Brain research
-
Brain-derived neurotrophic factor (BDNF) expression changes in the dorsal root ganglion (DRG) and spinal cord in some pain models. Recently, rat BDNF transcripts containing novel 5' untranslated exons were identified and characterized, and a new numbering system for rat BDNF exons was introduced. We examined the expression profiles of these novel BDNF transcripts in bilateral L4/5 DRGs in an L5-selective spinal nerve ligation (SSNL) model and bilateral L5 DRGs in a complete Freund's adjuvant (CFA) model of rats. ⋯ The expression profiles of the variant exons in ipsilateral L4 DRG of the L5SSNL model were quite similar to those in ipsilateral DRG of the CFA model, and exon I transcript was the most common BDNF mRNA in these DRGs. Although L5SSNL increased significantly (P<0.05) the expression of total BDNF mRNA and exon IIC and IXA transcripts in the contralateral L4/5 DRGs, CFA treatment did not alter the expression of total BDNF mRNA or specific transcripts in the contralateral DRGs. These findings suggest that exon I plays an important role in the increase in BDNF expression in ipsilateral DRGs regardless of condition.
-
Ablation of the SCN, an established circadian clock, does not abolish food entrainment, suggesting that the food-entrainable oscillator (FEO) must lie outside the SCN. Typically, animals show anticipatory locomotor activity and rise in core body temperature under the influence of the FEO. Signals from the FEO would, therefore, converge onto arousal neurons so that the animal might forage for food. ⋯ In these mice gross locomotor activity was severely blunted during the nine day period of restricted feeding (-79.4+/-6.3%) from the WT, but they showed an increase in core body temperature in anticipation to the meal time similar to the WT mice. There was no difference in the amount of food intake between the genotypes. We conclude that orexin is not required for entrainment of activity and temperature to a restricted feeding schedule, but is required for the robust expression of gross locomotor activity in anticipation of the scheduled feeding.
-
Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble drugs. Given that DMSO has varying cellular and behavioral effects ranging from increased membrane permeability to toxicity, microinjection of DMSO as a vehicle could confound the effects of other drugs. For example, DMSO is often used as a vehicle for studies examining the neurochemical mechanisms underlying morphine antinociception. ⋯ Co-administration of morphine and DMSO during the pretreatment did not cause a greater shift in the morphine dose-response curve compared to morphine pretreated alone. In conclusion, DMSO can alter morphine antinociception following both acute (enhancement) and chronic (inhibition) administration depending on the concentration. These data reinforce the need to be cautious when using DMSO as a vehicle for drug administration.
-
Sodium valproate (VPA) administered to neonatal mice causes cognitive and motor deficits similar to those observed in humans with autism. In an effort to further evaluate similarities between early VPA exposure and autism, the present study examined treated mice for deficits in social behavior and neuronal damage. BALB/c mice injected on P14 with 400 mg/kg VPA engaged in fewer social interactions (including ano-genital sniffs, allogrooming, and crawl-under/over behaviors) than control mice. ⋯ A second set of BALB/c mice were treated with VPA on P14 and sacrificed at different times thereafter for histopathological analysis. At time-points 12 and 24 h following VPA, treated mice had up to a 30-fold increase in the number of TUNEL-positive cells in the external granule cell layer of the cerebellum and a 10-fold increase in TUNEL-positive cells in the dentate gyrus of the hippocampus. These observations may provide a histopathological correlate for the social deficits observed following post-natal VPA exposure and supports the use of early VPA administration as an animal model for the study of autism.
-
The pathogenesis of human immunodeficiency virus (HIV) associated encephalopathy is attributed to infiltration of the central nervous system (CNS) by HIV-1 infected mononuclear cells that transmigrate across the blood brain barrier (BBB). The endothelial tight junctions (TJ) of the blood brain barrier (BBB) play a critical role in controlling cellular traffic into the CNS. Neuropathogenesis of HIV-1 is exacerbated by drugs of abuse such as methamphetamine (Meth) which are capable of dysregulating BBB function. ⋯ Our results show that both Meth and gp120 individually and in combination, modulated TJ expression, and these effects involved Rho-A activation. Further, both Meth and gp120 alone and in combination significantly decreased transendothelial resistance across the in vitro BBB and the enhanced transendothelial migration of immunocompetent cells across the BBB. An understanding of the mechanisms of BBB breakdown that lead to neurotoxicity is crucial to the development of therapeutic modalities for Meth abusing HAD patients.