Behavioral and molecular characterization of a triple transgenic mouse model of Alzheimer’s disease

FELD M; BOCCIA MM; BLAKE MG; KRAWCZYK MC; CASAL MJ; BARATTI CM; ROMANO A

Córdoba, Argentina

Congreso; IRCN First Joint Meeting of the Argentine Society for Neuroscience (SAN) and the Argentine Workshop in Neurosciences (TAN); 2009

Sociedad Argentina de Neurociencias

Progressive memory loss and cognitive dysfunction are the hallmark clinical features of AD. Moreover, senile plaques containing mainly amyloid-beta (Ab) peptides,neurofibrillary tangles composed of hyperphosphorylated tau (t), and neuronal loss are the major histological findings of AD. However, Ab are elevated without plaqueformation or nerve cell loss, yet learning and memory deficits are evident in early stages of AD. Identifying the molecular triggers for the onset of AD-related cognitivedecline presently requires the use of suitable animal models, such as the triple transgenic mouse model of AD (3xTg-AD), which develops both amyloid and tanglepathology (Oddo et al., 2003). Recently, it was proposed that memory deficits are caused by different states of Ab aggregation, particularly by soluble oligomers (Walshet al., 2002). But beyond its pathological role, Ab has also been proposed as a physiological synaptic transmission depressor in response to neuronal activity, as partof a negative-feedback mechanism (Kamenetz et al., 2003). Previous work in our lab has suggested a fine regulation of specific memory molecular pathways by Abaggregates administration in the crab Chasmagnathus (Feld et al., 2008), particularly the ERK/MAPK pathway. Although memory impairment was found after Abadministration in different paradigms (Flood et al., 1991; Delobette et al., 1997; Sun & Alkon, 2002; Jhoo et al., 2004; Sun and Alkon, 2004; Mileusnic et al., 2004;Prediger et al., 2007), it is currently unknown the nature of the memory deficits induced.The role of MAPK (mitogen-activated protein kinase) as well as that of the transcription factor NF-kB have been assessed in different models of synaptic plasticity andmemory in vertebrates as well as in invertebrates. Here we characterized the onset of learning and memory deficits in these transgenic mice, in addition to determiningdifferent molecular markers that correlate.