Therapeutic Potential of Agmatine in Essential Tremor Through Regulation of Lingo-1 and Inflammatory Pathways

Purpose: Essential tremor (ET) is a prevalent movement disorder, yet current therapeutic options remain limited. Emerging evidence implicates leucine-rich repeat and immunoglobulin-like domain-containing protein (Lingo-1) and neuroinflammation in the pathophysiology of ET. This study aimed to investigate whether agmatine, a biogenic amine neuromodulator attenuates tremors and modulates the expression of Lingo-1 and proinflammatory markers in a rodent model of ET.

Methods: Tremor was induced in male Swiss Webster mice through intraperitoneal injections of harmaline (10 mg/kg) on Days 1, 3, and 5 of the study. During the same period, agmatine (40 mg/kg) was administered for 5 consecutive days. Behavioral assessments of tremor severity, gait, balance, muscular strength, locomotion, anxiety-like behavior, and memory were conducted. Moreover, Lingo-1 and interleukin (IL)-6 gene expression was examined in the cerebellum using real-time polymerase chain reaction (RT-PCR).

Findings: Our findings demonstrated that agmatine administration significantly reduced tremors, ameliorated anxiety-like behaviors, and attenuated harmaline-induced locomotor deficits. At the molecular level, agmatine treatment significantly suppressed the overexpression of Lingo-1 elicited by harmaline. Moreover, IL-6 expression was attenuated to an extent comparable to control levels.

Conclusions: Collectively, this study provides the first evidence that agmatine dampens tremor severity, improves behavioral outcomes, and modulates key pathways implicated in ET pathogenesis in a rodent model. The ability of agmatine to normalize Lingo-1 and IL-6 expression suggests regulation of these pathways could underlie its neuroprotective action. These results suggest promise for agmatine as a prospective therapeutic agent in ET.