VULNERABILITY OF NEUROPEPTIDE Y–EXPRESSING INTERNEURONS IN ADULTHOOD FOLLOWING NEONATAL MONOSODIUM GLUTAMATE–INDUCED EXCITOTOXICITY

Excitotoxicity, resulting from excessive glutamatergic stimulation, is a primary mechanism of neuronal damage within the central nervous system. Neuropeptide Y (NPY), a 36–amino acid neuropeptide, acts as a key endogenous modulator with anticonvulsant effects, particularly within the hippocampal region. Interneurons expressing this peptide (NPY⁺ INs) play an essential role in regulating excitability in the dentate gyrus; however, they may be especially vulnerable to early-life brain insults.
The study aimed to investigate the role of NPY in modulating excitotoxic damage and to analyze the long-term impact of neonatal excitotoxicity on these specific interneuron populations in adulthood. An experimental model of early-life excitotoxicity was established using male rats treated with monosodium glutamate (MSG; 4 g/kg, administered subcutaneously) on postnatal days 1, 3, 5, and 7. At 60 days of age (adulthood), IN-NPY⁺ interneuron counts (cells/µm²) were obtained in the hilus of the dentate gyrus by immunohistochemistry for NPY protein, comparing MSG-treated (n = 4) and control (n = 4) groups. Quantitative analysis revealed a significant reduction in NPY⁺ IN density in the hilus animals exposed to MSG during the neonatal period compared to control group. The results indicate that neonatal excitotoxic insults result in a persistent alteration of inhibitory mechanisms in the hippocampus. The loss of IN-NPY⁺ interneurons represents a vulnerability factor for the control of neuronal excitability, linking early-life seizures and damage to long-term neurological dysfunction. Reduced of IN-NPY⁺ increases neuronal excitability and may contribute to an increase of seizure susceptibility in adulthood following neonatal excitotoxic and seizure damage.