Dataset Information

Deep proteomic analysis of human hippocampus micro-sections provides a new avenue to identify hippocampal subfield heterogeneity in the protein expression

ABSTRACT: Hippocampus has drawn an immense attention from researchers and clinicians worldwide due to its clinical importance in various neurodegenerative disorders. Each hippocampal subfield is known to perform distinct functions and are selectively vulnerable to environmental, physiological, and clinical factors. Therefore, proteomic analysis of hippocampus at subfield level is increasingly important, however, an in-depth proteomic analysis of human hippocampus at its subfield level is not well established to date. In this study, we compared the sub-proteome of the hippocampus- the cornu ammonis sectors (CA1, CA2, CA3 and CA4), and dentate gyrus (DG) from healthy adult human cohorts using high resolution mass spectrometry. We procured hippocampal subfields from the archived FFPE tissue sections by performing manual micro-dissection and conducted TMT label quantification-based proteomic analysis that resulted in the identification of 5,593 proteins, of which 890 proteins were differentially abundant at ≥1.5-fold cut-off across all subfields. Gene Ontology enrichment analysis was performed to uncover the biological processes, pathways and cellular localization associated with each subfield of hippocampus. IHC-based validation of selected proteins were also carried out in an independent set of hippocampus from normal subjects. We believe that our findings will effectively pave a way for further analysis of the hippocampal subdivisions and understand the etiopathology of many neurological disorders in future.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Keshava Prasad T. S.

LAB HEAD: Dr. T. S. Keshava Prasad

PROVIDER: PXD029697 | Pride | 2022-10-14

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 37

Publications

Proteomic Analysis of Adult Human Hippocampal Subfields Demonstrates Regional Heterogeneity in the Protein Expression.

Mol Praseeda P Gopalakrishnan Lathika L Chatterjee Oishi O Mangalaparthi Kiran K KK Kumar Manish M Durgad Shwetha S SS Nair Bipin B Shankar Susarla K SK Mahadevan Anita A Prasad Thottethodi Subrahmanya Keshava TSK

Journal of proteome research 20220830 10

<b>Background:</b> Distinct hippocampal subfields are known to get affected during aging, psychiatric disorders, and various neurological and neurodegenerative conditions. To understand the biological processes associated with each subfield, it is important to understand its heterogeneity at the molecular level. To address this lacuna, we investigated the proteomic analysis of hippocampal subfields─the cornu ammonis sectors (CA1, CA2, CA3, CA4) and dentate gyrus (DG) from healthy adult human coh ...[more]

PMID: 36039803

Similar Datasets

Project description:Alzheimer’s disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, how this metabolic interplay may be affected during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in hippocampal brain slices of 5xFAD mice. This hyperactive neuronal phenotype coincided with decreased hippocampal TCA cycle metabolism mapped by stable 13C isotope tracing. Particularly, reduced astrocyte TCA cycle activity led to decreased glutamine synthesis, in turn hampering neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, cerebral cortical slices of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism suggesting a metabolic compensation. When we explored the brain proteome and metabolome of the 5xFAD mice, we found limited changes, supporting that the functional metabolic disturbances between neurons and astrocytes are early events in AD pathology. In addition, we show that synaptic mitochondrial and glycolytic function was impaired selectively in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex region and cell specific metabolic adaptations, in the early stages of amyloid pathology, which may be fundamental for the progressing synaptic dysfunction in AD.

Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.

			Action	DRS
	Hippo-N-F10_R1.raw	Raw
	Hippo-N-F10_R2.raw	Raw
	Hippo-N-F10_R3.raw	Raw
	Hippo-N-F11_R1.raw	Raw
	Hippo-N-F11_R2.raw	Raw