Trigonelline Ameliorates Learning and Memory and Synaptic Plasticity Impairment in Intrahippocampal Amyloid Beta (1-40) Rat Model of Alzheimer’s Disease

Intrahippocampal amyloid β (Aβ) negatively affects synaptic plasticity with subsequent impairment of learning and memory. Trigonelline is an alkaloid commonly found in fenugreek seeds and coffee beans with neuroprotective property and a promising agent for management of neurodegenerative disorders like Alzheimer’s disease (AD). In the present study, the possible beneficial effect of trigonelline on the improvement of learning and memory and synaptic plasticity was evaluated in Aβ (1-40) rat model of AD. For modeling AD, aggregated A𝛽 (1-40) (10 𝜇g/2 𝜇l for each side) was bilaterally microinjected into the hippocampal CA1 area. Trigonelline was administered p.o. at a dose of 100 mg/kg. The results showed that trigonelline pretreatment of Aβ-microinjected rats ameliorates learning and memory deficit in passive avoidance task and spatial memory impairment in Morris water maze (MWM) paradigm. It also improved population spike (PS) amplitude and field excitatory post-synaptic potential (fEPSP) slope following application of high frequency stimulation (HFS) to induce long-term potentiation (LTP) in medial perforant-dentate gyrus pathway as an index of synaptic plasticity. Additionally, trigonelline mitigated hippocampal activity of acetylcholinesterase (AChE). In summary, trigonelline pretreatment of intrahippocampal Aβ-microinjected rats could ameliorate learning and memory impairment, partly through restoring hippocampal synaptic plasticity and AChE and it may be suggested as an adjunct and promising oral bioactive therapeutic agent that may prevent memory deterioration in AD.