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Gender dimorphism in serotonin dopamine and norepinephrine neurons of isodendritc core in postmortem human and nonhuman primate control subjects
Author(s) -
Reddy Arubala P,
Sawant Neha,
Bunquin Lloyd S,
Reddy Hemachandra
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047366
Subject(s) - substantia nigra , dorsal raphe nucleus , locus coeruleus , neuroscience , monoaminergic , biology , raphe nuclei , midbrain , dopamine , serotonin , serotonergic , medicine , psychology , dopaminergic , genetics , central nervous system , receptor
Abstract Background Comorbidity of depression in bMets, NPSs and NDDs is resource demanding clinical area considering treatment challenges and patient care. NPSs represent prodromal symptoms of dementia results of neurobiological changes in specific subcortical region. Dynamic cascade of Aβ shifts from nonamyloidogenic is implicated in early cognitive impairment and depressive symptoms. Serotonergic system is implicated in Aβ pathology and NE is important to compensatory in Aβ degradation. Although the role of DA is not investigated in AD pathology. Overall neuromodulation in IDC of midbrain is imperative and intriguing aspect of monoaminergic association in AD and other NDDs pathology.Here we present genetic dimorphism of key area of the brain (5HT: dorsal raphe, DA:substantia nigra, Noradrenaline: locus ceruleous). Method 4males and 4 females midbrain of control subject were collected from Neurobiobank (NIH) and ONPRC. Brain sections were collected 20‐micron sections on cover glass plain slides. 4mm tissue punches were used to collect RNA from tissues. Enough tissues used to generate 10ug‐20 ug average quality RNA. 4ug RNA from Raphe, substantia nigra and locus ceruleous was isolated using trizol isolation and sent to UTSW microarray core. The RNA was hybridized to Clariom D Human chip and CEL chip data obtained from UTSW core. CEL files were uploaded in Transcriptome Analysis Console (TAC4.0). Statistically significant data in Excel file is uploaded in Ingenuity Pathway analysis software to find biological pathways dominate female and male brains. Microarray analysis of adult serotonin neurons in human and NHP dorsal raphe, Substantia nigra and Locus ceruleous (DR/SN/LC) Chip has expression of 500.000 known and unknown RNA species transcript encoding 135,000 RNA Result Human DR/SNC/LC have 6643/13475/9194 number of probe set and 850/896//501 pathways, and Rhesus DR/SNC/LC have 7261/2157/1938 probe sets and 872/218/198 pathways altered respectively with one or more genes. Major dominated pathways: electron transport chain. Oxidative phosphorylation, miRNA, mitochondria dysfunction, apoptosis signaling, will be presented in the poster Conclusion Major energy metabolism pathway dominates in all three area in male DR/SN/LC area clearly state female brain having lower energy metabolism may results in reduce homeostasis in Isodendritc core midbrain area. Although compensatory mechanism may still yet investigate.