Dr. Loubna Erraji, PhD, MBA, PCC

Our findings indicate that a set of synaptic plasticity-related genes have their expression modulated during sleep following LTP, which can reflect biochemical events associated with reshaping of synaptic connections in sleep following learning.

In this report we demonstrate that, under normal physiological conditions, an increased beta 2-adrenergic receptor (B2-AR) activity affects the expression of the gluconeogenic and glycolytic key enzymes phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and L-pyruvate kinase and considerably decreases hepatic glycogen levels. Furthermore, we show that the effects of beta-adrenergic ligands on liver glycogen observed in humans are reproduced in our line of transgenic mice, F28, carrying… Show more

In this report we demonstrate that, under normal physiological conditions, an increased beta 2-adrenergic receptor (B2-AR) activity affects the expression of the gluconeogenic and glycolytic key enzymes phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and L-pyruvate kinase and considerably decreases hepatic glycogen levels. Furthermore, we show that the effects of beta-adrenergic ligands on liver glycogen observed in humans are reproduced in our line of transgenic mice, F28, carrying the human B2-AR human gene under the control of its own promoter: liver glycogen levels are strongly decreased by the B2-AR agonist clenbuterol and increased by the B-AR antagonist propranolol. These transgenic mice open new perspectives for studying in vivo the hepatic B2-AR system physiopathology and for testing the effects of B-AR ligands on liver metabolism. Show less

Genomics to identify biomarkers of normal brain aging.

Continuous changes in gene expression with increasing age revealed a "molecular profile" of aging in human PFC. The restricted scope of the transcript changes suggests cellular populations or functions that are selectively vulnerable during aging. Because age-related gene expression changes begin early in adulthood and are continuous throughout life, our results suggest the possibility of identifying early cellular mechanisms that may be engaged in preventive or detrimental age-related brain… Show more

Continuous changes in gene expression with increasing age revealed a "molecular profile" of aging in human PFC. The restricted scope of the transcript changes suggests cellular populations or functions that are selectively vulnerable during aging. Because age-related gene expression changes begin early in adulthood and are continuous throughout life, our results suggest the possibility of identifying early cellular mechanisms that may be engaged in preventive or detrimental age-related brain functions. Show less

We tested several hypotheses of disease pathology and of their putative molecular impact, including changes in single genes, the existence of subgroups of patients or disease subtypes, or the possibility of common biological pathways being affected in the disease process. Within the analytical limits of this relatively large genomic study, we found no evidence for molecular differences that correlated with depression and suicide, suggesting a pathology that is below the detection level of… Show more

We tested several hypotheses of disease pathology and of their putative molecular impact, including changes in single genes, the existence of subgroups of patients or disease subtypes, or the possibility of common biological pathways being affected in the disease process. Within the analytical limits of this relatively large genomic study, we found no evidence for molecular differences that correlated with depression and suicide, suggesting a pathology that is below the detection level of current genomic approaches, or that is either localized to other brain areas, or more associated with post-transcriptional effects and/or changes in protein levels or functions, rather than altered transcriptome in the prefrontal cortex. Show less

In this study, we have demonstrated the use of sex genes as true biological internal controls for genomic analysis of complex tissues, and suggested analytical guidelines for testing alternate oligonucleotide microarray data extraction protocols and for adjusting multiple statistical analysis of differentially expressed genes. Our results also provided evidence for sex differences in gene expression in the brain prefrontal cortex, supporting the notion of a putative direct role of… Show more

In this study, we have demonstrated the use of sex genes as true biological internal controls for genomic analysis of complex tissues, and suggested analytical guidelines for testing alternate oligonucleotide microarray data extraction protocols and for adjusting multiple statistical analysis of differentially expressed genes. Our results also provided evidence for sex differences in gene expression in the brain prefrontal cortex, supporting the notion of a putative direct role of sex-chromosome genes in differentiation and maintenance of sexual dimorphism of the central nervous system. Importantly, these analytical approaches are applicable to all microarray studies that include male and female human and animal subjects. Show less

Our Study indicates that the expression level of functional beta 2 adrenergic receptors (β2-ARs) modulates Fas-regulated liver apoptosis and that this apoptosis can be inhibited in vivo by giving β2-AR agonists. This may well form the basis for a new therapeutic approach to diseases involving abnormal apoptosis.

We have developed a transgenic mouse strain (F28) carrying the human beta 2-adrenoceptor (B2-AR) gene with its natural promoter region with the aim of producing a model that more closely reproduces the natural human B2-AR tissue expression pattern. We have obtained evidence that (a) the human B2-AR's structural gene is transcribed in several tissues of F28 mice; (b) the tissue distribution pattern of human B2-AR mRNA in F28 mice completely differs from that of mouse B2-AR mRNA; and (c) the… Show more

We have developed a transgenic mouse strain (F28) carrying the human beta 2-adrenoceptor (B2-AR) gene with its natural promoter region with the aim of producing a model that more closely reproduces the natural human B2-AR tissue expression pattern. We have obtained evidence that (a) the human B2-AR's structural gene is transcribed in several tissues of F28 mice; (b) the tissue distribution pattern of human B2-AR mRNA in F28 mice completely differs from that of mouse B2-AR mRNA; and (c) the tissue distribution pattern of mouse B2-AR mRNA in F28 mice is very similar to that observed in their non-transgenic littermates. We report that like humans, F28 mice express human B2-AR mRNA in liver, lung, brain, heart, and muscle. However, unlike humans, F28 mice do not accumulate human B2-AR mRNA in kidney and spleen. The number of B2-ARs increased slightly over the control values in muscle, heart, brain, and lung of F28 mice, while in liver these receptors were strongly overexpressed. We further showed that transgene beta 2-adrenoceptors couple to GTP-binding proteins, mediate B-AR agonist-stimulated adenylyl cyclase activation, and cause a strong enhancement of this response in liver membranes of F28 versus control mice. Finally, F28 mice show a phenotype of depressed ponderal development and perturbed hindquarter movements. This unique model should be useful to further investigate B2-AR causal relationships with human pathologies. Show less