Lauric acid (LA), a saturated medium-chain fatty acid found in coconut oil, palm kernel oil, and breast milk, is known for its antimicrobial and neuroprotective properties. While manganese (Mn) is vital in small quantities, excessive accumulation in the human body can be harmful, causing neurological and other health complications. This study evaluated the dose-dependent neuroprotective effects of LA against hippocampal neurotoxicity and Alzheimer's disease (AD)-like features induced by Mn exposure in juvenile mice.

Juvenile mice (N = 35, ≈6 weeks old, 20–22 g) were randomly assigned to five groups (n = 7): control (double-distilled water), Mn-only (100 mg/kg), and three Mn + LA groups (125, 250, and 500 mg/kg LA). Treatments were administered orally for 8 weeks.

Mn exposure significantly (p < 0.05) impaired all behavioural parameters, significantly (p < 0.05) elevated malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and glutamate, and significantly (p < 0.05) reduced superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), interleukin-10 (IL-10), brain derived neurotrophic factor (BDNF), and acetylcholine (ACh). LA treatment, particularly at higher doses, significantly (p < 0.05) reversed these alterations. Histological analysis revealed neurodegenerative changes in the Mn-only group, including pyknotic nuclei, vacuolations, and neuritic pathology. LA significantly (p < 0.05) mitigated these alterations. Increased pro-inflammatory cytokines and caspase-3 activity in Mn-exposed groups was also significantly (p < 0.05) attenuated by LA treatment. Behavioral tests showed cognitive impairments in Mn-exposed mice, which were significantly (p < 0.05) improved by LA treatment.

LA demonstrates significant neuroprotective effects against Mn-induced hippocampal damage, likely through its antioxidant, anti-inflammatory, and anti-apoptotic actions, supporting its potential as a therapeutic agent for neurotoxicity and neurodegenerative conditions.