Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry

Production of Proinflammatory Cytokines and Chemokines During Neuroinflammation: Novel Roles for Estrogen Receptors α and β

Neuroinflammation is a common feature of many neurological disorders, and it is often accompanied by the release of proinflammatory cytokines and chemokines. Estradiol-17β (E2) exhibits antiinflammatory properties, including the suppression of proinflammatory cytokines, in the central nervous system. However, the mechanisms employed by E2 and the role(s) of estrogen receptors (ERs) ERα and ERβ are unclear. To investigate these mechanisms, we employed an in vivo lipopolysaccharide (LPS) model of systemic inflammation in ovariectomized (OVX) and OVX and E2-treated (OVX+E2) mice. Brain levels of proinflammatory cytokines (IL-1β, IL-6, and IL-12p40) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, and CXCL1/KC) were quantified in mice at 0 (sham), 3, 6, 12, and 24 h after infection using multiplex protein analysis. E2 treatment inhibited LPS-induced increases in all cytokines. In contrast, E2 treatment only suppressed CCL/RANTES chemokine concentrations. To determine whether ERα and ERβ regulate brain cytokine and chemokine levels, parallel experiments were conducted using ERα knockout and ERβ knockout mice. Our results revealed that both ERα and ERβ regulated proinflammatory cytokine and chemokine production through E2-dependent and E2-independent mechanisms. To assess whether breakdown of the blood-brain barrier is an additional target of E2 against LPS-induced neuroinflammation, we measured Evan’s blue extravasation and identified distinct roles for ERα and ERβ. Taken together, these studies identify a dramatic cytokine- and chemokine-mediated neuroinflammatory response that is regulated through ERα- and ERβ-mediated ligand-dependent and ligand-independent mechanisms