Lysophosphatidic acid (LPA) is a simple phospholipid with extracellular signaling properties mediated by specific G protein-coupled receptors. At least 2 LPA receptors, LPAsub1 and LPAsub2, are ...expressed in the developing brain, the former enriched in the neurogenic ventricular zone (VZ), suggesting a normal role in neurogenesis. Despite numerous studies reporting the effects of exogenous LPA using in vitro neural models, the first LPAsub1 loss-of-function mutants reported did not show gross cerebral cortical defects in the 50% that survived perinatal demise. Here, we report a role for LPAsub1 in cortical neural precursors resulting from analysis of a variant of a previously characterized LPAsub1-null mutant that arose spontaneously during colony expansion. These LPAsub1-null mice, termed maLPAsub1, exhibit almost complete perinatal viability and show a reduced VZ, altered neuronal markers, and increased cortical cell death that results in a loss of cortical layer cellularity in adults. These data support LPAsub1 function in normal cortical development and suggest that the presence of genetic modifiers of LPAsub1 influences cerebral cortical development.
Lysophosphatidic acid (LPA) is a simple phospholipid with extracellular signaling properties mediated by specific G protein-coupled receptors. At least 2 LPA receptors, LPA sub(1) and LPA sub(2), are ...expressed in the developing brain, the former enriched in the neurogenic ventricular zone (VZ), suggesting a normal role in neurogenesis. Despite numerous studies reporting the effects of exogenous LPA using in vitro neural models, the first LPA sub(1) loss-of-function mutants reported did not show gross cerebral cortical defects in the 50% that survived perinatal demise. Here, we report a role for LPA sub(1) in cortical neural precursors resulting from analysis of a variant of a previously characterized LPA sub(1)-null mutant that arose spontaneously during colony expansion. These LPA sub(1)-null mice, termed maLPA sub(1), exhibit almost complete perinatal viability and show a reduced VZ, altered neuronal markers, and increased cortical cell death that results in a loss of cortical layer cellularity in adults. These data support LPA sub(1) function in normal cortical development and suggest that the presence of genetic modifiers of LPA sub(1) influences cerebral cortical development.
Neurogenesis persists in certain regions of the adult brain including the subgranular zone of the hippocampal dentate gyrus wherein its regulation is essential, particularly in relation to learning, ...stress and modulation of mood. Lysophosphatidic acid (LPA) is an extracellular signaling phospholipid with important neural regulatory properties mediated by specific G protein-coupled receptors, LPA
1–5. LPA
1 is highly expressed in the developing neurogenic ventricular zone wherein it is required for normal embryonic neurogenesis, and, by extension may play a role in adult neurogenesis as well. By means of the analyses of a variant of the original LPA
1-null mutant mouse, termed the Malaga variant or “maLPA
1-null,” which has recently been reported to have defective neurogenesis within the embryonic cerebral cortex, we report here a role for LPA
1 in adult hippocampal neurogenesis. Proliferation, differentiation and survival of newly formed neurons are defective in the absence of LPA
1 under normal conditions and following exposure to enriched environment and voluntary exercise. Furthermore, analysis of trophic factors in maLPA
1-null mice demonstrated alterations in brain-derived neurotrophic factor and insulin growth factor 1 levels after enrichment and exercise. Morphological analyses of doublecortin positive cells revealed the anomalous prevalence of bipolar cells in the subgranular zone, supporting the operation of LPA
1 signaling pathways in normal proliferation, maturation and differentiation of neuronal precursors.
The subcommissural organ (SCO) is an ependymal brain gland that secretes into the cerebrospinal fluid glycoproteins that polymerize, forming Reissner’s fiber (RF). The SCO–RF complex seems to be ...involved in vertebrate nervous system development, although its role in adults is unknown. Furthermore, its physiology is still greatly undetermined, and little is known about the release control of SCO secretion and the underlying intracellular mechanisms. In this report, we show that up to 90% of 3–5-day-old in vitro SCO cells from both intact and partially-dispersed SCO explants displayed spontaneous cytosolic Ca
2+ oscillations. The putative role of these spontaneous calcium oscillations in SCO secretory activity is discussed taking into consideration several previous findings. Two distinct subpopulations of SCO cells were detected, each one containing cells with synchronized calcium oscillations. A possible existence of different functional domains in SCO is therefore discussed. Oscillations persisted in the absence of extracellular Ca
2+, indicating the major involvement of Ca
2+ released from internal stores. Depolarization failed to induce intracellular calcium increases, although it disturbed the oscillation frequency, suggesting a putative modulator role of depolarizing agonists on the calcium oscillating pattern through voltage-gated calcium channels. Carbachol, a cholinergic agonist, evoked a switch in Ca
2+ signaling from a calcium oscillating mode to a sustained and increased intracellular Ca
2+ mode in 30% of measured cells, suggesting the involvement of acetylcholine in SCO activity, via a calcium-mediated response.
Galanin is a brain-gut peptide present in the central nervous system of fish, amphibians, birds, and mammals. For comparative studies among vertebrates, the distribution of galanin in the brain of ...reptiles has been investigated. We studied the localization of galanin-like-immunoreactive perikarya and nerve fibers in the brain of the turtle Mauremys caspica by using an antiserum against porcine galanin. In the telencephalon, few immunoreactive perikarya were seen in the amygdaloid complex. The diencephalon contained the majority of the immunoreactive perikarya present in the lamina terminalis, nucleus periventricularis anterior, lateral preoptic area, nuclei hypothalamicus ventromedialis and posterior, nucleus basalis of the anterior commissure, and nucleus ventralis tuberis. Many immunoreactive cells, especially in the infundibulum, contacted the cerebrospinal fluid by an apical process. In the rhombencephalon, immunopositive perikarya were restricted to a few cells in the nucleus tractus solitari. In the mesencephalon, they were absent. Immunoreactive nerve fibers were present in all regions containing labeled perikarya and in 1) telencephalon: septum, nucleus fasciculi diagonalis Brocae; 2) diencephalon: nucleus paraventricularis, nucleus supraopticus, nucleus suprachiasmaticus, subventricular grey, nucleus of the paraventricular organ, nucleus mamillaris, infundibular decussation, outer layer of the median eminence, posterior commissure and subcommissural organ region, habenula, nuclei dorsomedialis anterior, and dorsolateralis anterior of the thalamus; and 3) mesencephalon and rhombencephalon: stratum griseum periventriculare, stratum fibrosum periventriculare, laminar nucleus of the torus semicircularis, periventricular grey, nucleus interpeduncularis, nucleus ruber, substantia nigra, locus coeruleus, raphe nuclei, nuclei of the reticular formation, nucleus motorius nervi trigemini, cochlear and vestibular area, and nucleus spinalis nerve trigemini. Our results suggest that galanin may have hypophysiotropic and central roles in the turtle Mauremys caspica.
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