Neuron to Astrocyte Communication via Cannabinoid Receptors Is Necessary for Sustained Epileptiform Activity in Rat Hippocampus

Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus

Tar DNA Binding Protein-43 (TDP-43) Associates with Stress Granules: Analysis of Cultured Cells and Pathological Brain Tissue

Tar DNA Binding Protein-43 (TDP-43) is a principle component of inclusions in many cases of frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). TDP-43 resides predominantly in the nucleus, but in affected areas of ALS and FTLD-U central nervous system, TDP-43 is aberrantly processed and forms cytoplasmic inclusions. The mechanisms governing TDP-43 inclusion formation are poorly understood. Increasing evidence indicates that TDP-43 regulates mRNA metabolism by interacting with mRNA binding proteins that are known to associate with RNA granules. Here we show that TDP-43 can be induced to form inclusions in cell culture and that most TDP-43 inclusions co-localize with SGs. SGs are cytoplasmic RNA granules that consist of mixed protein - RNA complexes. Under stressful conditions SGs are generated by the reversible aggregation of prion-like proteins, such as TIA-1, to regulate mRNA metabolism and protein translation. We also show that disease-linked mutations in TDP-43 increased TDP-43 inclusion formation in response to stressful stimuli. Biochemical studies demonstrated that the increased TDP-43 inclusion formation is associated with accumulation of TDP-43 detergent insoluble complexes. TDP-43 associates with SG by interacting with SG proteins, such as TIA-1, via direct protein-protein interactions, as well as RNA-dependent interactions. The signaling pathway that regulates SGs formation also modulates TDP-43 inclusion formation. We observed that inclusion formation mediated by WT or mutant TDP-43 can be suppressed by treatment with translational inhibitors that suppress or reverse SG formation. Finally, using Sudan black to quench endogenous autofluorescence, we also demonstrate that TDP-43 positive-inclusions in pathological CNS tissue co-localize with multiple protein markers of stress granules, including TIA-1 and eIF3. These data provide support for accumulating evidence that TDP-43 participates in the SG pathway

Bowser Response Letter to 'The Santa Clara'

Three page letter dated February 23, 1986 from Benjamin P. Bowser, Former Director of Black Affairs, to 'The Santa Clara' student newspaper, in response to an article titled 'Minority Advisory Committee Resigns,' published in the February 13, 1986 issue of the paper. Letter is from record group 5EM, Accession #993-058, Box 3, Folder 'Minority Committee 1983-86.

Ongoing Genocides and the Need for Healing: The Cases of Native and African Americans

The elimination of Native peoples and the enslavement of Africans in the U.S. more than qualify as acts of historical state sponsored genocide. A feature of both genocides is that they ended as institutional practices but have continued culturally and psychologically. The primary contemporary legacy of these genocides is racism which reinforces historical trauma and grief. Suggestions are made for how healing for Native and African Americans can begin despite ongoing racism. This includes psychological counseling for White Americans with beliefs in White supremacy. Suggestions are also made for how reconciliation can begin at the county-level between descendants of slave owners and enslaved Africans as well as between descendants of settlers and Native Americans

Intersecting Epidemics -- Crack Cocaine Use and HIV Infection among Inner-City Young Adults

“Crack” cocaine, an addictive, smokable form of cocaine, gained widespread use in many urban neighborhoods in the United States in the mid-1980s, particularly among poor young adults who were members of minority groups 1 – 6 . A recent national household survey of drug use found that approximately 1 million Americans, including 1.0 percent of those between 18 and 25 years of age, had used crack during the previous year 7 . Unlike injection-drug use, which is practiced predominantly by men, the use of crack cocaine is widespread among both men and women 7 – 9 . When inhaled, vaporized cocaine base gains rapid access . .