Cysteamine HCl Administration Impedes Motor and Olfactory Functions, Accompanied by a Reduced Number of Dopaminergic Neurons, in Experimental Mice: A Preclinical Mimetic Relevant to Parkinson's Disease

Brain Sci. 2024 Jun 24;14(7):632. doi: 10.3390/brainsci14070632.

Abstract

Cysteamine hydrochloride (Cys-HCl) has been established as a potent ulcerogenic agent of the gastrointestinal (GI) system. GI dysfunction and olfactory deficits are the most common clinical symptoms of many movement disorders, including Parkinson's disease (PD). Cys-HCl has been shown to interfere with dopamine, a neurotransmitter crucial for motor, olfactory, and cognitive functions. However, the reports on the effect of Cys-HCl treatment on the behavioral aspects and functions of the dopamine system appear to be inconsistent. Therefore, we revisited the impact of Cys-HCl on the motor function in experimental mice using a battery of behavioral tests, such as the pole test (PT), beam-walking test (BWT), and rotarod test (RDT), while the olfactory ability and cognitive functions were examined through the buried-food test (BFT) and Y-maze test. Furthermore, we investigated the effect of Cys-HCl on the number of dopaminergic tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) and olfactory bulb (OB) of the experimental mice using immunohistochemistry. The results revealed that Cys-HCl administration in the mice induced significant impairments in their motor balance and coordination, as their movement-related performances were markedly reduced in terms of the behavioral tasks. Mice exposed to Cys-HCl showed pronounced reductions in their odor discrimination abilities as well as cognitive impairments. Strikingly, the number of TH-positive neurons was found to be reduced in the SN and OB of the Cys-HCl-treated group, which is a bonafide neuropathogenic hallmark of PD. This study highlights the potential neurotoxic effects of Cys-HCl in experimental brains and suggests further investigation into its role in the pathogenesis of Parkinsonism.

Keywords: Parkinsonism; cysteamine HCl; motor coordination; olfaction; rotarod; tyrosine hydroxylase.

Grants and funding

M.K. has been supported by the University Grants Commission Faculty Recharge Programme (UGC-FRP), New Delhi, India. M.K. acknowledges RUSA 2.0 Biological Sciences, Bharathidasan University, the Anusandhan National Research Foundation (ANRF)/Science Engineering Research Board (SERB) (CRG/2023/005266), Government of India, for the financial support. The authors are grateful to UGC-SAP and DST-FIST for the infrastructure of the Department of Animal Science, Bharathidasan University. Divya Bharathi Selvaraj is the recipient of the RUSA 2.0 project fellowship (Ref. No. BDU/RUSA 2.0/TRP/BS/Date 22 April 2021). Jemi Feiona Vergil Andrews was supported as a project assistant from the project grant SERB EEQ/2016/000639.