Maintenance of optogenetic channel rhodopsin (ChR2) function in aging mice: Implications for pharmacological studies of inhibitory synaptic transmission, quantal content, and calcium homeostasis.

Disruption of synaptic function is believed to represent a common pathway contributing to cognitive decline during aging. Optogenetics is a prodigious tool for studying relationships between function and synaptic circuitry but models utilizing viral vectors present limitations. Careful characterization of the functionality of channel rhodopsin in transgenic models is crucial for determining whether they can be used across aging.

Peripheral immune challenges elicit differential up-regulation of hippocampal cytokine and chemokine mRNA expression in a mouse model of the 15q13.3 microdeletion syndrome.

The human heterozygous 15q13.3 microdeletion is associated with neuropathological disorders, most prominently with epilepsy and intellectual disability. The 1.

Molecular, physiological and behavioral characterization of the heterozygous Df[h15q13]/+ mouse model associated with the human 15q13.3 microdeletion syndrome.

The human 15q13.3 microdeletion syndrome (DS) is caused by a heterozygous microdeletion (MD) affecting six genes: FAN1; MTMR10; TRPM1; KLF13; OTUD7A; and CHRNA7. Carriers are at risk for intellectual disability, epilepsy, autism spectrum disorder, and schizophrenia.

Central and peripheral immune responses to low-dose lipopolysaccharide in a mouse model of the 15q13.3 microdeletion.

Carriers of the human 15q13.3 microdeletion (MD) present with a variable spectrum of neuropathological phenotypes that range from asymptomatic to severe clinical outcomes, suggesting an interplay of genetic and non-genetic factors. The most common 2 MB 15q13.

Distribution of α7 Nicotinic Acetylcholine Receptor Subunit mRNA in the Developing Mouse.

Homomeric α7 nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in the central and peripheral nervous system (CNS and PNS, respectively), and spinal cord. In addition, expression and functional responses have been reported in non-neuronal tissue. In the nervous system, α7 nAChR subunit expression appears early during embryonic development and is often transiently upregulated, but little is known about their prenatal expression outside of the nervous system.

Activation of immediate early genes by nicotine after chronic neonatal nicotine exposure in brain areas involved in stress and anxiety responses.

Maternal smoking has negative long-term consequences on affective behaviors, and in rodents, chronic neonatal nicotine exposure (CNN) results in increased anxiety. In rat pups, acute nicotine stimulation activates brain regions associated with stress and anxiety, but chronic nicotine exposure could desensitize of nicotinic acetylcholine receptors, the molecular target of nicotine. Here, we determined whether CNN affected neuronal activation by an acute nicotine challenge.

Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain.

The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe.

Neonatal nicotine exposure increases excitatory synaptic transmission and attenuates nicotine-stimulated GABA release in the adult rat hippocampus.

Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1-7, a period that falls developmentally into the third human trimester.

New functional handle for use as a self-reporting contrast and delivery agent in nanomedicine.

The synthesis and photophysical characterization of a chromophore-bridged block copolymer system is presented. This system is based on a dithiomaleimide (DTM) functional group as a highly emissive functionality which can readily be incorporated into polymeric scaffolds. A key advantage of this new reporter group is its versatile chemistry, ease of further functionalization, and notably small size, which allows for ready incorporation without affecting or disrupting the self-assembly process critical to the formation of core-shell polymeric contrast and drug delivery agents.

Varenicline and nicotine enhance GABAergic synaptic transmission in rat CA1 hippocampal and medial septum/diagonal band neurons.

Aims: The FDA approved smoking cessation aid varenicline can effectively attenuate nicotine-stimulated dopamine release. Varenicline may also exert important actions on other transmitter systems that also influence nicotine reinforcement or contribute to the drug's cognitive and affective side effects. In this study, we determined if varenicline, like nicotine, can stimulate presynaptic GABA release.

Neuregulin and dopamine modulation of hippocampal gamma oscillations is dependent on dopamine D4 receptors.

The neuregulin/ErbB signaling network is genetically associated with schizophrenia and modulates hippocampal γ oscillations--a type of neuronal network activity important for higher brain processes and altered in psychiatric disorders. Because neuregulin-1 (NRG-1) dramatically increases extracellular dopamine levels in the hippocampus, we investigated the relationship between NRG/ErbB and dopamine signaling in hippocampal γ oscillations. Using agonists for different D1- and D2-type dopamine receptors, we found that the D4 receptor (D4R) agonist PD168077, but not D1/D5 and D2/D3 agonists, increases γ oscillation power, and its effect is blocked by the highly specific D4R antagonist L-745,870.

Opposing actions of ethanol and nicotine on microRNAs are mediated by nicotinic acetylcholine receptors in fetal cerebral cortical-derived neural progenitor cells.

Background: Ethanol (EtOH) and nicotine are often co-abused. However, their combined effects on fetal neural development, particularly on fetal neural stem cells (NSCs), which generate most neurons of the adult brain during the second trimester of pregnancy, are poorly understood. We previously showed that EtOH influenced NSC maturation in part, by suppressing the expression of specific microRNAs (miRNAs).

Smoking during pregnancy: lessons learned from epidemiological studies and experimental studies using animal models.

Numerous epidemiological studies in the human population clearly indicate that smoking while pregnant has deleterious effects on fetal development as well as long-term adverse consequences on postnatal development and maturation of several organ systems. Low birth weight, sudden infant death syndrome (SIDS), behavioral disorders including attention deficit hyperactivity disorder (ADHD), externalizing and internalizing behavioral problems and conduct disorders in children have all been linked to prenatal exposure to tobacco smoke. The major pharmacologically active chemical found in tobacco smoke is nicotine, and prenatal exposure to nicotine has been shown to have significant effect on the development of multiple organ systems, including the nervous, respiratory, and cardiovascular systems.

Effects of developmental nicotine exposure in rats on decision-making in adulthood.

Exposure to tobacco smoke during pregnancy is associated with a range of adverse outcomes in offspring, including cognitive deficits and increased incidence of attention deficit-hyperactivity disorder, but there is a considerable controversy with regard to the causal role of tobacco smoke in these outcomes. To determine whether developmental exposure to the primary psychoactive ingredient in tobacco smoke, nicotine, may cause long-lasting behavioral alterations analogous to those in attention deficit-hyperactivity disorder, male Sprague-Dawley rats underwent a chronic neonatal nicotine administration regimen, which models third-trimester human exposure. Male rat pups were administered nicotine (6 mg/kg/day) by oral gastric intubation on postnatal days 1-7.

Chronic neonatal nicotine exposure increases excitation in the young adult rat hippocampus in a sex-dependent manner.

Smoking during pregnancy exposes the fetus to nicotine, resulting in nicotine-stimulated neurotransmitter release. Recent evidence suggests that the hippocampus develops differently in males and females with delayed maturation in males. We show that chronic nicotine exposure during the first postnatal week has sex-specific long-term effects.

Signal intensities of radiolabeled cRNA probes used alone or in combination with non-isotopic in situ hybridization histochemistry.

This study addressed the question of whether radioactive hybridization signal intensities are reduced in combined isotopic and non-isotopic double in situ hybridization (DISH) compared with those in single in situ hybridization (ISH). Non-isotopic digoxigenin (Dig)-labeled hybrids were detected using an alkaline phosphatase (AP) enzymatic reaction which results in nitroblue tetrazolium chloride (NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP)-salt precipitation that could shield S35-radiation from penetrating to the surface. Sections were plastic coated of with 2% parlodion to prevent a chemical reaction between AP and developer during processing of the photosensitive emulsion, which could further reduce radioactive hybridization signal detection by autoradiography.

Chronic neonatal nicotine exposure increases mRNA expression of neurotrophic factors in the postnatal rat hippocampus.

Nicotine, the psychoactive ingredient in tobacco, can be neuroprotective but the mechanism is unknown. In the adult hippocampus, chronic nicotine can increase expression of growth factors which could contribute to nicotine's neuroprotective effects. During development, nicotine could also increase expression of neurotrophic factors.

Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs in rat hippocampal GABAergic interneurons.

Hippocampal inhibitory interneurons are a diverse population of cells widely scattered in the hippocampus, where they regulate hippocampal circuit activity. The hippocampus receives cholinergic projections from the basal forebrain, and functional studies have suggested the presence of different subtypes of nicotinic acetylcholine receptors (AChRs) on gamma-aminobutyric acid (GABA)ergic interneurons. Single-cell polymerase chain reaction analysis had confirmed that several nAChR subunit mRNAs are co-expressed with glutamate decarboxylase 67 (GAD67), the marker for GABAergic interneurons.

Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects.

Long-term consequences of maternal smoking and developmental chronic nicotine exposure.

Every year, a large number of children are exposed to smoking during pregnancy which increases the risk of decreased birth weight, fetal morbidity and behavioral abnormalities. Therefore, nicotine replacement therapy (NRT) is often considered as a treatment option. Despite a large number of epidemiological studies, there are conflicting reports about the long-term consequences of maternal smoking on cognitive function, attention deficit hyperactivity disorder (ADHD) and other behavioral abnormalities.

Postnatal expression of alpha2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels composed of alpha and beta subunits. nAChR subunit expression is highly regulated during development. Previous studies have revealed increased expression of alpha3, alpha5, alpha7, and beta4 subunit mRNAs and alpha7 binding sites during hippocampal and cortical development.

Effects of paraformaldehyde fixation on nicotinic acetylcholine receptor binding in adult and developing rat brain sections.

In vitro receptor autoradiography requires unfixed tissue sections, but incubation and washing procedures often result in substantial tissue damage in sections from developing brain, hindering quantitative and qualitative analysis. Formaldehyde fixation greatly preserves morphology. However, fixation can interfere with pharmacological properties of receptors, increase in non-specific background labeling, or even destroy ligand binding sites.

Chronic nicotine induces growth retardation in neonatal rat pups.

In the United State, 20% of pregnant women smoke. One of the most consistent adverse outcomes is reduced birth weight in the off-spring. Animal studies using chronic nicotine, the major psychoactive tobacco ingredient, have shown conflicting results, questioning the role of nicotine in growth retardation.

Expression of alpha5 nicotinic acetylcholine receptor subunit mRNA during hippocampal and cortical development.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated pentameric cation channels of alpha and beta subunits. The alpha5 subunit, when added to heteromeric complexes, alters pharmacological and physiological properties of nAChRs, which may be important during development. Here we have evaluated the pre- and postnatal expression of alpha5 subunit mRNA in rat cortex and hippocampus using highly sensitive in situ hybridization.

Expression of opioid peptides and receptors in striatum and substantia nigra during rat brain development.

We have used highly sensitive in situ hybridization to determine opioid receptor and peptide expression in embryonic and postnatal rat striatum, to follow the compartmentalization into patch and matrix structures, and have examined their developmental expression in the dopaminergic cell group of the substantia nigra (SN). Furthermore, opioid receptor binding sites were characterized in adjacent sections using highly selective ligands for the opioid receptor subtypes. The major findings of the study are: (1) striatal patches were first delineated by prodynorphin mRNA followed by mu opioid receptor mRNA expression at embryonic days 19 and 21, respectively; (2) in neonates, prodynorphin, mu and kappa opioid receptor mRNAs were transiently co-distributed within patches; (3) prodynorphin mRNA was co-expressed with mu but not kappa, receptor mRNA in neonatal patch neurons; (4) in the SN, kappa receptor and prodynorphin mRNAs were detected as early as embryonic days 15 and 19, respectively; (5) kappa receptor, but not prodynorphin, mRNA was expressed in dopaminergic neurons in the SN.