Biomedical subjects

Carol F Elias

Publications and source records attributed to Carol F Elias.

8 recordsLinked to original sources

PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗

PubMed2006

Neuropeptide glutamic acid-isoleucine may induce luteinizing hormone secretion via multiple pathways.

Neuropeptide glutamic acid-isoleucine (NEI) is a 14-amino acid peptide processed from prepro-melanin-concentrating hormone (ppMCH). In males, the localization of NEI is almost identical to that of MCH, the cell bodies of both being located primarily in the lateral hypothalamic area and zona incerta, projecting fibers throughout the brain. Although MCH has been widely studied, the role that NEI plays in brain circuitry has been poorly investigated. Recently, we showed that intracerebroventricular injection of NEI increases serum luteinizing hormone (LH) levels. In order to identify the anatomical substrate underlying this effect, we used combined immunohistochemistry methods to analyze the forebrains of females on the diestrus and proestrus days, as well as those of ovariectomized females treated with estradiol benzoate, with estradiol benzoate plus progesterone or with sesame oil (control animals). We found that ovariectomized females with no steroid treatment showed an increased number of NEI-immunoreactive neurons in the medial zona incerta. In addition, we observed dense to moderate NEI innervation of areas related to reproduction, including the organum vasculosum of the lamina terminalis, the anteroventral periventricular nucleus (AVPV) and the median eminence. The NEI fibers were in close apposition with the AVPV and gonadotropin-releasing hormone (GnRH) neurons expressing Fos in the afternoon of the proestrus day or following administration of estradiol benzoate plus progesterone. In the median eminence, NEI varicosities and terminal-like structures were in close proximity to blood vessels and GnRH fibers. Our results suggest that NEI might induce LH secretion in one of the following ways: by direct release into the median eminence, by modulation of GnRH neurons located in the preoptic area, by modulation of the GnRH terminals located in the median eminence or by an additive effect involving other neurotransmitters or neurohormones. Release of NEI might also induce LH secretion indirectly by modulating AVPV neurons.

Animals↗

PubMed2006

Female odors stimulate CART neurons in the ventral premammillary nucleus of male rats.

Olfactory information is known to influence both male and female sexual behavior. Chemosensory compounds known as pheromones activate distinct brain pathways, inducing innate and stereotyped behaviors, as well as hormonal changes. Studies have shown that female odors induce Fos expression in various brain nuclei of conspecific males, including the ventral premammillary nucleus (PMV). Although poorly investigated, previous studies have suggested that the PMV plays a role in aggressive and sexual behavior. In this study, we used Fos protein expression as a marker for neurons responsive to female odors in sexual inexperienced male rats exposed to soiled bedding. We observed that female odors induced intense Fos immunoreactivity throughout the PMV. Most of these neurons also express cocaine- and amphetamine-regulated transcript (CART) immunoreactivity. In addition, we used in situ hybridization and observed that, following exposure to female odors, CART mRNA increased only in the ventral PMV. Our results suggest that female odors stimulate CART production in the PMV of inexperienced males. Considering that the PMV CART neurons also express the leptin receptor, as well as the fact that they project to areas related to reproduction, we hypothesize that PMV CART neurons integrate nutritional and environmental (olfactory) information, being apt to modulate male reproductive behavior.

Animals↗

PubMed2005

Leptin fragments induce Fos immunoreactivity in rat hypothalamus.

Leptin presents an important role in energy balance and neuroendocrine control in mammals. In an attempt to identify regions of the leptin molecule responsible for its bioactivity, we have synthesized six peptides based on the protein three-dimensional structure. Fragments were synthesized by the solid-phase methodology, purified by reverse-phase high-performance liquid chromatography (RP-HPLC), and characterized by liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS). They were injected intravenously and their ability to induce Fos immunoreactivity (Fos-ir) in rat hypothalamus was compared with that of the recombinant human leptin and saline. Fragment Ac-[Ser117]Lep116-140-NH2 (V) induced Fos-ir in hypothalamic nuclei that express leptin receptor long form. No similar ability was observed for the other five fragments. To investigate whether Fos-ir was induced in the same neuronal group activated by leptin, we proceeded with a dual-label immunohistochemistry for cocaine- and amphetamine-regulated transcript (CART), a neuropeptide related to leptin action in rat hypothalamus. We found that Ac-[Ser117]Lep116-140-NH2 (V) differentially activates CART neurons through the rostrocaudal extension of the arcuate nucleus. These results suggest that this fragment acts in the same group of neurons that mediate leptin response. This approach may offer the basis for the development of leptin-related compounds, having potential application in human or veterinary medicine.

Animals↗

PubMed2005

Teneurin proteins possess a carboxy terminal sequence with neuromodulatory activity.

We have previously shown that a bioactive neuropeptide-like sequence is present at the carboxy-terminus of the teneurin transmembrane proteins. We have subsequently called this peptide 'teneurin C-terminal associated peptide' (TCAP). The sequence encodes a peptide 40 or 41 amino acids long flanked by a cleavage motif on the amino terminus and an amidation motif on the carboxy terminus, characteristic of bioactive peptides. This sequence is highly conserved in all vertebrates. A TCAP-like sequence is encoded by each of the four teneurin genes. We have therefore examined the neurological role TCAP-1 may play in mice and rats. In situ hybridization studies showed that the teneurin-1 mRNA containing the TCAP-1 sequence is expressed in regions of the forebrain and limbic system regulating stress and anxiety. A synthetic version of amidated mouse/rat TCAP-1 was prepared by solid-phase synthesis and used to investigate the in vitro and in vivo activity. TCAP-1 induces a dose-dependent change in cAMP accumulation and MTT activity in immortalized mouse neurons. Administration of synthetic TCAP-1 into the basolateral amygdala significantly increases the acoustic startle response in low-anxiety rats and decreases the response in high-anxiety animals in a dose-dependent manner. When 30 pmol TCAP-1 is administered into the lateral ventricles each day for 5 days, the sensitization of the rats to the acoustic startle response is abolished. These data indicate that TCAP may possess functions that are independent of the teneurin proprotein and together, the teneurins and TCAP, may represent a novel system to regulate neuronal function and emotionality.

Amino Acid Sequence↗

PubMed2004

Ciliary neurotrophic factor and leptin induce distinct patterns of immediate early gene expression in the brain.

Ciliary neurotrophic factor (CNTF) and leptin decrease food intake and body weight. Lipopolysaccharide (LPS) is a potent exogenous pyrogen and produces anorexia via cytokine production. CNTF-, leptin-, and LPS-induced cytokines all act on type I cytokine receptors. However, it is not known if these cytokines engage similar central nervous system (CNS) pathways to exert their effects. To assess mechanisms by which these cytokines act, we examined the patterns of immediate early gene expression (SOCS-3, c-fos, and tis-11) in the brain following intravenous administration. CNTF and LPS induced gene expression in circumventricular organs; ependymal cells of the ventricles, meninges, and choroid plexus; and the arcuate nucleus of the hypothalamus. CNTF administration also induced fever and cyclooxygenase-2 mRNA expression. In contrast, we found no evidence of leptin-induced inflammation. CNTF and leptin are being assessed as potential therapeutic anti-obesity agents, and both potently reduce food intake. Our findings support the hypothesis that CNTF and leptin engage distinct CNS sites and CNTF possesses inflammatory properties distinct from leptin.

Animals↗

PubMed2003

Urocortin in the central nervous system of a primate (Cebus apella): sequencing, immunohistochemical, and hybridization histochemical characterization.

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. Of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

Amino Acid Sequence↗

PubMed2003

Dopamine and melanin-concentrating hormone neurons are distinct populations in the rat rostromedial zona incerta.

Zona incerta (ZI) is a controversial diencephalic area with a variety of cytoarchitectonic subdivisions, neurotransmitters and related functions. Medial ZI synthesizes dopamine (A13 group) and tyrosine hydroxylase (TH, a catecholamine synthesizing enzyme), which has been considered a neurochemical marker for this region. The rostromedial ZI also expresses melanin-concentrating hormone (MCH), but it is not known whether dopamine and MCH are colocalized. By using double label immunohistochemistry we analyzed the distribution of TH and MCH in the rat ZI. We found that MCH and TH neurons are intermingled but are not colocalized.

Animals↗