The Role of Galanin in Cerebellar Granule Cell Migration in the Early Postnatal Mouse during Normal Development and after Injury.

Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy).

The role of calcium and cyclic nucleotide signaling in cerebellar granule cell migration under normal and pathological conditions.

In the developing brain, immature neurons migrate from their sites of origin to their final destination, where they reside for the rest of their lives. This active movement of immature neurons is essential for the formation of normal neuronal cytoarchitecture and proper differentiation. Deficits in migration result in the abnormal development of the brain, leading to a variety of neurological disorders.

Cortical-layer-specific effects of PACAP and tPA on interneuron migration during post-natal development of the cerebellum.

During early post-natal development of the cerebellum, granule neurons (GN) execute a centripetal migration toward the internal granular layer, whereas basket and stellate cells (B/SC) migrate centrifugally to reach their final position in the molecular layer (ML). We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates in vitro the expression and release of the serine protease tissue-type plasminogen activator (tPA) from GN, but the coordinated role of PACAP and tPA during interneuron migration has not yet been investigated. Here, we show that endogenous PACAP is responsible for the transient arrest phase of GN at the level of the Purkinje cell layer (PCL) but has no effect on B/SC.

Spatio-temporal characterization of the pleiotrophinergic system in mouse cerebellum: evidence for its key role during ontogenesis.

The development of the central nervous system requires an appropriate micro-environment that is conditioned by a combination of various extracellular components. Most of the known signaling factors, such as neurotransmitters or neuropeptides, are soluble and diffuse into the extracellular matrix. However, other secreted molecules like proteoglycans or glycosaminoglycans anchor in the extracellular matrix to influence cerebral ontogenesis.

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development.

Light stimuli control neuronal migration by altering of insulin-like growth factor 1 (IGF-1) signaling.

The role of genetic inheritance in brain development has been well characterized, but little is known about the contributions of natural environmental stimuli, such as the effect of light-dark cycles, to brain development. In this study, we determined the role of light stimuli in neuronal cell migration to elucidate how environmental factors regulate brain development. We show that in early postnatal mouse cerebella, granule cell migration accelerates during light cycles and decelerates during dark cycles.

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and tissue plasminogen activator (tPA) play important roles in neuronal migration and survival. However, a direct link between the neurotrophic effects of PACAP and tPA has never been investigated. In this study, we show that, in PC12 cells, PACAP induced a 9.

Role of PACAP in controlling granule cell migration.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide, regulates a wide variety of cellular functions, but little is known about its role in neuronal cell migration. Recent studies revealed that PACAP has short-term, cortical layer-specific effects on neuronal cell migration. In this article, we focus on the role of PACAP in controlling the migration of cerebellar granule cells.

TRH acts as a multifunctional hypophysiotropic factor in vertebrates.

Thyrotropin-releasing hormone (TRH) is the first hypothalamic hypophysiotropic neuropeptide whose sequence has been chemically characterized. The primary structure of TRH (pGlu-His-Pro-NH(2)) has been fully conserved across the vertebrate phylum. TRH is generated from a large precursor protein that contains multiple repeats of the TRH progenitor tetrapeptide Gln-His-Pro-Gly.

Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum.

There is now strong evidence for non-immune or inflammatory functions of complement, notably in the central nervous system. In particular, it has been recently reported that the anaphylatoxin receptors C3aR and C5aR are transiently expressed in the cerebellar cortex of newborn rat, suggesting that anaphylatoxins are involved in the histogenesis of the cerebellum. In the present study, we have investigated the effects of C3aR and C5aR agonists and antagonists on the development of the cerebellum of 11-12-day-old rats in vivo and in vitro.

Biological and structural analysis of truncated analogs of PACAP27.

The affinity toward the PAC1 receptor, the biological activity, and the alpha-helical content of several truncated PACAP27 analogs were measured. We first evaluated the pharmacological and structural parameters of C-terminal shortened PACAP fragments, from PACAP(1-23) to PACAP(1-19). All carboxy-truncated derivatives demonstrated circular dichroism spectra typical of a helical conformation.

Neurotrophic effects of PACAP in the cerebellar cortex.

In the rodent cerebellum, PACAP is expressed by Purkinje neurons and PAC1 receptors are present on granule cells during both the development period and in adulthood. Treatment of granule neurons with PACAP inhibits proliferation, slows migration, promotes survival and induces differentiation. PACAP also protects cerebellar granule cells against the deleterious effects of neurotoxic agents.