Biomedical subjects

Jean-François Poulin

Publications and source records attributed to Jean-François Poulin.

6 recordsLinked to original sources

PubMed2006

Enkephalinergic afferents of the centromedial amygdala in the rat.

The connectivity of the amygdaloid complex has been extensively explored with both anterograde and retrograde tracers. Even though the afferents of the centromedial amygdala [comprising the central (CEA) and medial (MEA) amygdaloid nuclei] are well established, relatively little is known about the neuropeptide phenotype of these connections. In this study, we first examined the distribution of mu-opioid receptor (MOR) and delta-opioid receptor (DOR) in the amygdala via in situ hybridization and immunohistochemistry. We then investigated the distribution of Met-enkephalin (ENK) and Leu-ENK fibers with immunohistochemistry and examined the distribution of preproenkephalin mRNA in the amygdala by using in situ hybridization. Finally, we examined the ENK projections to the CEA and MEA by using stereotaxic injections of the retrograde tracer cholera toxin subunit B or fluorogold revealed by immunohistochemistry combined with in situ hybridization to identify ENKergic neurons. Our results indicate that the centromedial amygdala receives ENK afferents, as indicated by the presence of MOR, DOR, and ENK fibers in the CEA and MEA, originating primarily from the bed nucleus of the stria terminalis (BST) and from other amygdaloid nuclei. The posterior BST, the basomedial nucleus (BMA), and the cortical nucleus of the amygdala (COA) were found to be the major ENK afferents of the MEA, whereas the anterolateral BST, the COA, the MEA, and the BMA provided the main ENKergic innervation of the CEA. In addition, we found that the ventromedial nucleus of the hypothalamus and the pontine parabrachial nucleus provide a moderate ENK input to the CEA and MEA. The functional implications of these connections in stress, anxiety, and nociception are discussed.

Afferent Pathways↗

PubMed2006

Simultaneous separation of acid and basic bioactive peptides by electrodialysis with ultrafiltration membrane.

beta-Lactoglobulin (beta-lg), one of the major whey components, can release by enzymatic hydrolysis different bioactive peptidic sequences according to the enzyme used. However, these protein hydrolysates have to be fractionated to obtain peptides in a more purified form. The aim of the present work was to evaluate the feasibility of separating peptides from a beta-lg hydrolysate using an ultrafiltration (UF) membrane stacked in an electrodialysis (ED) cell and to study the effect of pH on the migration of basic/cationic and acid/anionic peptides in the ED configuration. Electrodialysis with ultrafiltration membrane (EDUF) appeared to be a selective method of separation since amongst a total of 40 peptides in the raw hydrolysate, only 13 were recovered in the separated adjacent solutions (KCl 1 and KCl 2). Amongst these 13 migrating peptides, 3 acid/anionic peptides migrated only in one compartment (KCl 1), while 3 basic/cationic peptides migrated only in the second compartment (KCl 2) and that whatever the pH conditions of the hydrolysate solution. Furthermore, the highest migration was obtained for the ACE-inhibitory peptide beta-lg 142-148, with a value of 10.75%. The integrity of the UF membrane was kept and EDUF would minimize the fouling of UF membrane.

Animals↗

PubMed2005

Cholecystokinin and endogenous opioid peptides: interactive influence on pain, cognition, and emotion.

It is well documented that stressful life experiences contribute to the etiology of human mood disorders. Cholecystokinin (CCK) is a neuropeptide found in high concentrations throughout the central nervous system, where it is involved in numerous physiological functions. A role for CCK in the induction and persistence of anxiety and major depression appears to be conspicuous. While increased CCK has been associated with motivational loss, anxiety and panic attacks, an increase in mesocorticolimbic opioid availability has been associated with coping and mood elevation. The close neuroanatomical distribution of CCK with opioid peptides in the limbic system suggests that there may be an opioid-CCK link in the modulation and expression of anxiety or stressor-related behaviors. In effect, while CCK induces relatively protracted behavioral disturbances in both animal and human subjects following stressor applications, opioid receptor activation may change the course of psychopathology. The antagonistic interaction of CCK and opioid peptides is evident in psychological disturbances as well as stress-induced analgesia. There appears to be an intricate balance between the memory-enhancing and anxiety-provoking effects of CCK on one hand, and the amnesic and anxiolytic effects of opioid peptides on the other hand. Potential anxiogenic and mnemonic influences of site-specific mesocorticolimbic CCK and opioid peptide availability, the relative contributions of specific CCK and opioid receptors, as well as the time course underlying neuronal substrates of long-term behavioral disturbances as a result of stressor manipulations, are discussed.

Animals↗

PubMed2005

Multiparameter evaluation of human thymic function: interpretations and caveats.

After the provision of highly active antiretroviral therapy (HAART), the level of circulating CD4+ T cells increases in many adults infected with the human immunodeficiency virus, type 1 (HIV). To study factors involved in immune reconstitution, we have measured thymic abundance by CT scans, circulating naive-phenotype CD4+ T cells by flow cytometry, and T cell receptor (TCR) rearrangement excision circles (TRECs) by quantitative PCR in 40 virologically suppressed, HIV-infected adults and 33 age-matched, HIV-uninfected controls. In HIV-uninfected subjects, naive T cell numbers, thymic abundance, and the frequency of circulating naive CD4+ T cells bearing TRECs decreased with age, as expected. When corrected for this relationship with age, naive T cell numbers correlated significantly with naive T cell TREC frequencies. Virologically suppressed HIV-infected subjects had higher TREC frequencies, and subjects over the age of 39 were more likely to have abundant thymus compared to age-matched, HIV-uninfected adults. Nevertheless, all HIV-infected subjects had reduced absolute numbers of naive T cells, irrespective of thymic size, age, or TREC frequencies. These data illustrate the complex relationship between these measures of thymic size and function and underscore the need to develop more definitive measures of thymic function in the future.

Adult↗

PubMed2004

HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation.

The supply of naive T cells by the thymus normally requires precursor T cell proliferation within the thymus and would be particularly important in the setting of HIV infection when both naive and memory T cells are progressively depleted. As a robust, quantitative index of intrathymic proliferation, the ratio of different T cell receptor excision circles (TRECs), molecular markers of distinct T cell receptor rearrangements occurring at different stages of thymocyte development, was measured in peripheral blood-mononuclear cells (PBMCs). This ratio has the virtue that it is a "signature" of thymic emigrants throughout their entire life and, thus, can be measured in peripheral cell populations that are easy to obtain. Using the new assay, we evaluated the effect of HIV infection on intrathymic precursor T cell proliferation by longitudinal analysis of PBMCs from recently infected individuals. Our findings reveal a substantial reduction in intrathymic proliferation. The analysis also indicates the existence of a compensatory mechanism acting to sustain the numbers of recent thymic emigrants (RTEs) in the periphery.

Aging↗

PubMed2003

Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease.

Allogeneic hematopoietic stem cell transplantation (AHSCT) leads to a prolonged state of immunodeficiency characterized by low peripheral naive T-cell counts. To identify the mechanisms leading to this defect we quantitatively and qualitatively analyzed thymic function through quantification of T-cell receptor excision circle (TREC) frequencies (both the signal-joint TREC [sjTREC] and 6 different DbetaJbeta TRECs, by-products of T-cell receptor [TCR] alpha and beta gene rearrangement, respectively), in conjunction with immunophenotype and spectratype analyses in a cohort of patients sampled from 1 to 10 years following AHSCT. In this cohort, reduced thymic function was associated only with ongoing clinical chronic graft-versus-host disease (cGVHD). Nonetheless, the diversity of thymic production remained unchanged irrespective of the patient's cGVHD status. Interestingly, increased homeostatic proliferation was found in the naive T-cell compartment of cGVHD- patients who underwent transplantation. However, reduced expression of both the interleukin-7 receptor alpha (IL-7Ralpha) (CD127) chain and the antiapoptotic protein Bcl-2 was observed. Taken together, these data indicate that the inability to reconstitute the naive T-cell compartment for several years after AHSCT, in the absence of cGVHD, is a consequence of impaired naive T-cell survival rather than thymic dysfunction.

Adult↗