Sex-Dependent Synaptic Remodeling of the Somatosensory Cortex in Mice With Prenatal Methadone Exposure.

Autor:	Grecco GG; Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis, IN, United States.; Medical Scientist Training Program, School of Medicine, Indiana University, Indianapolis, IN, United States., Huang JY; The Linda and Jack Gill Center for Biomolecular Sciences, Indiana University, Bloomington, IN, United States.; Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States., Muñoz B; Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis, IN, United States., Doud EH; Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University, Indianapolis, IN, United States., Hines CD; The Linda and Jack Gill Center for Biomolecular Sciences, Indiana University, Bloomington, IN, United States., Gao Y; Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis, IN, United States., Rodriguez B; Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis, IN, United States., Mosley AL; Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University, Indianapolis, IN, United States., Lu HC; The Linda and Jack Gill Center for Biomolecular Sciences, Indiana University, Bloomington, IN, United States.; Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States., Atwood BK; Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis, IN, United States.; Stark Neurosciences Research Institute, School of Medicine, Indiana University, Indianapolis, IN, United States.
Jazyk:	angličtina
Zdroj:	Advances in drug and alcohol research [Adv Drug Alcohol Res] 2022 Apr; Vol. 2. Date of Electronic Publication: 2022 Apr 25.
DOI:	10.3389/adar.2022.10400
Abstrakt:	Rising opioid use among pregnant women has led to a growing population of neonates exposed to opioids during the prenatal period, but how opioids affect the developing brain remains to be fully understood. Animal models of prenatal opioid exposure have discovered deficits in somatosensory behavioral development that persist into adolescence suggesting opioid exposure induces long lasting neuroadaptations on somatosensory circuitry such as the primary somatosensory cortex (S1). Using a mouse model of prenatal methadone exposure (PME) that displays delays in somatosensory milestone development, we performed an un-biased multi-omics analysis and investigated synaptic functioning in the primary somatosensory cortex (S1), where touch and pain sensory inputs are received in the brain, of early adolescent PME offspring. PME was associated with numerous changes in protein and phosphopeptide abundances that differed considerably between sexes in the S1. Although prominent sex effects were discovered in the multi-omics assessment, functional enrichment analyses revealed the protein and phosphopeptide differences were associated with synapse-related cellular components and synaptic signaling-related biological processes, regardless of sex. Immunohistochemical analysis identified diminished GABAergic synapses in both layer 2/3 and 4 of PME offspring. These immunohistochemical and proteomic alterations were associated with functional consequences as layer 2/3 pyramidal neurons revealed reduced amplitudes and a lengthened decay constant of inhibitory postsynaptic currents. Lastly, in addition to reduced cortical thickness of the S1, cell-type marker analysis revealed reduced microglia density in the upper layer of the S1 that was primarily driven by PME females. Taken together, our studies show the lasting changes on synaptic function and microglia in S1 cortex caused by PME in a sex-dependent manner. Competing Interests: CONFLICT OF INTEREST The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu