Cellular neuroscienceDifferential activation of mitogen-activated protein kinase signalling pathways in the hippocampus of CRND8 transgenic mouse, a model of Alzheimer's disease
Section snippets
Animals
Tg heterozygous TgCRND8 mice with a (C57)/(C57/C3H) genetic background and non-Tg littermates hybrid (C57)/(C57/C3H) wild type (Wt) control mice of 7 months of age were used. The mice were obtained from the laboratory of Prof. P. St. George-Hyslop (CRND, Toronto, ON, Canada) and were bred in the Centre for Laboratory Animals, University of Florence, Italy. The mice were housed in macrolon cages with ad libitum food and water and maintained on a 12-h light/dark cycle at 23 °C room temperature
Results
As reported in previous papers (Bellucci et al 2006, Bellucci et al 2007), TgCRND8 mice at 7 months of age show the presence of numerous β-amyloid deposit in the hippocampus and other brain areas, as well as astrocytes and microglia activation, inflammatory markers, nitrosative stress, neuronal damage, hyperphosphorylated tau, cholinergic dysfunction and impairment in learning and memory functions. Therefore, our work was aimed at understanding the intracellular pathways that might be switched
Discussion
Three main mammalian MAPK subfamilies have been described: ERK1,2, JNK, and p38MAPK kinase (Pearson et al., 2001). MAPKs are implicated in various cellular processes (Raman et al., 2007), and dysfunction of specific MAPKs is associated with diseases such as cancer and immunological disorders. In the nervous system, as well as in other tissues, activation of JNK and p38MAPK has often been correlated with death in various cell types, including neurons (Xia et al 1995, Kummer et al 1997,
Acknowledgments
This research was partly funded by PRIN 2005 and partly by Università di Firenze (ex 60%).
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2017, Neurobiology of Learning and MemoryThe integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal inhibitory avoidance memory
2015, Neurobiology of Learning and MemoryCitation Excerpt :ACh, released in the proximity of depolarized neurons, brings about a long-lasting potentiation of the postsynaptic membrane (Metherate, 1998; Tremblay, Warren, & Dykes, 1990). Stimulation of muscarinic/nicotinic receptors subtypes present on neurons (Berkeley et al., 2001; Dineley et al., 2001; Giovannini et al., 2008; Rosenblum, Futter, Jones, Hulme, & Bliss, 2000) may create conditions favourable for neuronal plasticity, initiating a network of signals that activate several intracellular transduction pathways including the ERK pathway (Gutkind, 1998). ERK is also activated by glutamate through metabotropic (Peavy & Conn, 1998) or ionotropic glutamate receptors (Krapivinsky et al., 2003; Zhu, Qin, Zhao, Van Aelst, & Malinow, 2002), by noradrenaline through β-adrenergic receptors (Watabe, Zaki, & O’Dell, 2000; Williams, Zhong, & Minneman, 1998; Winder et al., 1999), by other neurotransmitters (Drutel et al., 2001; Giovannini et al., 2003), and growth factors (Castillo & Escobar, 2011) and by the sex steroid hormones 17beta-estradiol and progesterone (Harburger, Saadi, & Frick, 2009; Orr, Rubin, Fan, Kent, & Frick, 2012).
B<inf>2</inf> receptor blockage prevents Aβ-induced cognitive impairment by neuroinflammation inhibition
2015, Behavioural Brain ResearchCitation Excerpt :This study provides the first evidence for a critical role of this receptor in the neuroinflammatory processes related to AD. Aβ-induced neuroinflammation might be orchestrated by the activation of different MAPKs and their downstream transcription factors [34,19]. We have previously shown that Aβ1–40 i.c.v. injection stimulates the activation (phosphorylation) of JNK and its transcription factor c-Jun, as well as p38 and the transcription factor NF-κB [16].
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2015, Neurobiology of AgingThe role of ERK1/2 in the regulation of proliferation and differentiation of astrocytes in developing brain
2013, International Journal of Developmental NeuroscienceCitation Excerpt :ERK1/2 may also play an important role in the deterioration process of neurodegeneration diseases. In this context, the ERK2 isoform was less activated in the hippocampal dentate gyrus of Tg mice that express a double mutant form of the human amyloid precursor protein and thus represents a good model of Alzheimer's disease in basal conditions and after cholinergic stimulation (Giovannini et al., 2008). These findings may provide constructive ideas about possible mechanisms that lead to memory and cognitive ability loss in the pathogenesis of neurodegeneration.
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Present address: Division of Pharmacology, Department of Biomed. and Biotechnol. Sci., University of Brescia, Viale Europa 11, 25123 Brescia, Italy (A. Bellucci).