Vesicular Zinc Modulates Cell Proliferation and Survival in the Developing Hippocampus.

In the brain, vesicular zinc, which refers to a subset of zinc that is sequestered into synaptic vesicles by zinc transporter 3 (ZnT3), has extensive effects on neuronal signalling and modulation. Vesicular zinc-focused research has mainly been directed to its role in the hippocampus, particularly in adult neurogenesis. However, whether vesicular zinc is involved in modulating neurogenesis during the early postnatal period has been less studied.

Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice.

Zinc is important in neural and synaptic development and neuronal transmission. Within the brain, zinc transporter 3 (ZnT3) is essential for zinc uptake into vesicles. Loss of vesicular zinc has been shown to produce neurodevelopmental disorder (NDD)-like behavior, such as decreased social interaction and increased anxiety- and repetitive-like behavior.

Examination of Zinc in the Circadian System.

Zinc is a trace element that is essential for a large number of biological and biochemical processes in the body. In the nervous system zinc is packaged into synaptic vesicles by the ZnT3 transporter, and synaptic release of zinc can influence the activity of postsynaptic cells, either directly through its own cognate receptors, or indirectly by modulating activation of receptors for other neurotransmitters. Here, we explore the anatomical and functional aspects of zinc in the circadian system.

Effects of social defeat stress and fluoxetine treatment on neurogenesis and behavior in mice that lack zinc transporter 3 (ZnT3) and vesicular zinc.

Depression is a leading cause of disability worldwide, in part because the available treatments are inadequate and do not work for many people. The neurobiology of depression, and the mechanism of action of common antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs), is not well understood. One mechanism thought to underlie the effects of these drugs is upregulation of adult hippocampal neurogenesis.

Brain-derived Neurotrophic Factor and TrkB Levels in Mice that Lack Vesicular Zinc: Effects of Age and Sex.

In certain neurons, zinc ions are stored in synaptic vesicles by zinc transporter 3 (ZnT3). Vesicular zinc can then be released synaptically to modulate myriad targets. In vitro evidence indicates that these targets may include brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB).

Effects of enriched housing on the neuronal morphology of mice that lack zinc transporter 3 (ZnT3) and vesicular zinc.

In the central nervous system, certain neurons store zinc within the synaptic vesicles of their axon terminals. This vesicular zinc can then be released in an activity-dependent fashion as an intercellular signal. The functions of vesicular zinc are not entirely understood, but evidence suggests that it is important for some forms of experience-dependent plasticity in the brain.

Elimination of vesicular zinc alters the behavioural and neuroanatomical effects of social defeat stress in mice.

Chronic stress can have deleterious effects on mental health, increasing the risk of developing depression or anxiety. But not all individuals are equally affected by stress; some are susceptible while others are more resilient. Understanding the mechanisms that lead to these differing outcomes has been a focus of considerable research.

Behavior of Adult 5-HT1 Receptor Knockout Mice Exposed to Stress During Prenatal Development.

Chronic maternal stress during pregnancy can have long-term, detrimental consequences for the offspring. An understanding of the mechanisms responsible for mediating these effects is essential for devising therapeutic interventions. Here, we examined whether serotonin 1A receptor (5-HTR) mediates the effects of maternal stress on the behavioral outcomes of the offspring as adults.

Signaling by Synaptic Zinc is Required for Whisker-Mediated, Fine Texture Discrimination.

Zinc-containing terminals are found throughout the neocortex, concentrated predominantly in layers II/III, V, and VI. Synaptic zinc is a potent neurotransmitter/modulator and, therefore, may mediate inter- or intra-cortical integration of sensory information. We have previously shown that levels of synaptic zinc are rapidly modulated in somatosensory (barrel) cortex, in an experience- and activity-dependent manner.

A new role for zinc in the brain.

Certain neurons in the auditory cortex release zinc to influence how the brain processes sounds.

Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function.

Zinc transporter 3 (ZnT3) is the sole mechanism responsible for concentrating zinc ions within synaptic vesicles in a subset of the brain's glutamatergic neurons. This vesicular zinc can then be released into the synaptic cleft in an activity-dependent fashion, where it can exert many signaling functions. This review provides a comprehensive discussion of the localization and function of ZnT3 and vesicular zinc in the central nervous system.

and together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex.

A derepression mode of cell-fate specification involving the transcriptional repressors Tbr1, Fezf2, Satb2, and Ctip2 operates in neocortical projection neurons to specify six layer identities in sequence. Less well understood is how laminar fate transitions are regulated in cortical progenitors. The proneural genes and cooperate in progenitors to control the temporal switch from neurogenesis to gliogenesis.

Behavioural outcomes of adult female offspring following maternal stress and perinatal fluoxetine exposure.

Unlabelled: Depression, anxiety, and stress are common in pregnant women. One of the primary pharmacological treatments for anxiety and depression is the antidepressant fluoxetine (Flx). Maternal stress, depression, and Flx exposure are known to effect neurodevelopment of the offspring, however, their combined effects have been scarcely studied, especially in female offspring.

Circadian behavior of adult mice exposed to stress and fluoxetine during development.

Introduction: Women of child-bearing age are the population at greatest risk for depression. The stress experienced during pregnancy and the associated antidepressant treatments can both affect fetal development. Fluoxetine (FLX) is among the most common antidepressants used by pregnant women.

Behavioral characterization of female zinc transporter 3 (ZnT3) knockout mice.

Zinc is an important element in all cells of the body, having structural, enzymatic, and regulatory functions. In some neurons, zinc is loaded into synaptic vesicles by zinc transporter 3 (ZnT3) and released into the synaptic cleft, where it can modulate neuronal function. ZnT3 knockout (KO) mice lack ZnT3 and thus lack synaptic zinc.

Prediction of treatment discontinuation and recovery from Borderline Personality Disorder: Results from an RCT comparing Schema Therapy and Transference Focused Psychotherapy.

Knowing what predicts discontinuation or success of psychotherapies for Borderline Personality Disorder (BPD) is important to improve treatments. Many variables have been reported in the literature, but replication is needed and investigating what therapy process underlies the findings is necessary to understand why variables predict outcome. Using data of an RCT comparing Schema Therapy and Transference Focused Psychotherapy as treatments for BPD, variables derived from the literature were tested as predictors of discontinuation and treatment success.

Predictors of caregiver depression and family functioning after perinatal stroke.

Background: Perinatal stroke is a leading cause of cerebral palsy and lifelong neurological morbidity. Studies on perinatal stroke outcomes are increasing, although examinations of its broader impact on parents and families have been limited. A recent study found that parents of children with moderate and severe outcomes have increased risk for psychosocial concerns, including depressive symptoms and poor family functioning.

The effects of chronic fluoxetine treatment following injury of medial frontal cortex in mice.

Injury of the brain is a leading cause of long-term disability. Recent evidence indicates that the selective serotonin reuptake inhibitor drug fluoxetine may be beneficial when administered following brain injury. However, its potential to promote recovery and the mechanisms by which it might do so require further characterization.

Mice lacking the transcription factor SHOX2 display impaired cerebellar development and deficits in motor coordination.

Purkinje cells of the developing cerebellum secrete the morphogen sonic hedgehog (SHH), which is required to maintain the proliferative state of granule cell precursors (GCPs) prior to their differentiation and migration to form the internal granule layer (IGL). Despite a wealth of knowledge regarding the function of SHH during cerebellar development, the upstream regulators of Shh expression during this process remain largely unknown. Here we report that the murine short stature homeobox 2 (Shox2) gene is required for normal Shh expression in dorsal-residing Purkinje cells.

Effects of lighting condition on circadian behavior in 5-HT1A receptor knockout mice.

Serotonin (5-HT) is an important regulator of the mammalian circadian system, and has been implicated in modulating entrained and free-running rhythms, as well as photic and non-photic phase shifting. In general, 5-HT appears to oppose the actions of light on the circadian system of nocturnal rodents. As well, 5-HT mediates, at least in part, some non-photic responses.

Increased aggression, improved spatial memory, and reduced anxiety-like behaviour in adult male mice exposed to fluoxetine early in life.

Rationale: Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective serotonin reuptake inhibitor, is prescribed for the treatment of depression in pregnant women; however, this commonly prescribed medication could affect fetal brain development as Flx crosses the placenta. The available data concerning the anatomical and behavioural consequences of perinatal exposure to Flx during early development on adult behaviour are limited and often contradictory.

Objectives: To further delineate the long-term behavioural effects of altering 5-HT during development, we examined the effects of perinatal Flx exposure on the behaviour of male mice as adults.

Parent and family impact of raising a child with perinatal stroke.

Background: Perinatal stroke is a leading cause of early brain injury, cerebral palsy, and lifelong neurological morbidity. No study to date has examined the impact of raising a child with perinatal stroke on parents and families. However, a large breadth of research suggests that parents, especially mothers, may be at increased risk for psychological concerns.

Survival of adult generated hippocampal neurons is altered in circadian arrhythmic mice.

The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well.

Long-term outcomes of developmental exposure to fluoxetine: a review of the animal literature.

During and following pregnancy, women are at high risk of experiencing depression, for which fluoxetine (FLX; brand names Prozac, Sarafem, Rapiflux) is the most commonly prescribed treatment. An estimated 1.4-2.