Lactic acid inhibition of gap junctional intercellular communication in in vitro astrocytes as measured by fluorescence recovery after laser photobleaching

Anders, Juanita J.

doi:10.1002/glia.440010604

Cited by 55 publications

(30 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is thought to occur through the development of discrete gap junction linked clusters of neurons [88,104] . Furthermore closure of glial gap junctions by PPA could lead to neuronal hyperexcitablilty by impaired glial spatial buffering of cytosolic potassium or glutamate [105] . Moreover, intrastriatal infusions of gap junction blockers produce movement disorder in rodents [106] .…”

Section: Fig 6: Group Means (±Sem) For (A) Glutathione (Gsh) (B) Glmentioning

confidence: 99%

A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

MacFabe¹,

Rodríguez-Capote²,

Hoffman³

et al. 2008

American J. of Biochemistry and Biotechnology

View full text Add to dashboard Cite

Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD). Propionic acid (PPA) is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats. Adult Long-Evans rats were given intraventricular infusions of either PPA (.26M, 4µl animal −1 ) or phosphate buffered saline (PBS)vehicle, twice daily for 7 days. Immediately following the second daily infusion, the locomotor activity of each rat was assessed in an automated open field (Versamax) for 30 min. PPA-treated rats showed significant increases in locomotor activity compared to PBS vehicle controls. Following the last treatment day, specific brain regions were assessed for neuroinflammatory or oxidative stress markers. Immunohistochemical analyses revealed reactive astrogliosis (GFAP), activated microglia (CD68, Iba1) without apoptotic cell loss (Caspase 3' and NeuN) in hippocampus and white matter (external capsule) of PPA treated rats. Biomarkers of protein and lipid peroxidation, total glutathione (GSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were examined in brain homogenates. Some brain regions of PPA treated animals (neocortex, hippocampus, thalamus, striatum) showed increased lipid and protein oxidation accompanied by decreased total GSH in neocortex. Catalase activity was decreased in most brain regions of PPA treated animals suggestive of reduced antioxidant enzymatic activity. GPx and GR activity was relatively unaffected by PPA treatment while GST was increased, perhaps indicating involvement of GSH in the removal of PPA or related catabolites. Impairments in GSH and catalase levels may render CNS cells more susceptible to oxidative stress from a variety of toxic insults. Overall, these findings are consistent with those found in ASD patients and further support intraventricular PPA administration as an animal model of ASD.

show abstract

Section: Fig 6: Group Means (±Sem) For (A) Glutathione (Gsh) (B) Glmentioning

confidence: 99%

A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

MacFabe¹,

Rodríguez-Capote²,

Hoffman³

et al. 2008

American J. of Biochemistry and Biotechnology

View full text Add to dashboard Cite

show abstract

“…Data about the sensitivity of astrocytic junctions to pH are conflicting. Anders et al (1988) found that astrocytic uncoupling first occurred when extracellular pH was lowered to 4.5 by exposure to a lactic acid-containing solution. The degree of intracellular acidosis that develops during this exposure is lethal to cultured astrocytes , suggesting that pH in the physiological range does not regulate coupling.…”

Section: Calcium and Hydrogen Ions As Modulators Of Gap Junctional Pementioning

confidence: 99%

Astrocytic Gap Junctions Remain Open during Ischemic Conditions

et al. 1998

View full text Add to dashboard Cite

Gap junctions are highly conductive channels that allow the direct transfer of intracellular messengers such as Ca 2ϩ and inositol triphosphate (IP 3 ) between interconnected cells. In brain, astrocytes are coupled extensively by gap junctions. We found here that gap junctions among astrocytes in acutely prepared brain slices as well as in culture remained open during ischemic conditions. Uncoupling first occurred after the terminal loss of plasma membrane integrity. Gap junctions therefore may link ischemic astrocytes in an evolving infarct with the surroundings. The free exchange of intracellular messengers between dying and potentially viable astrocytes might contribute to secondary expansion of ischemic lesions.

show abstract

“…Injection of the low molecular weight fluorescent dye Lucifer yellow (LY) (3) into single astrocytes has revealed dye spread into adjacent astrocytes, thereby indicating gap junctional communication, in cortical slices (4), spinal cord (5), cortical (6) and cerebellar cell cultures (7), and rat optic nerve (RON) in situ (8). Similarly, coupling of cultured astrocytes was apparent in studies in which laser photobleaching techniques were used (9).…”

Section: Introductionmentioning

confidence: 99%

Specificity of cell-cell coupling in rat optic nerve astrocytes in vitro.

Sontheimer

Minturn

Black

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Intercellular coupling was studied in cultured rat optic nerve astrocytes individually characterized by A2B5 antibody staining. The presence ofcell coupling was assessed by injecting single cells with the low molecular weight fluorescent dye Lucifer yellow and noting dye passage into adjacent cells; cell coupling was also studied by analyzing the decay phase of current transients recorded in response to small voltage steps using whole-cell patch-clamp recording. Cell coupling was restricted to A2B5-astrocytes, the majority of which had a flat fibroblast-like appearance and was never observed in A2B5+ stellate-shaped astrocytes. Furthermore, A2B5-astrocytes showed coupling only to A2B5-and never to A2B5' astrocytes.Analysis of current transients provided an additional indicator for cell coupling. Astrocytes that showed dye coupling to at least one neighboring cell required the sum of two exponential functions to fit current transients, whereas a single exponential function sufficed to fit transients in cells that were not dye coupled. The specificity of cell coupling in cultured rat optic nerve astrocytes suggests that predominantly A2B5-astrocytes comprise a coupled glial syncytium; this physiological feature of these cells may be a specialized adaptation for "spatial buffering," the transport of K+ away from areas of focal extracellular accumulation. On the other hand, A2B5M astrocytes form an uncoupled subpopulation of rat optic nerve glial cells that may serve different functions.Astrocytes form gap junctions with adjacent astrocytes (1) and these large intercellular channels are believed to link the cells into a three-dimensional network. As previously shown for a variety of cell systems, these connections allow direct cytoplasmic diffusion of inorganic and small organic molecules between cells (2). Injection of the low molecular weight fluorescent dye Lucifer yellow (LY) (3) into single astrocytes has revealed dye spread into adjacent astrocytes, thereby indicating gap junctional communication, in cortical slices (4), spinal cord (5), cortical (6) and cerebellar cell cultures (7), and rat optic nerve (RON) in situ (8). Similarly, coupling of cultured astrocytes was apparent in studies in which laser photobleaching techniques were used (9).Cultures from RON provide a well-described glial cell system in which two types of astrocytes can be distinguished morphologically and by their ability to bind the monoclonal antibody A2B5 (reviewed in ref. 10). In vitro A2B5-/GFAP+ (glial fibrillary acidic protein) astrocytes [termed type 1 astrocytes, (11)] have a fibroblast-like appearance and are believed to develop from a specific, still poorly characterized, progenitor cell. In contrast, A2B5+/GFAP+ astrocytes [termed type 2 astrocytes (11)] have a stellate appearance and share a common precursor cell, the 02A progenitor cell, with oligodendrocytes (10,11). Further differences between these types of astrocytes have become apparent and include, but are not limited to, their response to and the secretion of gro...

show abstract

Lactic acid inhibition of gap junctional intercellular communication in in vitro astrocytes as measured by fluorescence recovery after laser photobleaching

Cited by 55 publications

References 41 publications

A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

Astrocytic Gap Junctions Remain Open during Ischemic Conditions

Specificity of cell-cell coupling in rat optic nerve astrocytes in vitro.

Contact Info

Product

Resources

About