From smooth brains to rocky mountains: Quentin Pittman in a Quintessentially Canadian career.

This commentary is to honour Dr Quentin Pittman as he steps back from an active role in academia. Pittman's work leaves a legacy of ground-breaking discoveries, impeccable research, and generous mentorship. His work on thermoregulation, vasopressin, perinatal programming, and hypothalamic function laid a good part of the foundation of the psychoneuroimmunology research we do today.

Maternal immune activation alters the GABAergic system in the prefrontal cortex of female rat offspring: Role of interleukin-6.

Maternal immune activation (MIA) induces long-term cognitive impairments by modulating the gamma-aminobutyric acid (GABA)ergic system. Experimental evidence suggests that maternal immune challenge with bacterial active ingredient lipopolysaccharide (LPS) reduces GABAergic tone in the offspring's prefrontal cortex. In this study, we aimed to assess whether interleukin-6 (IL-6) contributes to this reduced GABAergic system in the prefrontal cortex of juvenile offspring.

The Effects of Neuroactive Steroids on Myelin in Health and Disease.

Myelin plays a pivotal role in the efficient transmission of nerve impulses. Disruptions in myelin integrity are associated with numerous neurological disorders, including multiple sclerosis. In the central nervous system (CNS), myelin is formed by oligodendrocytes.

Breastfeeding promotes oligodendrocyte precursor cells division and myelination in the demyelinated corpus callosum.

Demyelination alters the conduction of neuronal signals and hampers sensory-motor functions. Experimental and clinical evidence suggest that breastfeeding exerts a promyelinating impact on the maternal brain. The mechanism underlying this neuroprotective effect is not well-understood.

Astrocytes and Microglia in Stress-Induced Neuroinflammation: The African Perspective.

Africa is laden with a youthful population, vast mineral resources and rich fauna. However, decades of unfortunate historical, sociocultural and leadership challenges make the continent a hotspot for poverty, indoor and outdoor pollutants with attendant stress factors such as violence, malnutrition, infectious outbreaks and psychological perturbations. The burden of these stressors initiate neuroinflammatory responses but the pattern and mechanisms of glial activation in these scenarios are yet to be properly elucidated.

Muscle Hypertrophy in a Newly Developed Resistance Exercise Model for Rats.

Clinical evidence suggests that resistance exercise exerts health benefit. The mechanisms underlying such health benefits is largely explored in experimental animals. Available experimental models have several shortcomings such as the need for noxious stimuli that could affect the physiological readouts.

Prenatal Activation of Glucocorticoid Receptors Induces Memory Impairment in a Sex-Dependent Manner: Role of Cyclooxygenase-2.

Prenatal exposure to dexamethasone (DEX) results in long-lasting effects on cognitive functions such as learning and memory impairment. However, the mechanisms underlying these DEX-induced deleterious effects are not well known. Here, we assessed whether cyclooxygenase-2 (COX-2) is involved in the impact of prenatal exposure to DEX on learning and memory during adulthood.

Progesterone partially recovers placental glucose transporters in dexamethasone-induced intrauterine growth restriction.

Research Question: How does progesterone improve fetal outcome and change the expression of placental glucose transporters (GLUT) in dexamethasone-induced intrauterine growth restriction (IUGR)?

Design: A total of 64 rats were divided randomly into four different treatment groups based on daily i.p. injections of either saline or dexamethasone in the presence or absence of progesterone.

Maternal Interleukin-6 Hampers Hippocampal Neurogenesis in Adult Rat Offspring in a Sex-Dependent Manner.

Maternal immune activation (MIA) during pregnancy leads to long-lasting effects on brain development and function. Several lines of evidence suggest that the maternal inflammatory cytokine interleukin (IL)-6 plays a crucial role in the long-lasting effects of MIA on adult offspring. IL-6 is naturally produced during pregnancy in the absence of any underlying immune activation.

Differential Release of Exocytosis Marker Dyes Indicates Stimulation-Dependent Regulation of Synaptic Activity.

There is a general consensus that synaptic vesicular release by a full collapse process is the primary machinery of synaptic transmission. However, competing view suggests that synaptic vesicular release operates via a kiss-and-run mechanism. By monitoring the release dynamics of a synaptic vesicular marker, FM1-43 from individual synapses in hippocampal neurons, we found evidence that the release of synaptic vesicle was delayed by several seconds after the start of field stimulation.

Ganaxolone enhances microglial clearance activity and promotes remyelination in focal demyelination in the corpus callosum of ovariectomized rats.

Aim: Experimental studies have shown that the progesterone metabolite, allopregnanolone, is endowed with promyelinating effects. The mechanisms underlying these promyelinating effects are not well understood. Therefore, we explored the impact of allopregnanolone's synthetic analogue, ganaxolone, on remyelination and microglial activation following focal demyelination in the corpus callosum of ovariectomized rats.

Enhanced remyelination during late pregnancy: involvement of the GABAergic system.

Pregnant women with MS experience fewer relapses, especially during the third trimester. In this study, we explore the cellular and molecular events that bring about the protective effect of late pregnancy on the course of de/remyelination in rats. Using cellular, molecular, and ultrastructural methods, we explored remyelination in response to a focal demyelination in the corpus callosum of late pregnant, virgin, and postpartum rats.

Prenatal Inflammation Dampens Neurogenesis and Enhances Serotonin Transporter Expression in the Hippocampus of Adult Female Rats.

Background/aims: Prenatal exposure to lipopolysaccharide (LPS) dampens hippocampal neurogenesis. This effect is associated with increased anxiety-like behavior in adult offspring. Furthermore, blocking serotonin transporters (SERT) promotes adult neurogenesis.

Exposure to synthetic glucocorticoids during pregnancy alters the expression of p73 gene variants in fetal brains in a sex-specific manner.

Fetal exposure to dexamethasone (DEX) alters brain plasticity and cognitive functions during adulthood in a sex-dependent manner. The mechanisms underlying such long-lasting sex-dependent change of prenatal DEX is not well understood. The p73 gene plays an important role in brain development.

Impact of prenatal immune challenge on the demyelination injury during adulthood.

Aim: Brain inflammation is associated with several brain diseases such as multiple sclerosis (MS), a disease characterized by demyelination. Whether prenatal immune challenge affects demyelination-induced inflammation in the white matter during adulthood is unclear. In the present study, we used a well-established experimental model of focal demyelination to assess whether prenatal immune challenge affects demyelination-induced inflammation.

Androstenediol Reduces Demyelination-Induced Axonopathy in the Rat Corpus Callosum: Impact on Microglial Polarization.

: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum.

Dexamethasone-Induced Intrauterine Growth Restriction Is Associated With Altered Expressions of Metastasis Tumor Antigens and Cell Cycle Control Proteins in Rat Placentas.

Molecular mechanisms affecting placental formation in intrauterine growth-restricted (IUGR) pregnancies are not clearly understood. Since metastasis tumor antigens (MTAs) MTA1 and MTA2 promote cell proliferation and MTA3 suppresses it, we hypothesized that IUGR alters cell survival/cell death programs driven by placental MTAs. To induce IUGR, pregnant Sprague Dawley rats were given daily intraperitoneal injections of either saline or dexamethasone (0.

Demyelination-Induced Inflammation Attracts Newly Born Neurons to the White Matter.

There is compelling evidence that microglial activation negatively impacts neurogenesis. However, microglia have also been shown to promote recruitment of newly born neurons to injured areas of the gray matter. In the present study, we explored whether demyelination-triggered inflammation alters the process of neurogenesis in the white matter.

Prenatal Activation of Toll-Like Receptor-4 Dampens Adult Hippocampal Neurogenesis in An IL-6 Dependent Manner.

Prenatal immune challenge has been associated with alteration in brain development and plasticity that last into adulthood. We have previously shown that prenatal activation of toll-like receptor 4 by lipopolysaccharide (LPS) induces IL-6-dependent STAT-3 signaling pathway in the fetal brain. Whether this IL-6-dependent activation of fetal brain results in long lasting impact in brain plasticity is still unknown.

Toll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in the fetal brain: role of interleukin-6.

Background: Prenatal exposure to pathogens induces long lasting effect on brain function and plasticity. It is unclear how maternal immune stress impacts fetal brain development. Immune challenged pregnant rats induce the production of inflammatory cytokines including tumor necrosis factor (TNF)α, interleukin (IL)1β, and IL-6.

The promyelinating properties of androstenediol in gliotoxin-induced demyelination in rat corpus callosum.

Aims: Experimental evidence has shown that the adrenal steroid hormone, androstenediol, dampens the symptoms of demyelination. However, the cellular and molecular effects of androstenediol are not yet known. In the present study, we investigated the cellular and subcellular effects of this hormone in a gliotoxin-induced demyelination model.

TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal replacement therapy.

Experimental and epidemiological data show that the severity and the duration of brain inflammation are attenuated in females compared to males. This attenuated brain inflammation is ascribed to 17β-estradiol. However, several studies suggest that 17β-estradiol is also endowed with proinflammatory properties.

Long-lasting impact of early life immune stress on neuroimmune functions.

Fever is one major cardinal sign of disease. It results from an intricate interplay between the immune system and the central nervous system. Bacterial or viral infections activate peripheral immune competent organs which send inflammatory signals to the brain and lead to an increase in body temperature.

Glucocorticoid-induced fetal brain growth restriction is associated with p73 gene activation.

Fetal exposure to excessive amounts of glucocorticoids (GCs) hampers proper brain development. The molecular mechanism(s) underlying these GCs effects are not well understood. We explored the impact of fetal exposure to maternal GCs on fetal brain expression of p63 and p73 transactivation (TA) and dominant negative (ΔN) gene variants that promote neural cell death (TA) and cell survival programs (ΔN).