Omid Rahimi

Morphological development and maturation of granule neuron dendrites in the rat dentate gyrus

The first granule neurons in the dentate gyrus are born during late embryogenesis in the rodent, and the primary period of granule cell neurogenesis continues into the second postnatal week. On the day of birth in the rat, the oldest granule neurons are visible in the suprapyramidal blade and exhibit rudimentary dendrites extending into the molecular layer. Here we describe the morphological development of the dendritic trees between birth and day 14, and we then review the process of dendritic remodeling that occurs after the end of the second week. Data indicate that the first adult-like granule neurons are present on day 7, and, furthermore, physiological recordings demonstrate that some granule neurons are functional at this time. Taken together, these results suggest that the dentate gyrus may be incorporated into the hippocampal circuit as early as the end of the first week. The dendritic trees of the granule neurons, however, continue to increase in size until day 14. After that time, the dendritic trees of the oldest granule neurons are sculpted and refined. Some dendrites elongate while others are lost, resulting in a conservation of total dendritic length. We end this chapter with a review of the quantitative aspects of granule cell dendrites in the adult rat and a discussion of the relationship between the morphology of a granule neuron and the location of its cell body within stratum granulosum and along the transverse axis of the dentate gyrus.

Radiofrequency-Radiation Exposure Does Not Induce Detectable Leakage of Albumin Across the Blood-Brain Barrier

Abstract McQuade, J. M., Merritt, J. H., Miller, S. A., Scholin, T., Cook, M. C., Salazar, A., Rahimi, O. B., Murphy, M. R. and Mason, P. A. Radiofrequency-Radiation Exposure Does Not Induce Detectable Leakage of Albumin Across the Blood-Brain Barrier. Radiat. Res. 171, 615–621 (2009). The blood-brain barrier (BBB) consists of tight junctions between the endothelial cells that line the capillaries in the central nervous system. This structure protects the brain, and neurological damage could occur if it is compromised. Several publications by researchers at Lund University have reported alterations in the BBB after exposure to low-power 915 MHz energy. These publications increased the level of concern regarding the safety of wireless communication devices such as mobile phones. We performed a confirmation study designed to determine whether the BBB is altered in rats exposed in a transverse electromagnetic (TEM) transmission line cell to 915 MHz energy at parameters similar to those in the Lund University studies. Unanesthetized rats were exposed for 30 min to either continuous-wave or modulated (16 or 217 Hz) 915 MHz energy at power levels resulting in whole-body specific absorption rates (SARs) of 0.0018–20 W/kg. Albumin immunohistochemistry was performed on perfused brain tissue sections to determine the integrity of the BBB. Chi-square analysis revealed no significant increase in albumin extravasation in any of the exposed animals compared to the sham-exposed or home cage control animals.

Nerve growth factor increases stimulus-evoked metabolic activity in acetylcholine-depleted barrel cortex.

Lesions of the basal forebrain deplete the neocortex of cholinergic fibers. Acetylcholine depletion in the somatosensory cortex of rats results in reduced stimulus-evoked activity in response to whisker stimulation. Previous studies demonstrate that embryonic basal forebrain transplants improve functional activity toward normal. It is not clear if the activity increase is due to cholinergic replacement or other factors present in the graft. In this study, we examined the possibility that nerve growth factor (NGF), a neurotrophin known as a survival factor and a specific protectant for cholinergic basal forebrain neurons, can preserve basal forebrain cells after a lesion and restore functional activity in the somatosensory cortex. We report that NGF alone is capable of restoring functional activity in the barrel cortex of animals with basal forebrain lesions, while vehicle injections of saline do not alter activity. Both high (10 microg) and low (5 microg) doses of NGF unilaterally injected into the lateral ventricle improved stimulus-evoked functional activity during bilateral whisker stimulation. The mechanism of NGF action is not clear since the restoration of functional activity in cortex was not accompanied by increased cholinergic activity as detected by acetylcholinesterase fiber staining. NGF may act directly on cortical neurons, although its site of action is not well defined.

In Vivo and In Silico Evidence: Hippocampal Cholesterol Metabolism Decreases with Aging and Increases with Alzheimers Disease -- Modeling Brain Aging and Disease

Genome wide association studies revealed genetic evidence for involvement of cholesterol metabolism in the etiology of Alzheimers disease (AD). The present study used gene expression profiles on human Cornu Ammonis 1(CA1) for subjects with severe AD and an age-matched group to determine the enzyme reaction rate constants for 16 core metabolic pathways including cholesterol biosynthesis, isoprenoid production, and cholesterol catabolism for removal from brain. The core metabolic model was used to simulate a young hippocampus (20-39yo) to compare with age-matched control group for our AD study (mean= 85.3y). In the aged human brain, the flux through the rate limiting step in the simulation for aged human hippocampus was lower by 9.5%, the cholesterol level was 52.3% lower in the simulation and 33.6% lower in the aged human brain, validating the in silico method. Data was also used to evaluate sterol regulatory element binding protein 1 and 2 (SREBP1 & SREBP2) showing the levels were increased significantly in the severe AD samples versus age-matched control. We predicted that the core metabolism simulation of severe AD versus age-matched control would show corresponding results and they do. The sensitivities analyses for incipient and severe AD demonstrated how they differ: Most reactions are insensitive for severe AD and two sensitive peaks are obvious, cholesterol and ubiquinone levels are most sensitive to cholesterol 24-hydroxylase, CYP46a1. These findings are consistent with statins being ineffective in clinical trials for treatment of AD, post-diagnosis.

Transcriptome-to-reactome biosimulation: Basal forebrain cholinergic neuron neurotrophin signaling

PKA. Conclusions: Because tau phosphorylation at Ser214 may prime tau for further phosphorylation by other kinases, our findings provide a novel possible mechanism by which rapamycin reduces or prevents tau hyperphosphorylation. P3-035 TRANSCRIPTOME-TO-REACTOME BIOSIMULATION: BASAL FOREBRAIN CHOLINERGIC NEURON NEUROTROPHIN SIGNALING Clyde Phelix, Omid Rahimi, Luis Colom, George Perry, Stephen Ginsberg, University of Texas at San Antonio, San Antonio, Texas, United States; University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States; University of Texas at Brownsville, Brownsville, Texas, United States; 4 New York University Langone Medical Center, Orangeburg, New York, United States.