Anxiolytic reversal of classically conditioned / chronic stress-induced gene expression and learning in the Stress Alternatives Model.

Social decision-making is critically influenced by neurocircuitries that regulate stress responsiveness. Adaptive choices, therefore, are altered by stress-related neuromodulatory peptide systems, such as corticotropin releasing factor (CRF). Experimental designs that take advantage of ecologically salient fear-inducing stimuli allow for revelation of neural mechanisms that regulate the balance between pro- and anti-stress responsiveness.

Cleavage of proBDNF to BDNF by a tolloid-like metalloproteinase is required for acquisition of in vitro eyeblink classical conditioning.

The tolloid/bone morphogenetic protein-1 family of metalloproteinases have an important role in the regulation of embryonic pattern formation and tissue morphogenesis. Studies suggest that they participate in mechanisms of synaptic plasticity in adults, but very little is known about their function. Recently, we isolated a reptilian ortholog of the tolloid gene family designated turtle tolloid-like gene (tTll).

Activation of mammalian Tolloid-like 1 expression by hypoxia in human neuroblastoma SH-SY5Y cells.

Mammalian Tolloid-like 1 (mTll-1) is an astacin metalloprotease that is a member of the Tolloid family of proteins. mTll-1 cleaves chordin, an inhibitor of bone morphogenetic proteins (BMPs) and potentiates activity of the BMPs. Prenatal stress and glucocorticoids decrease mTll-1 expression whereas voluntary exercise increase mTll-1 gene expression in the mouse hippocampus.

Activation of Tolloid-like 1 gene expression by the cardiac specific homeobox gene Nkx2-5.

Mammalian Tolloid-like 1 (Tll-1) is a pleiotropic metalloprotease that is expressed by a small subset of cells within the precardiac mesoderm and is necessary for proper heart development. Following heart tube formation Tll-1 is expressed by the endocardium and regions of myocardium overlying the region of the muscular interventricular septum. Mutations in Tll-1 lead to embryonic lethality due to cardiac defects.

Seasonal variation of myostatin gene expression in pectoralis muscle of house sparrows (Passer domesticus) is consistent with a role in regulating thermogenic capacity and cold tolerance.

Winter acclimatization in small birds overwintering in cold climates, including house sparrows (Passer domesticus), is associated with improved cold tolerance, elevated summit metabolic rates (M(sum) = maximum cold-induced metabolic rate), and increased pectoralis muscle mass compared to summer birds. Myostatin is a potent autocrine/paracrine inhibitor of skeletal muscle growth in mammals and birds and is a potential candidate for regulation of seasonal phenotypic flexibility in birds. As a first step toward examining such a role for myostatin in small birds, we measured summer and winter gene expression of myostatin and its potential metalloproteinase activators TLL-1 and TLL-2 in house sparrows from southeastern South Dakota.

Characterization of a novel reptilian tolloid-like gene in the pond turtle, Pseudemys scripta elegans.

The Tolloid metalloproteases are pleiotropic enzymes that are important for many developmental processes. This study describes the isolation and characterization of a novel Tolloid family member from the pond turtle Pseudemys scripta elegans. The turtle Tolloid, designated tTll, is found in two forms.

Tolloid-like 1 is negatively regulated by stress and glucocorticoids.

Glucocorticoids affect a variety of tissues to enable the organism to adapt to the stress. Hippocampal neurons contain glucocorticoid receptors and respond to elevated glucocorticoid levels by down-regulating the HPA axis. Chronically, however, stress is deleterious to hippocampal neurons.

Abducens conditioning in in vitro turtle brain stem without cerebellum requires NMDA receptors and involves upregulation of GluR4-containing AMPA receptors.

Previous work showed that in vitro abducens eyeblink classical conditioning of turtle brain stem-cerebellum preparations involved NMDA-mediated mechanisms and redistribution of GluR4-containing AMPA receptors in the abducens motor nuclei. Since conditioning can be obtained in brain stem preparations without the cerebellum, we examined whether similar mechanisms were involved during conditioning of the brain stem alone. The results showed that conditioning could not be induced in the presence of the NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (AP-5) and that abducens nerve conditioned responses, once initiated in normal saline, were significantly attenuated in the presence of AP-5.

Role for calbindin-D28K in in vitro classical conditioning of abducens nerve responses in turtles.

Intracellular calcium has a pivotal role in synaptic modifications that may underlie learning and memory. The present study examined whether there were changes in immunoreactivity levels of the AMPA receptor subunits GluR2/3 and calcium binding proteins during classical conditioning recorded in the abducens nerve of in vitro brain stem preparations from turtles. The results showed that abducens motor neurons in unconditioned turtle brain stems were immunopositive for GluR2/3, calbindin-D28K, and calmodulin, but were immunonegative for parvalbumin.