Dataset Information

Neuroproteomics with Systems Biology: The proteomic landscape of adult human hypothalamus

ABSTRACT: The hypothalamus is an anatomically small, but functionally crucial region of the human brain. Normal hypothalamus functioning is central to the regulation of neuroendocrine and neurovegetative systems as well as modulation of chronobiology and behavioral aspects of the human body. Till date the human hypothalamus proteome profile is lacking from literature. In this study, we attempt to delineate the human hypothalamus proteome using high-resolution mass spectrometry approach. We identified a total of 5,349 proteins in the proteomics study. The unassigned spectra from the proteomics study were further used for identifying multiple post translational modification sites as well as for proteogenomics analysis. This resulted in the identification of 616 additional proteins. We observed a higher representation of mitochondrial and synaptic proteins in the proteomics data, as well as enrichment of pathways supporting the hypothalamic involvement in autophagy and adult neurogenesis. Interestingly, the phospholipase D signaling pathway emerged as a junction to the various aspects of hypothalamic functions, and relation to neurodegenerative disorders. Additionally, the investigation for multiple post translational modifications led to the identification of several known and novel post translational modification sites. A total of 13,544 peptides corresponding to 2,542 proteins with modifications of R/K-methylation, S/T/Y-phosphorylation, N/Q-deamidation, R-citrullination, and K-acetylation have been reported in this study. Proteogenomic analysis of hypothalamus resulted in the identification of 291 GSSPs which were further categorised into probable gene correction events. Among these, we confirmed 28 peptides to confer evidence for 10 predicted pseudogenes with coding potential, 4 novel protein-coding (3 novel isoforms, and 1 novel SEP), and 3 protein correction (1 novel exon, 1 alternate frame of translation and 1 N-terminal protein extension) events. We believe that hypothalamic proteome would aid as a platform to decipher the molecular basis for the diverse range of functions performed by this region and provide a baseline for exploring the role of these proteins in neurological health and disorders.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Keshava Prasad T. S.

LAB HEAD: Thottethodi Subrahmanya Keshava Prasad

PROVIDER: PXD026879 | Pride | 2021-11-01

REPOSITORIES: Pride

ACCESS DATA

Publications

The Normal Human Adult Hypothalamus Proteomic Landscape: Rise of Neuroproteomics in Biological Psychiatry and Systems Biology.

Chatterjee Oishi O Gopalakrishnan Lathika L Mol Praseeda P Advani Jayshree J Nair Bipin B Shankar Susarla Krishna SK Mahadevan Anita A Prasad Thottethodi Subrahmanya Keshava TSK

Omics : a journal of integrative biology 20211029 11

The human hypothalamus is central to the regulation of neuroendocrine and neurovegetative systems, as well as modulation of chronobiology and behavioral aspects in human health and disease. Surprisingly, a deep proteomic analysis of the normal human hypothalamic proteome has been missing for such an important organ so far. In this study, we delineated the human hypothalamus proteome using a high-resolution mass spectrometry approach which resulted in the identification of 5349 proteins, while a ...[more]

PMID: 34714154

Similar Datasets

Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.

Project description:Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked ACTH and by reproduction. Genome-wide microarrays in sodium deficient mice, or following ACTH infusion, showed upregulation of hypothalamic genes, including DARPP-32, dopamine receptors-1 and -2, alpha-2C-adrenoceptor, and STEP. Both DARPP-32 and neural plasticity regulator, ARC were upregulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1- (SCH23390) and D2-receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1-receptor knockout mice had normal sodium appetite, indicating compensatory regulation. It was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100nM in 200nL) into rats? lateral hypothalamus greatly reduced sodium appetite. Gene Set Enrichment Analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates, cocaine). This finding of concerted gene regulation was attenuated upon gratification with perplexingly rapid kinetics of only 10 minutes, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over more than a hundred million years e.g. being present in Metatheria. Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a novel molecular logic for instinctive behavior encoded by the brain with possible important translational-medical implications. Transcripts were profiled in the hypothalamus and whole brain of control and salt craving animals to determine the gene expression profile corresponding to that behavioral state. We show an over-representation of addiction-related genes in the set that is common to different methods of salt craving. Mouse hypothalamus and whole brain under three conditions: control, furosemide treated, and ACTH treated. 4 or 5 biological replicated per group. Two channels - experimental and reference are used.

Dataset Information

Neuroproteomics with Systems Biology: The proteomic landscape of adult human hypothalamus

Publications

The Normal Human Adult Hypothalamus Proteomic Landscape: Rise of Neuroproteomics in Biological Psychiatry and Systems Biology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure