Neuroprotective Effects of Caffeine in Sleep Deprivation - Caffeine: Chemistry, Analysis, Function and Effects - page 299

The activity of the neural networks within the hippocampus can undergo
alterations in the strength of synaptic transmission as an outcome of repetitive
activity (Burgess et al 2002). These changes, known as synaptic plasticity,
represented by LTP, are believed to be correlates of learning and memory. Two
major phases of LTP have been established, the early-phase (E-LTP), which
utilizes calcium-calmodulin-dependent protein kinase II (CaMKII) phosphor-
ylation, and the late-phase (L-LTP), which requires protein synthesis through
activation of transcription factors such as CREB. The two phases are widely
considered as hypothetical models for short-term and long-term memory,
respectively (Malenka and Bear 2004).
Electrophysiological experiments in the CA1 and DG of anesthetized rats
indicate that chronic caffeine treatment does not alter normal basal synaptic
transmission (Alhaider et al 2010a; 2011). Additionally, chronic administration
of caffeine in normal rats has no effect on either E-LTP or L-LTP in both CA1
and DG regions of the hippocampus (Alhaider et al 2010a; 2011; Figure 16.2).
However, a positive effect of caffeine on plastic changes in synaptic
transmission has been reported. It has been shown that caffeine induces an
LTP-like response in the CA1 pyramidal neuron synapses in rat hippocampal
slices (Martin and Buno 2003). Consistent with this observation, caffeine can
mediate structural changes in cultured-hippocampal neurons by enhancing the
size of dendritic spines (Korkotian and Segal 1999). It is believed that caffeine
enhances the excitability of rat hippocampal neurons by antagonizing the
effects of adenosine on A 1 receptors. Adenosine produces an inhibitory effect
on LTP in area CA1 in rat hippocampal slices (de Mendonca and Ribeiro
1994).

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16.6 Caffeine and Neuroprotection
Although a low dose of chronic caffeine treatment in rats had no significant
effect on normal memory, it prevented memory loss of recent information
associated with acute SD (Alhaider et al 2010b; 2011, Figure 16.1). Thus, it
seems that at low chronic dose, caffeine worked as a protector rather than a
promoter of memory function. Interestingly, previous reports have demon-
strated the neuroprotective effects of chronic intake of caffeine in animal
models of ischemia (Sutherland et al 1991) as well as in human subjects (Maia
and de Mendonca 2002). Furthermore, the positive impact of caffeine on
learning and memory is supported by epidemiological studies, which
demonstrate an inverse correlation between coffee intake and the incidence
of Parkinson's disease and Alzheimer's disease later in life (Ascherio et al 2001;
Maia and de Mendonca 2002; Ritchie et al 2007). Consistent with this view, a
large body of evidence has shown that caffeine administration may be a
protective factor against memory impairment resulting from several animal
models of brain disorders including Alzheimer's disease (Dall'Igna et al 2007;
Arendash et al 2009; Cao et al 2009), Parkinson's disease (Gevaerd et al 2001),
attention deficit hyperactivity disorder (Prediger et al 2005), age-related