Biology subjects

Sharp, J. L.

Publications and source records attributed to Sharp, J. L..

3 recordsLinked to original sources

bioRxiv2020

The Effects of Strain and Estrous Cycle on Heroin- and Sucrose-Maintained Responding in Female Rats

Heroin intake decreases during the proestrus phase of the estrous cycle in female, Long-Evans rats. The purpose of this study was to (1) determine if proestrus-induced decreases in heroin intake extend across rat strains and (2) determine if proestrus-induced decreases in responding extend to a nondrug reinforcer. Female rats were implanted with intravenous catheters and trained to self-administer heroin. Estrous cycle was tracked daily for the duration of the study. During testing, Lewis, Sprague-Dawley, and Long Evans rats self-administered low (0.0025 mg/kg) and high (0.0075 mg /kg) doses of heroin (Experiment 1) and then self-administered sucrose (Experiment 2) on fixed ratio (FR1) schedules of reinforcement. Heroin intake decreased significantly during proestrus in all three rat strains under at least one dose condition; however, sucrose intake did not decrease during proestrus in any strain. These data indicate that responding maintained by heroin, but not a nondrug reinforcer, significantly decreases during proestrus in female rats and that these effects are consistent across rat strain.

animal behavior and cognition↗

bioRxiv2019

Immune, Autonomic, and Endocrine Dysregulation in Autism and Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorders Versus Unaffected Controls

BackgroundA growing body of literature suggests etiological overlap between Ehlers-Danlos syndrome (EDS)/hypermobility spectrum disorders (HSD) and some cases of autism, although this relationship is poorly delineated. In addition, immune, autonomic, and endocrine dysregulation are reported in both conditions and may be relevant to their respective etiologies.\n\nAimsTo study symptom overlap in these two comorbid spectrum conditions.\n\nMethods and ProceduresWe surveyed 702 adults aged 25+ years on a variety of EDS/HSD-related health topics, comparing individuals with EDS/HSD, autism, and unaffected controls.\n\nOutcomes and ResultsThe autism group reported similar though less severe symptomology as the EDS/HSD group, especially in areas of immune/autonomic/endocrine dysregulation, connective tissue abnormalities (i.e., skin, bruising/bleeding), and chronic pain. EDS/HSD mothers with autistic children reported more immune symptoms than EDS/HSD mothers without, suggesting the maternal immune system could play a heritable role in these conditions (p = 0.0119).\n\nConclusions and ImplicationsThese data suggest that EDS/HSD and autism share aspects of immune/autonomic/endocrine dysregulation, pain, and some tissue fragility, which is typically more severe in the former. This overlap, as well as documented comorbidity, suggests some forms of autism may be hereditary connective tissue disorders (HCTD).

neuroscience↗

bioRxiv2017

Widespread Genotype-Phenotype Correlations in Intellectual Disability

BackgroundLinking genotype to phenotype is a major aim of genetics research, yet many complex conditions continue to hide their underlying biochemical mechanisms. Recent research provides evidence that relevant gene-phenotype associations are discoverable in the study of intellectual disability (ID). Here we expand on that work, identifying distinctive gene interaction modules with unique enrichment patterns reflective of associated clinical features in ID.\n\nMethodsTwo hundred twelve forms of monogenic ID were curated according to comorbidities with autism and epilepsy. These groups were further subdivided according to secondary clinical symptoms of complex versus simple facial dysmorphia and neurodegenerative-like features due to their clinical prominence, modest symptom overlap, and probable etiological divergence. An aggregate gene interaction ID network for these phenotype subgroups was discovered using via a public database of known gene interactions: protein-protein, genetic, and mRNA coexpression. Additional annotation resources (Gene Ontology, Human Phenotype Ontology, TRANSFAC/JASPAR, and KEGG/WikiPathways) were utilized to assess functional and phenotypic enrichment modules within the full ID network.\n\nResultsPhenotypic analysis revealed high rates of complex facial dysmorphia in ID with comorbid autism. In contrast, neurodegenerative-like features were overrepresented in ID with epilepsy. Network analysis subsequently showed that gene groups divided according to clinical features of interest resulted in distinctive interaction clusters, with unique functional enrichments according to module.\n\nConclusionsThese data suggest that specific comorbid and secondary clinical features in ID are predictive of underlying genotype. In summary, ID form unique clusters, which are comprised of individual conditions with remarkable genotypic and phenotypic overlap.

genetics↗