly toxic heavy metal.
Regardless of the host and the route of administration, aluminium is proved as a potent neurotoxicant. In the young, adult, or developmentally matured host, the neuronal response to aluminium exposure can be dichotomized on morphological grounds, one involving intraneuronal neurofilamentous aggregation and the other producing significant neurochemical and neurophysiological perturbations such as speech disturbances and abnormal EEG, progressive encephalopathy with muscular atrophy, reduced mental development index, etc.[26
] Aluminium toxicity is a wide-spread problem in all forms of life including human beings, animals, fishes, plants, and trees and causes wide spread degradation of environment and death. Even though aluminium is not considered to be a heavy metal like lead, it can be toxic in excessive amounts and even in small amount, if deposited in brain.
All our observations in the present study provide conclusive evidences that the aspect of aluminium toxicity to human beings needs special attention from the environmentalist point of view because it might increase the risk of occupational hazards with particular reference to neurological diseases.