Effect of Alpha Lipoic Acid on Degenerative Alterations in the Primary Culture of Mouse Cerebrocortical Neurons

Objective: Neurons are non-dividing cells that accumulate damaged biomolecules over time. Cytological hallmarks of neurodegeneration include the formation of neurofibrillary tangles in the axon, deposition of extracellular amyloid beta plaques and accumulation of lipofuscin granules in the cyton. These deposits impair neuronal function by disrupting synaptic transmission, axonal transport and intracellular waste recycling. In addition, there is a loss of Nissl substance. It consists of ribonucleoprotein particles essential for neuronal protein synthesis. Alpha lipoic acid (ALA) is routinely prescribed by neurophysicians and orthopaedic surgeons in the treatment of nerve compression, neurodegenerative diseases, etc. very effectively. However, no reports are available on the effect of ALA on cellular degenerative alterations in the neurons. Material and methods: This study aimed to assess ALA’s potential in mitigating cellular neurodegenerative alterations. For this purpose, the cerebrocortical neurons from E17 mouse embryos were cultured on poly-l-lysine-coated coverslips and maintained in neurobasal medium supplemented with B-27 supplement at 37°C in 5% CO2 until the completion of the experiments. Two-thirds of the medium was replaced by fresh medium on every third day. Neurons were divided into the control and the experimental group. The latter was treated with ALA (100 µM) up to the 7th day of culture. On the eighth day, neurofibrillary tangles, amyloid beta, lipofuscin granules and Nissl substance were studied using cytochemical staining procedures and levels of malondialdehyde were biochemically quantified. Results: The treatment of ALA (100 µM) for 7 days resulted in highly significant reduction in neurofibrillary tangles, β-amyloid plaques, and lipofuscin granules as compared to the control group. Moreover, the Nissl substance was significantly preserved in ALA-treated neurons (p < 0.001). In addition, there was significant decline in the levels of Malondialdehyde (p < 0.001). Conclusion: ALA confers neuroprotective effects in primary culture of mouse cerebrocortical neurons by attenuating degenerative alterations and decreasing the oxidative damage to membrane phospholipids. These findings unravel the role of Alpha lipoic acid in conferring neuroprotection by decreasing the cytological degenerative alterations.