Summary: Trigonelline (TG), a naturally occurring alkaloid present in coffee, fenugreek seed, and radish, shows promise for reducing age-related cognitive decline. In a controlled study using an accelerated-aging mouse model, oral TG improved spatial learning and memory and altered hippocampal biology in ways consistent with reduced neuroinflammation and enhanced neurotransmitter signaling.
Researchers from the University of Tsukuba administered TG to senescence-accelerated mouse prone 8 (SAMP8) animals and evaluated both behavior and molecular changes in the hippocampus. Behavioral testing and whole-genome transcriptomic and biochemical analyses together reveal mechanisms by which TG may protect against or reverse aspects of age-associated memory impairment.
Key Facts:
- Trigonelline (TG), found naturally in coffee, fenugreek seed, and radish, produced measurable improvements in spatial learning and memory in aged SAMP8 mice.
- Whole-genome hippocampal transcriptomics indicate TG influences pathways for nervous system development, mitochondrial function, ATP synthesis, and neurotransmitter release, while also engaging processes related to autophagy.
- TG reduced markers of neuroinflammation by impacting Traf6-mediated NF-κB signaling and lowered proinflammatory cytokines (TNF-α and IL-6) while increasing hippocampal levels of dopamine, noradrenaline, and serotonin.
Source: University of Tsukuba
Background: Identifying safe, functional natural compounds that can slow or reverse cognitive decline is a growing priority for promoting healthy aging. Trigonelline (TG) has attracted attention because it is abundant in common dietary sources such as coffee and certain vegetables and has previously been associated with neuroprotective properties.
In the reported study, 16-week-old SAMP8 mice received daily oral doses of TG (5 mg/kg) for 30 days. Cognitive performance was evaluated using the Morris water maze, a well-established test of spatial learning and memory. TG-treated mice demonstrated significant improvements in escape latency, swimming distance, and annulus crossing index compared with untreated SAMP8 controls, indicating better acquisition and recall of spatial information.
To probe mechanisms, investigators performed whole-genome transcriptomic profiling of hippocampal tissue. Gene ontology and pathway analyses revealed enrichment in biological processes linked to nervous system development, mitochondrial function and ATP synthesis, inflammatory signaling, autophagy, and neurotransmitter release. Dimensionality reduction methods (UMAP) highlighted that modulation of inflammatory pathways was a primary effect of TG, followed closely by changes in neurotransmitter-related pathways.
Additional network analysis suggested TG may act by negatively regulating Traf6-driven activation of NF-κB, a central transcriptional regulator of inflammation. Consistent with this, quantitative protein assays (ELISA) showed significant reductions in proinflammatory cytokines TNF-α and IL-6 in the hippocampus of TG-treated mice. Parallel biochemical measurements found elevated levels of the neurotransmitters dopamine, noradrenaline, and serotonin, which support synaptic function and cognitive processes.
Taken together, the behavioral, transcriptomic, and biochemical data provide convergent evidence that TG can both suppress neuroinflammation and enhance neurotransmitter systems in the aging hippocampus, coinciding with improved spatial learning and memory performance in a senescence-accelerated mouse model. These results support further exploration of TG as a dietary or therapeutic candidate to mitigate age-related cognitive impairment.
Funding: This research was supported by DyDo DRINCO and the Japan Science and Technology Agency (JST grant number JPMJPF2017).
About this memory research news
Author: YAMASHINA Naoko
Source: University of Tsukuba
Contact: YAMASHINA Naoko – University of Tsukuba
Image: The image is credited to Neuroscience News
Original Research: Open access. “Transcriptomics and Biochemical Evidence of Trigonelline Ameliorating Learning and Memory Decline in the Senescence-Accelerated Mouse Prone 8 (SAMP8) Model by Suppressing Proinflammatory Cytokines and Elevating Neurotransmitter Release” by KAGAWA, Tamami et al., published in GeroScience.
Abstract
Transcriptomics and Biochemical Evidence of Trigonelline Ameliorating Learning and Memory Decline in the Senescence-Accelerated Mouse Prone 8 (SAMP8) Model by Suppressing Proinflammatory Cytokines and Elevating Neurotransmitter Release
This study addresses the need for natural compounds that can mitigate aging-associated cognitive decline. Using an integrated cognitive and molecular approach, researchers examined the effects of trigonelline on memory and spatial learning in 16-week-old SAMP8 mice. After 30 days of daily oral administration of TG at 5 mg/kg, mice underwent Morris water maze testing and showed significant behavioral improvements in standard measures of spatial learning and memory.
Comprehensive whole-genome transcriptome profiling of hippocampal tissue revealed that TG treatment enriched multiple biological processes and pathways, including nervous system development, mitochondrial function and ATP production, inflammation, autophagy, and neurotransmitter release. Clustering and network analyses pointed to negative modulation of Traf6-mediated NF-κB activation as a likely mechanism for TG’s anti-inflammatory effects. Finally, biochemical assays confirmed reductions in proinflammatory cytokines (TNF-α and IL-6) and increases in key neurotransmitters (dopamine, noradrenaline, and serotonin), supporting the compound’s role in protecting hippocampal function and improving age-related cognitive deficits.