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Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

ABSTRACT: The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.

SUBMITTER: Ma S

PROVIDER: S-EPMC9614553 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

Ma Shaojie S Skarica Mario M Li Qian Q Xu Chuan C Risgaard Ryan D RD Tebbenkamp Andrew T N ATN Mato-Blanco Xoel X Kovner Rothem R Krsnik Željka Ž de Martin Xabier X Luria Victor V Martí-Pérez Xavier X Liang Dan D Karger Amir A Schmidt Danielle K DK Gomez-Sanchez Zachary Z Qi Cai C Gobeske Kevin T KT Pochareddy Sirisha S Debnath Ashwin A Hottman Cade J CJ Spurrier Joshua J Teo Leon L Boghdadi Anthony G AG Homman-Ludiye Jihane J Ely John J JJ Daadi Etienne W EW Mi Da D Daadi Marcel M Marín Oscar O Hof Patrick R PR Rasin Mladen-Roko MR Bourne James J Sherwood Chet C CC Santpere Gabriel G Girgenti Matthew J MJ Strittmatter Stephen M SM Sousa André M M AMM Sestan Nenad N

Science (New York, N.Y.) 20220930 6614

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural s ...[more]

PMID: 36007006

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Project description:BackgroundMethamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity.Materials and methodsIn this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content.ResultsThe expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Discussion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity.DiscussionOur study showed BDNF-positive cells as well as GSH amount, displayed significant declines in DLPFC of MA user. MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. However, further investigations are needed to throw light on the cellular and molecular mechanisms that act in the various regions of the addicted brain, especially in DLPFC.

Dataset Information

Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

Publications

Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

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