Dataset Information

IDA-SWATH proteomic analysis of rat hippocampus upon methylglyoxal treatment

ABSTRACT: Diabetes is one of the major risk factors for Alzheimer’s disease (AD) development. The role of elevated levels of glucose, methylglyoxal (MGO), and advanced glycation end products (AGEs) in diabetes in the pathogenesis of the AD is not well understood. In this pursuit, we studied the role of methylglyoxal in the pathogenesis of AD in rat models. The elevated plus-maze (EPM) behavioural study indicated that MGO induces anxiety. Treatment of telmisartan (RAGE expression inhibitor) and aminoguanidine (MGO quencher) attenuated MGO induced anxiety. Further, hippocampal proteomics demonstrated that MGO treated rats differentially regulate proteins involved in calcium homeostasis, mitochondrial functioning, and apoptosis which may affect neurotransmission and neuronal plasticity. Hippocampal tau phosphorylation level was increased in MGO treated rats which was reduced in presence in aminoguanidine and telmisartan. Plasma fructosamine level was increased upon MGO treatment. Hippocampal histochemistry showed vascular degeneration and neuronal loss upon MGO treatment. This study provides mechanistic insight into the role of MGO in the diabetes-associated development of AD.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Gouri Patil

LAB HEAD: Mahesh Kulkarni

PROVIDER: PXD037673 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Behavioral and Proteomic Studies Reveal Methylglyoxal Activate Pathways Associated with Alzheimer's Disease.

Patil Gouri G Kulsange Shabda S Kazi Rubina R Chirmade Tejas T Kale Vaikhari V Mote Chandrashekhar C Aswar Manoj M Koratkar Santosh S Agawane Sachin S Kulkarni Mahesh M

ACS pharmacology & translational science 20221227 1

Diabetes is one of the major risk factors for Alzheimer's disease (AD) development. The role of elevated levels of glucose, methylglyoxal (MGO), and advanced glycation end products (AGEs) in the pathogenesis of AD is not well understood. In this pursuit, we studied the role of methylglyoxal in the pathogenesis of AD in rat models. The elevated plus-maze (EPM) behavioral study indicated that MGO induces anxiety. Treatment of telmisartan (RAGE expression inhibitor) and aminoguanidine (MGO quencher ...[more]

PMID: 36654748

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Project description:Background: While stressful events are recognized as an important cause of major depressive disorder (MDD), some individuals exposed to life stressors maintain normal psychological functioning. Although the molecular mechanism(s) underlying this phenomenon remain unclear, abnormal transmission and plasticity of hippocampal synapses may play a key role in the pathoetiology of MDD. Methods: A chronic mild stress (CMS) protocol was applied to separate susceptible and unsusceptible rat subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation (iTRAQ) coupled with tandem mass spectrometry was performed to identify differential proteins in enriched hippocampal synaptic junction preparations. Results: A total of 4318 proteins were quantified, and 89 membrane proteins were present in differential amounts. Of these, SynaptomeDB identified 81 (91%) having a synapse-specific localization. The unbiased profiles identified several candidate proteins within the synaptic junction that may be associated with stress vulnerability or insusceptibility. Subsequent functional categorization revealed that protein systems particularly involved in membrane trafficking at the synaptic active zone exhibited a positive strain as potential molecular adaptations in the unsusceptible rats. Moreover, through STRING and immumoblotting analysis, membrane-associated GTP-bound Rab3a and Munc18-1 appear to co-regulate syntaxin-1/SNAP25/VAMP2 assembly at the hippocampal presynaptic active zone of unsusceptible rats, facilitating SNARE-mediated membrane fusion and neurotransmitter release, and may be part of a stress-protection mechanism in actively maintaining an emotional homeostasis. Conclusions: The present results support the concept that there are a range of potential protein adaptations in the hippocampal synaptic active zone of unsusceptible rats, revealing new investigative targets that may contribute to a better understanding of stress insusceptibility.

Dataset Information

IDA-SWATH proteomic analysis of rat hippocampus upon methylglyoxal treatment

Publications

Behavioral and Proteomic Studies Reveal Methylglyoxal Activate Pathways Associated with Alzheimer's Disease.

Similar Datasets

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