Search results for "Prosencephalon"
showing 10 items of 25 documents
Lipoprotein receptor loss in forebrain radial glia results in neurological deficits and severe seizures.
2020
The Alzheimer disease-associated multifunctional low-density lipoprotein receptor-related protein-1 is expressed in the brain. Recent studies uncovered a role of this receptor for the appropriate functioning of neural stem cells, oligodendrocytes, and neurons. The constitutive knock-out (KO) of the receptor is embryonically lethal. To unravel the receptors' role in the developing brain we generated a mouse mutant by specifically targeting radial glia stem cells of the dorsal telencephalon. The low-density lipoprotein receptor-related protein-1 lineage-restricted KO female and male mice, in contrast to available models, developed a severe neurological phenotype with generalized seizures duri…
Selective α-synuclein knockdown in monoamine neurons by intranasal oligonucleotide delivery: potential therapy for parkinson’s disease
2018
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson’s disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration. Here, we used this strategy to conjugate inhibitory oligonucleotides, siRNA and antisense oligonucleotide (ASO), with the triple monoamine reuptake …
Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the a…
2015
Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of his…
Cellular composition and cytoarchitecture of the adult human subventricular zone: A niche of neural stem cells
2005
The lateral wall of the lateral ventricle in the human brain contains neural stem cells throughout adult life. We conducted a cytoarchitectural and ultrastructural study in complete postmortem brains (n = 7) and in postmortem (n = 42) and intraoperative tissue (n = 43) samples of the lateral walls of the human lateral ventricles. With varying thickness and cell densities, four layers were observed throughout the lateral ventricular wall: a monolayer of ependymal cells (Layer I), a hypocellular gap (Layer II), a ribbon of cells (Layer III) composed of astrocytes, and a transitional zone (Layer IV) into the brain parenchyma. Unlike rodents and nonhuman primates, adult human glial fibrillary a…
Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT
1996
By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminer…
Cell fate specification in an in vitro model of neural development
1998
We have studied in an in vitro model of neural development the effect of neighboring cells on the fate of single fluorescently labeled precursor cells. In one line of experiments, PCC7-Mz1 embryonal carcinoma cells were transiently transfected with "green fluorescent protein" (GFP) and, following incubation with 0.1 microM all-trans retinoic acid (RA), the number and morphology of derivatives (neuronal or non-neuronal) was determined that form groups of GFP-expressing cells in a surrounding of unlabeled cells. Because single PCC7-Mz1 cells can produce single-lineage and mixed-lineage derivatives, they are individually pluripotent. In another line of experiments, we have analyzed the fate of…
The effect of long context exposure on cued conditioning and c-fos expression in the rat forebrain
2004
The c-fos expression was used to study the neural substrates of the cued fear conditioning acquisition, preceded by a short exposure versus a long exposure to the conditioning context. A long-context exposure (either during the night or during the day) prior to conditioning, was associated with low freezing in the learning test. Differences in the c-fos expression of CA1, CA3, BL Amygdala, LS and BNST were found between the short- or long-context groups with a pre-exposure before cued conditioning. Ce Amygdala showed no differences in the c-fos expression labeling. We reported the hippocampal c-fos activation during the cued fear conditioning acquisition. Specifically, the CA1 activation co…
Distribution patterns of vimentin-immunoreactive structures in the human prosencephalon during the second half of gestation.
1999
Neuronal migration is guided by long radially oriented glial fibres. During late stages of development radial glial cells are transformed into astrocytes. A predominant intermediate filament protein within radial glial cells and immature astrocytes is vimentin. In this study fetal brain sections were used to demonstrate the transient features of vimentin-positive radial glia. In the lower half of the cerebral wall of the 6th gestational month bundles, curvature, and crossing of vimentin-positive fibres are regularly seen. Moreover, fibres terminating on vessels are observed. In the upper half fibres are radially oriented; when ascending towards the pial surface the number and diameter of fi…
Lack of APP and APLP2 in GABAergic Forebrain Neurons Impairs Synaptic Plasticity and Cognition.
2020
AbstractAmyloid-β precursor protein (APP) is central to the pathogenesis of Alzheimer’s disease, yet its physiological functions remain incompletely understood. Previous studies had indicated important synaptic functions of APP and the closely related homologue APLP2 in excitatory forebrain neurons for spine density, synaptic plasticity, and behavior. Here, we show that APP is also widely expressed in several interneuron subtypes, both in hippocampus and cortex. To address the functional role of APP in inhibitory neurons, we generated mice with a conditional APP/APLP2 double knockout (cDKO) in GABAergic forebrain neurons using DlxCre mice. These DlxCre cDKO mice exhibit cognitive deficits i…
Protective effects of mirtazapine in mice lacking the Mbnl2 gene in forebrain glutamatergic neurons: Relevance for myotonic dystrophy 1
2019
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and wasting and by important central nervous system-related symptoms including impairments in executive functions, spatial abilities and increased anxiety and depression. The Mbnl2 gene has been implicated in several phenotypes consistent with DM1 neuropathology. In this study, we developed a tissue-specific knockout mouse model lacking the Mbnl2 gene in forebrain glutamatergic neurons to examine its specific contribution to the neurobiological perturbations related to DM1. We found that these mice exhibit long-term cognitive deficits and a depressive-like state associated with neuronal loss, increa…