Neuronal ablation of mt-AspRS in mice induces immune pathway activation prior to severe and progressive cortical and behavioral disruption.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare, slowly progressive white matter disease caused by mutations in the mitochondrial aspartyl-tRNA synthetase (mt-AspRS, or DARS2). While patients show characteristic MRI T2 signal abnormalities throughout the cerebral white matter, brainstem, and spinal cord, the phenotypic spectrum is broad and a multitude of gene variants have been associated with the disease. Here, Dars2 disruption in CamKIIα-expressing cortical and hippocampal neurons results in slowly progressive increases in behavioral activity at five months, and culminating by nine months as severe brain atrophy, behavioral dysfunction, reduced corpus callosum thickness, and microglial morphology indicative of neuroinflammation. Interestingly, RNAseq based gene expression studies performed prior to the presentation of this severe phenotype reveal the upregulation of several pathways involved in immune activation, cytokine production and signaling, and defense response regulation. RNA transcript analysis demonstrates that activation of immune and cell stress pathways are initiated in advance of a behavioral phenotype and cerebral deficits. An understanding of these pathways and their contribution to significant neuronal loss in CamKII-Dars2 deficient mice may aid in deciphering mechanisms of LBSL pathology.

Polichromic staining of five distinct cellular types in human and rat pituitaries

Se describe un método de tinción pentacrómico que permite identificar los diferentes tipos celulares en tejidos adenohipofisiario humano y de rata y en células dispersas de rata. Esta técnica mostró un grado suficiente de selectividad que hizo posible distinguir 5 tipos celulares: lactotropos (rojos), somatotropos (amarillos), tirotropos (azul intenso), corticotropos (violeta) y gonadotropos (verde). De las células dispersas de rata un 90% del total analizado estuvo representado por los 2 grupos de células acidófilas, mientras que el 10% restante correspondió a: tirotropos 1.7%, corticotropos 1.1% y gonadotropos casi 7.0%. En la estirpe acidófila las proporciones de los dos tipos celulares obtenidas mediante esta tinción (PRL 63.7%, CH 26.7%) fueron comparables a los datos informados en la literatura utilizando métodos inmunohistoquímicos. Cada uno de los cinco grupos de células estudiados fue a su vez subdividido en tres categorías dependiendo de su tamaño. El bajo costo y la selectividad del método permiten proponerlo como de gran utilidad para aquellas instituciones que carecen de instalaciones para realizar estudios inmunocitoquímicos o de microscopía electrónica