Activation of cAMP Signaling Facilitates the Morphological Maturation of Newborn Neurons in Adult Hippocampus

Abstract

Previous studies have demonstrated that activation of the cAMP cascade, including the cAMP response element-binding protein (CREB), increases the proliferation and survival of newborn neurons in adult mouse hippocampus. In the present study, we determined whether the cAMP-CREB cascade also influences the morphological maturation of newborn neurons in the subgranular zone of the hippocampus. Rolipram, a selective inhibitor of the cAMP-specific phosphodiesterase type 4, was administered to activate the cAMP cascade, and neuronal morphology was determined by analysis of Golgi-impregnated neurons in the subgranular zone of hippocampus. Rolipram administration significantly increased the number of branch points and length of dendrites relative to vehicle treatment. Increased branch number and length were accompanied by increased levels of phosphorylated CREB, the active form of this transcription factor, in immature neurons. In contrast, the morphology of Golgi-impregnated neurons was not significantly influenced by rolipram treatment in inducible transgenic mice expressing a dominant-negative mutant of CREB in hippocampus. We also tested the influence of cAMP analogs in primary hippocampal cultures and found that activation of the cAMP pathway increased and inhibition of the cAMP cascade decreased the number of branches and length of processes as observed in vivo. These findings indicate that the cAMP-CREB cascade plays an important role in the differentiation and maturation of newborn neurons in hippocampus.

A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition

“…This pattern could be related to the intrinsic properties of neurons or a cell type-specific contribution of Disc1 during embryonic and postnatal development dictated, at least in part, by its expression pattern (15). The mechanism behind the cellular aberrations may be related to the putative role of Disc1 at the centrosome (7) or in controlling cAMP levels (5,(27)(28)(29), although we cannot exclude other, yet-unexplored pathways. Morphological disturbances consistent with dendritic misorientation or impaired dendritic growth have been described in schizophrenia, albeit inconsistently (30,31), and a recent study provided preliminary evidence for impaired adult neurogenesis in individuals with schizophrenia (32).…”

Male behavioural maturation rate responds to selection on pollen hoarding in honeybees

“…These cascades are important in a variety of contexts (Antoni 2000;Jordan et al 2000) and the underlying genes are good candidates for wide-ranging pleiotropic effects. cAMP signalling has been specifically implicated in maturation of the nervous system (Fujioka et al 2004) and thus may be responsible for at least one of the observed differences between drones of the high-and low-pollen-hoarding strains.…”

Cyclic AMP-mediated Regulation of Transcription Factor Lot1 Expression in Cerebellar Granule Cells

“…Approximately 5 g of RNA were digested with 10 units of RNase-free DNase (Promega) for 30 min at 37°C. After DNase inactivation, RNA was retrotranscribed with an oligo(dT) [12][13][14][15][16][17][18] primer (0.5 M) and 200 units of Moloney murine leukemia virus reverse transcriptase (Invitrogen) according to the manufacturer's instructions. For real-time PCR, the following Lot1, glyceraldehyde-3-phosphate dehydrogenase, and c-fos primers were used: rat Lot, 5Ј-TTAGCTGCGTAGTTGCGTGTTA-3Ј (sense) and 5Ј-CGGGTCCCTGAAAAGAACACA-3Ј (antisense); glyceraldehyde-3-phosphate dehydrogenase, 5Ј-GAACATCATCCCTGCATCCA-3Ј (sense) and 5Ј-CCAGTGAGCTTCCCGTTCA-3Ј (antisense); and c-fos, 5Ј-TGGACCTGTCTGGTTCCTTC-3Ј (sense) and 5Ј-ATG-CACCAGCTCAGTCAGTG-3Ј (antisense).…”

“…Recent studies have reported that the cAMP-PKA cascade is one of the key signal transduction pathways involved in neuronal proliferation (13,14). To define the effects of adenylate cyclase activation on CGC proliferation, we analyzed BrdUrd incorporation in cells exposed to PACAP or forskolin for 24 h after cell plating.…”

“…Therefore, identifying factors that are involved in the regulation of Lot1 expression during CGC differentiation could represent an important step toward deciphering a possible relationship between Lot1 expression and neurogenesis. Evidence from both in vivo and inculture studies suggests that several steps of neurogenetic process are crucially linked to an increase in intracellular cAMP (13,14). cAMP is a second messenger that regulates a striking number of physiological processes, including intermediary metabolism, cell proliferation, and neuronal signaling, by altering the basic pattern of gene expression (15)(16)(17).…”