We reduced glutathione levels, and Catalase and superoxide

            We
found that, AlCl3 supplementation will lead to severe memory deficits in Rats.
Followed by PCA treatment, showed an improvement in these symptoms. AlCl3     found in our daily life as in drinking water,
soil and tooth paste, moreover, it is used to manufacture cooking utensils 35.
It leads to oxidative deterioration of cellular lipids, proteins and DNA36.
Lipid peroxidation can cause tissue damage under chronic condition37-38
therefore, Aluminium can be considered as a contributing factor in AD. After
chronic exposure, aluminium accumulates in all brain regions with greater
accumulation in cortex and hippocampus39-41. Hippocampus and frontal
cortex play an important role in learning and memory42, which is
severely affected in neurodegenerative disorders such as AD and Parkinson
disease (PD). It is a potent cholinotoxin and causes apoptotic neuronal loss,
which is a characteristic symptom of neurodegeneration associated with AD 47.
Chronic administration of aluminium chloride results in progressive
deterioration of spatial memory in Morris’s water maze task paradigms. It leads
to impairment of glutamate-NO-cGMP pathway to the cerebellum of rats48.

            In
our study, we observed marked oxidative stress as indicated by an increase in
lipid peroxidation, nitrite levels, decrease in reduced glutathione levels, and
Catalase and superoxide dismutase activity in animals by chronic administration
of aluminium chloride. This could be due to the reduced axonal mitochondria
turnover, disruption of Golgi and reduction of synaptic vesicles induced by
aluminium treatment, which results in release of oxidative products like
malondialdehyde TBARS, carbonyls, peroxynitrites and enzymes like superoxide
dismutase within the neurons51.

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            Impaired
cholinergic transmission is one of the complications seen in the
etiopathogenesis of memory deficit in AD. The neurodegeneration in frontal
cortex and hippocampus areas within the brain53 resulting in
impaired cholinergic transmission by two ways. Firstly, in AD patients, it
occurs either due to (I) decline in Ach release (ii) decreased choline
acetyltransferase activity (ChAT), which results in the scarcity of
Acetylcholine 54-55. Secondly, elevated acetyl cholinesterase (AchE)
enzyme further adds to scarcity of Ach at the synapse by degrading the
available Ach52. This degradation of Ach is abolished by PCA (AchE
inhibitor) so it’s effective in AD through improvement in cholinergic
transmission.

            PCA
(Hydroxycinnamic acid) belongs to phenolic acids with bioactive carboxylic
acids; this class mainly includes caffeic acid, ferulic acid, and PCA 56,
57. It is a frequent phytochemical in the human diet. It’s a potent
inhibitor of an enzyme AchE 58, 59. This could be a possible
mechanism by it inhibits cerebral hypoxia and improved memory disturbance by activating
cholinergic functionAcetylcholine (Ach) and choline acetyltransferase (ChAT)60.

            Chronic
aluminium exposures have been reported to result in cognitive58 and
locomotor impairment 59. The cognitive deficit is evident to
declined performance in Morris water maze test 60 and radial arm
maze test 61. In our study, aluminium treatment resulted in
behavioral changes such as a spatial memory deficit, indicated by increased
escape latency and decreased in time spent in target quadrant NW. Selegiline
and PCA antagonized the spatial memory deficit caused by aluminium. This
suggests the neuro protective role of PCA in correcting cognitive dysfunction
associated with aluminium exposure.

            Assessment
of locomotor activity is a requirement for evaluating any possible CNS
depressant/stimulant effect of interventions on animals. Similar to previous reports
60, a decline in locomotor activity in aluminium treated rats was
observed, indicating the CNS depressant effect of chronic aluminium exposure.
Treatment with Selegiline and PCA corrected the locomotor in-coordination
caused by aluminium chloride.

            MAO
inhibitors are unique in that they exert their protective effect on both
vascular and neuronal tissue by increasing Nitric oxide (NO) production in
brain tissues and cerebral blood vessels. Which is evidentially observed less
in AD brain 61. So this study also indicates that PCA may play a
significant role as MAO inhibitor and increasing NO release in brain tissues.

            Histopathological
examination of Aluminium chloride induced AD brain showed spongy cell, neuronal
necrosis. Cells degenerated with small nuclei leading to eosinophilic deposition. However, besides these
pathological hallmarks, AD brain exhibited a clear evidence of chronic inflammation
and oxidative damage 60-64. These are also thought to play a
significant role at the onset and progression of AD. Present study also
supports an evidence of inflammation with high concentration of TNF? in brain
tissues as compared with control rats. Administration of Selegiline and PCA in
AD rats improved the pathogenesis of AD as demonstrated by an improvement in
the behavioral (levels of activity and motor coordination), Inflammatory
(TNF-?) and biochemical parameters in the brains, which was further confirmed
by an improvement in brain tissue characteristics on histopathological
analysis.

            Accumulation
of free radicals may cause degenerative events of aging such as AD and because PCA
showed its potential against this neurotoxic (AlCl3) agent so it should be used
in treatment of dementia or AD (Fig. 3).

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