Long term osmotic stress exposure outcomes on rat dopaminergic innervations and the associated motor behavior.

The osmotic stress is a powerful stimulus that elicits profound peripheral and central disturbances. In the mammalian brain, osmotic stress has been associated to several glial and neuronal changes. The lack of data regarding the impact on the dopaminergic system and locomotion led us to investigate the effect of prolonged water deprivation in rat on the midbrain dopaminergic system and locomotor performance by dehydrating rats for one and two weeks.

Correct Laminar Positioning in the Neocortex Influences Proper Dendritic and Synaptic Development.

The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear.

Depolarizing γ-aminobutyric acid contributes to glutamatergic network rewiring in epilepsy.

Objective: Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy. Besides the rewiring of excitatory circuits, an abnormal depolarizing γ-aminobutyric acidergic (GABAergic) drive has been hypothesized to participate in the epileptogenic processes. However, a remaining clinically relevant question is whether early post-status epilepticus (SE) evoked chloride dysregulation is important for the remodeling of aberrant glutamatergic neuronal circuits.

Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20-30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epilepticus (SE) epilepsy.

MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation.

Proper morphogenesis of neuronal dendritic spines is essential for the formation of functional synaptic networks. However, it is not known how spines are initiated. Here, we identify the inverse-BAR (I-BAR) protein MIM/MTSS1 as a nucleator of dendritic spines.

Cortical GABAergic excitation contributes to epileptic activities around human glioma.

Brain gliomas are highly epileptogenic. Excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glioma cells.

Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.

We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes.

Enhanced Synaptic Activity and Epileptiform Events in the Embryonic KCC2 Deficient Hippocampus.

The neuronal potassium-chloride co-transporter 2 [indicated thereafter as KCC2 (for protein) and Kcc2 (for gene)] is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2(+/+)) and Kcc2 deficient (Kcc2(-/-)) mouse embryos, we unexpectedly found increased spontaneous neuronal network activity at E18.5, a developmental stage when KCC2 is thought not to be functional in the hippocampus.

Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital.

Phenobarbital produces its anti-epileptic actions by increasing the inhibitory drive of γ-aminobutyric acid. However, following recurrent seizures, γ-aminobutyric acid excites neurons because of a persistent increase of chloride raising the important issue of whether phenobarbital could aggravate persistent seizures. Here we compared the actions of phenobarbital on initial and established ictal-like events in an in vitro model of mirror focus.

Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling.

Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering.

Neuronal distribution of spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17.

We identified the Spatial (Stromal Protein Associated with Thymii and Lymph-node) gene from an adult thymus mouse library of cDNA clones. By RT-PCR, we reported that Spatial was highly expressed in restricted areas of the central nervous system. Here, we characterize the precise cellular localization of Spatial during mouse brain development in the cerebellum, hippocampus and cortex.

Mouse CD24 is required for homeostatic cell renewal.

Under physiological conditions, some adult tissues retain a capacity for self-renewal. This property is attributable to the proliferation and differentiation of stem, transit-amplifying, and differentiating cells, which are regulated by cell-cell or cell-matrix interactions or by secreted factors. By gain and loss of function experiments, we demonstrate the involvement of mouse CD24 (mouse cluster of differentiation 24), which is a glycosyl phosphatidylinositol (GPI)-anchored cell-surface glycoprotein, in the regulation of homeostatic cell renewal.

ABCA2 is a marker of neural progenitors and neuronal subsets in the adult rodent brain.

The notion that the ATP-binding cassette transporter-A2 (ABCA2) may be involved in brain sterol homeostasis and is associated with early onset Alzheimer's disease led us to explore its neural expression. Our data support and extend the previous reports on ABCA2 expression by oligodendrocytes. They evidence that ABCA2 (i) is located in intracellular vesicles, identified in transfected cells as lysosome-related organelles only partially overlapping with classical endolysosomes; (ii) is a marker of neural progenitors as it is expressed in the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampal formation, sites of continual neurogenesis in the adult brain, and in nestin(+) cells differentiated in vitro from embryonic stem cells; (iii) persists, in the adult rodent brain, in a subset of GABAergic and glutamatergic neurons.

mCD24 regulates proliferation of neuronal committed precursors in the subventricular zone.

We previously showed that deletion of the cell surface molecule mCD24 resulted in an increased proliferation in adult subventricular zone (SVZ). Here, we report an increased PSA-NCAM+/TuJ1- population in the mCD24-/- in vivo SVZ as well as in vitro neurospheres. Isolated in vitro, these cells were able to generate neurospheres.

Increased neurogenesis in adult mCD24-deficient mice.

mCD24, a glycosylphosphatidylinositol-anchored highly glycosylated molecule, is expressed on differentiating neurons during development. In the adult CNS, its expression is restricted to immature neurons located in two regions showing ongoing neurogenesis: the subventricular zone (SVZ) of the lateral ventricle pathway and the dentate gyrus (DG) of the hippocampal formation. Here, combining bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen labelings we confirmed that mCD24 is expressed on proliferating cells.