Mechanism of SIRT1 in Regulating Learning and Memory via Modulating Neurotransmitter Metabolic Homeostasis

doi:10.19586/j.2095-2341.2025.0154

Current Biotechnology ›› 2026, Vol. 16 ›› Issue (2): 395-411.DOI: 10.19586/j.2095-2341.2025.0154

• Articles • Previous Articles

Mechanism of SIRT1 in Regulating Learning and Memory via Modulating Neurotransmitter Metabolic Homeostasis

Yanan QIAO¹(), Yubing ZENG¹(), Xuejia HE¹^,², Fan LIU¹, Shan WANG¹()

^1.Capital Medical University Affiliated Capital Children's Medical Center，Capital Institute of Pediatrics，Beijing 100020，China
^2.Pediatrics Department，Provincial Hospital Affiliated to Shandong First Medical University，Jinan 250021，China

Received:2025-11-06 Accepted:2025-12-25 Online:2026-03-25 Published:2026-04-27
Contact: Shan WANG

Abstract

Abstract:

SIRT1， an NAD⁺-dependent deacetylase， plays a pivotal role in maintaining neuronal function and metabolic homeostasis. However， its molecular mechanisms in regulating neurotransmitter metabolism and cognitive impairment remain unclear. In this study， we established a Sirt1-deficient mouse model （Sirt1^+/- ） and performed transcriptomic and metabolomic analyses on hippocampus to systematically investigate the impact of SIRT1 loss on cerebral neurotransmitter metabolic networks and cognitive function. Phenotypic observations revealed that Sirt1^+/- mice exhibited significant deficits in spatial memory and learning abilities. Metabolomic and transcriptomic profiling demonstrated that SIRT1 deficiency led to metabolic dysregulation of key neurotransmitters， including glutamate and γ-aminobutyric acid （GABA） in the hippocampus， accompanied by marked upregulation of neurotransmitter metabolism-related genes like Gad1 and Gad2. Integrated multi-omics analysis further confirmed that SIRT1 deficiency suppressed neuroactive ligand-receptor interactions and cAMP signaling pathways， resulting in disrupted neurotransmitter homeostasis and subsequent cognitive dysfunction. In conclusion， this study elucidates a novel mechanism by which SIRT1 maintains cognitive function through coordinated reprogramming of neurotransmitter metabolism and energy homeostasis， providing potential therapeutic targets for neurodegenerative disorders.

Key words: SIRT1, neurotransmitter metabolic homeostasis, glutamate, gamma-aminobutyric acid, learning and memory dysfunction

CLC Number:

Q756

Yanan QIAO, Yubing ZENG, Xuejia HE, Fan LIU, Shan WANG. Mechanism of SIRT1 in Regulating Learning and Memory via Modulating Neurotransmitter Metabolic Homeostasis[J]. Current Biotechnology, 2026, 16(2): 395-411.

Figures/Tables 8

Table 1 Primers used in this study

基因名称	上游引物（5′→3′）	下游引物（5′→3′）
Gad1	5′-AACGTATGATACTTGGTGTGGC-3′	5′-CCAGGCTATTGGTCCTTTGTAAG-3′
Gad2	5′-TCCGGCTTTTGGTCCTTCG-3′	5′-ATGCCGCCCGTGAACTTTT-3′
Gabra2	5′-AGTCAGTGGCCCATAACATGA-3′	5′-TTGTGTAAGCGTAGCTTCCAAA-3′
Trpv1	5′-CCGGCTTTTTGGGAAGGGT-3′	5′-GAGACAGGTAGGTCCATCCAC-3′
Trpv4	5′-ATGGCAGATCCTGGTGATGG-3′	5′-GGAACTTCATACGCAGGTTTGG-3′

Fig. 1 SIRT1 deficiency impairs learning and memory abilities

Fig. 2 DEGs in the hippocampus of Sirt1+/- mice are closely related to synaptic signal transduction in neurons

Fig. 3 The loss of SIRT1 inhibits neurotransmitter synaptic signaling

Fig. 4 SIRT1 deficiency triggers extensive reprogramming of the hippocampal metabolome

Fig. 5 The absence of SIRT1 disrupts the metabolic homeostasis of key neurotransmitters in the hippocampus

Fig. 6 Multi-omics analysis reveals the impact of SIRT1 deficiency on pathways related to neurotransmitter metabolism

Fig. 7 SIRT1 plays a pivotal role in regulating neurotransmitter metabolism and preserving cognitive function

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Mechanism of SIRT1 in Regulating Learning and Memory via Modulating Neurotransmitter Metabolic Homeostasis

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