Early impairment of synaptic plasticity in patients with Down’s syndrome
Fortunato Battaglia a,∗ , Angelo Quartarone b , Vincenzo Rizzo b , Maria Felice Ghilardi a , Alessandro Di Rocco d , Gaetano Tortorella c , Paolo Girlanda b
CUNY School of Medicine, Department of Physiology and Pharmacology, 138th Street & ConventAvenue, Room D-210, New York, NY 10031, United States b Institute of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, Italy c Department of Child Neuropsychiatry, University of Messina, Italy d Department of Neurology, New York University, New York, NY, United States Received 5 December 2006; received in revised form 13 February 2007; accepted 19 February 2007Available online 30 March 2007
Abstract We investigated synaptic plasticity in persons with Down’ syndrome (DS) and control subjects used paired associative stimulation (PAS) protocol, a paradigm capable of producing long-term potentiation (LTP)-like changes in the sensorimotor system. After PAS, patients showed less LTP-like plasticity compared to control subjects. Abnormal motor cortex synapticplasticity may play a role in the development of motor signs in DS. © 2007 Published by Elsevier Inc.
Keywords: Transcranial magnetic stimulation; LTP; Down’s syndrome
1. Introduction Down syndrome (DS) results from chromosomal aneuploidy (trisomy 21) and is the most common cause of mental retardation (Mann, 1988). Several studies demonstrated that patients with DS experience an age-dependentdecline in cognitive and motor performances. In at least 50% of patients after the age of 50 cognitive impairment progresses to a dementia syndrome resembling characteristics of Alzheimer’s disease (AD) (Evenhuis, 1990; Lai and Williams, 1989). By the fourth decade patients usually have important AD-like pathology (senile plaques and neuroﬁbrillary tangles) (Mann et al., 1984; Wisniewski et al.,1985; Hof et al., 1995). Cortical pathology is prominent in DS even in
Abbreviations: DS, Down’s syndrome; LTP, long-term potentiation; TMS, transcranial magnetic stimulation The authors do not have actual or potential conﬂicts of interest. The protocol was approved by the IRB of the University of Messina, Italy. ∗ Corresponding author. Tel.: +1 212 650 7964; fax: +1 212 650 7726. E-mail address:firstname.lastname@example.org (F. Battaglia). 0197-4580/$ – see front matter © 2007 Published by Elsevier Inc. doi:10.1016/j.neurobiolaging.2007.02.025
infancy (Becker et al., 1991). Typically, in younger individuals pyramidal neuron show reduced dendritic arborization and spine atrophy and A accumulation is manifested by diffuse deposits that are not associated with neuritic degeneration (Hof et al., 1995).Therefore, taking into account the developmental abnormalities, early DS can be considered a predementia model of AD. Long-term potentiation (LTP) is a form of synaptic plasticity considered to be a correlate of learning and memory. In a well-characterized DS mouse model, the Ts65Dn mouse, hippocampal LTP is reduced in the CA1 and the dentate gyrus (Siarey et al., 1997; Kleschevnikov et al.,2004). It is now possible to study LTP-like plasticity in humans with Paired Associative Stimulation (PAS) (Stefan et al., 2000). Electrical stimulation of the median nerve followed by a magnetic pulse on the primary motor cortex (M1) induces a long-lasting, LTP-like increase in the amplitude of motor evoked potential (MEP) registered in the target muscle with the interstimulus interval (ISI) at 25 ms(Stefan et al., 2000). These changes are long-lasting, (Stefan et al., 2000) depends upend the activity of the N-methyl-d-aspartate (NMDA) receptor (Stefan
F. Battaglia et al. / Neurobiology of Aging 29 (2008) 1272–1275
et al., 2002) and are temporarily occluded by prior motor training (Stefan et al., 2006; Ziemann et al., 2004). These characteristics points towards an LTP-like...