ROLES OF CHOLINERGIC SYSTEM IN COGNITIVE DYSFUNCTION

Pan Meng Liy, Dr Ebenezer Chitra and Dr. Sarmishtha Ghosh*

ABSTRACT

Acetylcholine (ACh) neurotransmitter plays a role in cortical development, adult neurogenesis, spatial learning, attention, memory, and cognition. Impairment of cholinergic system can contribute to the neurodegenerative diseases in old ages such as Alzheimer’s and Parkinson’s. Alzheimer’s is mainly caused by the accumulation of amyloid plaques produced from proteolysis of APP. APP interacts with α7nAChRs causes hyperphosphorylation of tau proteins and eventually destruction of neurons. Plus, ACh modulates the activity of MSNs to release dopamine. Loss of dopamine in Parkinson’s elevates the firing rate of basal ganglia neurons and affects the motor coordination. Additionally, cognitive dysfunction can occur at any age, and in diseases such as schizophrenia and depression. Depletion of mAChRs, which are responsible to control GABA release in schizophrenia causes imbalance between inhibition and excitation of neural circuit. Lastly, depression can be caused by neuroinflammation which involves α7 nAChRs that are responsible for regulating anti- inflammatory pathway; elevated cholinergic tone could also lead to depression.

Keywords: Acetylcholine; neurodegenerative diseases; alzheimer’s; parkinson’s; schizophrenia; depression.