Listeria monocytogenes invasion in goat brain tissues: mechanisms of blood–brain barrier disruption and regulation of apoptosis and autophagy

Background: (LM), a zoonotic intracellular pathogen, causes fatal neurological infections in ruminants (e.g., goats) and humans. However, the mechanisms by which LM breaches the blood-brain barrier (BBB) and regulates neuronal programmed cell death (apoptosis/autophagy) remain unclear in caprine models-knowledge that is critical for livestock disease control. This study aimed to investigate the spatiotemporal invasion pathway of LM in goat central nervous system, its brain region-specific effects on apoptosis and autophagy, and the role of the Pink1/Parkin pathway in mitochondrial autophagy during LM infection. Methods: Goats were intravenously infected with LM to establish an intracranial infection model. Bacterial loads in brain tissues were quantified, and multiple techniques (immunofluorescence, TUNEL, immunohistochemistry, Western blot, qRT-PCR) were used to detect BBB integrity, apoptotic/autophagic markers, and related pathway proteins (E-cadherin/c-Met, Bcl-2/Bax, LC3B, Pink1/Parkin). Results: LM showed tropism for brainstem regions (midbrain, pons, medulla oblongata) with focal colonization in neurons and glial cells. BBB tight junction proteins (ZO-1, Claudin-1, Occludin) exhibited region-specific dysregulation; notably, an upregulation of Claudin-1 and Occludin was observed in the medulla, suggesting a localized compensatory response. LM infection was associated with the activation of the E-cadherin/c-Met pathway, potentially facilitating transendothelial and neuronal invasion. Apoptosis (Bcl-2/Bax imbalance) and autophagy (LC3B, Pink1/Parkin) were heterogeneously regulated across brain regions, with significant quantitative changes observed in the cerebrum, cerebellum, midbrain, and medulla. Conclusion: LM invades goat brain tissues coinciding with BBB disruption, exhibits brainstem tropism, and modulates apoptosis and autophagy through region-specific pathways, providing novel insights into LM-induced neurological pathogenesis in ruminants.