Patricio-Martinez_2026_Neurosci__

The recombinant C-terminal domain of tetanus toxin (Hc-TeTx) has been reported to exert neurotrophic-like effects in experimental models of neurodegeneration, potentially through activation of signaling pathways associated with tropomyosin receptor kinase A (TrkA). However, its effects on basal forebrain cholinergic dysfunction induced by amyloid-beta remain incompletely characterized. The present study evaluated whether administration of Hc-TeTx in the nucleus basalis magnocellularis (NBM) is associated with attenuation of Amyloid beta peptide 25-35 (Abeta((25-35)))-induced alterations in cognitive function, cholinergic markers, and related signaling pathways. Adult rats received bilateral intracranial injections of Hc-TeTx (50 ng per hemisphere) followed by Abeta((25-35)) (1 microg per hemisphere) into the NBM. Spatial learning and memory were assessed using the eight-arm radial maze. Biochemical analyses included acetylcholinesterase (AChE) activity, vesicular acetylcholine transporter (VAChT) expression, and phosphorylation of TrkA, Akt, and GSK-3beta. Astrocytic reactivity was evaluated by GFAP immunoreactivity in the NBM, frontal cortex, and temporal cortex. Abeta((25-35)) administration impaired spatial learning and memory, reduced AChE activity and VAChT expression, altered TrkA/Akt/GSK-3beta signaling, and increased GFAP immunoreactivity. In contrast, Hc-TeTx treatment was associated with improved behavioral performance, preservation of cholinergic markers, modulation of TrkA-related signaling, and reduced astrocytic reactivity. These findings indicate that Hc-TeTx administration in the NBM is associated with attenuation of Abeta((25-35))-induced cholinergic dysfunction and related molecular alterations. However, the underlying mechanisms remain to be fully established, and the present results should be interpreted as associative rather than demonstrating a direct causal role of TrkA signaling.