Single channel properties of pannexin-1 and connexin-43 hemichannels and P2X7 receptors in astrocytes cultured from rodent spinal cords.

Astrocytes express surface channels involved in purinergic signaling. Among these channels, pannexin-1 (Px1) and connexin-43 (Cx43) hemichannels (HCs) release ATP that acts directly, or through its derivatives, on neurons and glia via purinergic receptors. Although HCs are functional, that is, open and close under physiological and pathological conditions, single channel properties of Px1 HCs in astrocytes have not been defined.

P2X7 receptor inhibition ameliorates dendritic spine pathology and social behavioral deficits in Rett syndrome mice.

Dysregulated immunity has been implicated in the pathogenesis of neurodevelopmental disorders but its contribution to synaptic and behavioral deficits in Rett syndrome (RTT) remains unknown. P2X7 receptors (P2X7Rs) are unique purinergic receptors with pro-inflammatory functions. Here, we report in a MECP2-deficient mouse model of RTT that the border of the cerebral cortex exhibits increased number of inflammatory myeloid cells expressing cell-surface P2X7Rs.

Contributions of monocytes to nervous system disorders.

Monocytes are a class of leukocytes derived from progenitors in the bone marrow and are prevalent in the blood stream. Although the main function of monocytes is to provide innate immune defenses against infection and injury, their contributions to the central nervous system (CNS) disorders are increasingly recognized. In this review article, we summarize the molecular and physiological properties of monocytes in relation to other myeloid cells.

CX3CR1 monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α.

Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy.

An Acute Mouse Spinal Cord Slice Preparation for Studying Glial Activation .

Pathological conditions such as amyotrophic lateral sclerosis, spinal cord injury and chronic pain are characterized by activation of astrocytes and microglia in spinal cord and have been modeled in rodents. imaging at cellular level in these animal models is limited due to the spinal cord's highly myelinated funiculi. The preparation of acute slices may offer an alternative and valuable strategy to collect structural and functional information from dorsal, lateral and ventral regions of spinal cord.

FGF-1 Triggers Pannexin-1 Hemichannel Opening in Spinal Astrocytes of Rodents and Promotes Inflammatory Responses in Acute Spinal Cord Slices.

Unlabelled: We show here that the growth factor FGF-1 is proinflammatory in the spinal cord and explore the inflammatory mechanisms. FGF-1 applied to rat spinal astrocytes in culture initiates calcium signaling and induces secretion of ATP that within minutes increases membrane permeability to ethidium (Etd(+)) and Ca(2+) by activating P2X7 receptors (P2X7Rs) that open pannexin hemichannels (Px1 HCs) that release further ATP; by 7 h treatment, connexin 43 hemichannels (Cx43 HCs) are also opened. In acute mouse spinal cord slices ex vivo, we found that FGF-1 treatment for 1 h increases the percentage of GFAP-positive astrocytes that show enhanced Px1 HC-mediated Etd(+) uptake.

Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury.

Spinal cord injury (SCI) is often complicated by secondary injury as a result of the innate inflammatory response to tissue trauma and swelling. Previous studies have shown that excessive ATP release from peritraumatic regions contributes to the inflammatory response to SCI by activation of low-affinity P2X7 receptors. Because connexin hemichannels constitute an important route for astrocytic ATP release, we here evaluated the impact on post-traumatic ATP release of deletion of connexins (Cx30/Cx43) in astrocytes.