## 4 The Effect of RF Exposure _in Vivo_: New Insights on Biosystem Functions
### Physiopathology of the Brain  
The involvement of RF in several neuropathologies has received wide consideration [58]. Among the neurodegenerative diseases, Alzheimer's disease (AD) has long been associated with RF exposure. AD is in fact characterized by the presence of well-established morphological (neurofibrillary tangles and \(\beta\) amyloid deposition in cortical and hippocampal neurons) and functional (behavioral and memory alterations) biomarkers. One of the most relevant features of Alzheimer's seems to be the increased reactive oxygen species (ROS) production and related inflammation of cortical and subcortical tissue in AD brains. There are many reports of ROS increase after RF exposure in the brain [59,60] that in turn give rise to a cascade of molecular events involving anti-oxidative enzyme activities, protein kinase C, creatine kinase and finally the pro-apoptotic enzyme caspase 3. RF-dependent expression of reactive astroglia was also detected [56]. There seems to be a causal relation between AD development and RF exposure; however, few reports suggested a beneficial influence of RF on this pathology. Although recent evidence would suggest otherwise, [61,62] it has been demonstrated that chronic pulse application of RF can revert both deposition of \(\beta\) amyloid and ameliorate cognitive deficit in mice [63]. A similar effect was also obtained in either wild type and mutated mice [64], where RF exposure increased mitochondrial activity and reduced cerebral blood fluid and seemed to facilitate soluble \(\beta\) amyloid removal from the CNS district. Interestingly, [PERSON] and co-workers [65] pointed their attention to another aspect not yet fully investigated namely Wi-Fi radiofrequencies (2.40 GHz SAR 1.6 W/kg). 3\(\times\) Tg-AD transgenic mice [66] were exposed for 28 consecutive days and tested for cognitive and behavioral tasks. It appears that Wi-Fi exposure might determine a positive cognitive interference and a beneficial influence on anxiety. The authors are set to explore the molecular pathways that underlie these findings. Few reports concern [PERSON]'s disease (PD) and RF exposure. [PERSON]'s is another severe neurodegenerative disease and is caused by a degeneration of dopaminergic neurons in the _Substantia Nigra_ of the midbrain. A possible causal link between RF and PD has been suggested [67, 68]. Dopamine expression and the expression of those enzymes that participated in its metabolism, such as monoaninoxidases (MAOs), have also been investigated after RF exposure in rats [69]. Moreover, abnormal aggregation of \(\alpha\)-synuclein plays a crucial role in [PERSON]'s disease pathogenesis and its toxicity. The physiological function of \(\alpha\)-synuclein remains uncertain; however, \(\alpha\)-synuclein protein deposition in Lewy bodies is considered as a biomarker of PD because its accumulation, even to a small extent, may be a risk factor for neurodegeneration. In cultured neuron-enriched mixed cortical cell cultures from the brains of rat embryos, the expression of \(\alpha\)-synuclein was found to be down-regulated by 900 MHz acute exposure [70]. Long-term whole body irradiation of Balb/c mice showed altered protein expression in cerebellum, hippocampus, and frontal lobe. Most relevantly, \(\alpha\)-synuclein expression, together with glial fibrillary acidic protein (GFAP), glia maturation factor beta (GMF) and apolipoprotein E (apoE) expression, was altered, indicating impaired neuronal plasticity. Moreover, heat shock proteins, and cytoskeletal proteins also varied significantly, suggesting possible structural and morphological alterations in the RF exposed brain [71]. The real effect of RF exposure on PD induction and development remains uncertain. In relation to the CNS, it is worth mentioning a few studies on the effect of RF on neuronal blood barrier permeability. Blood-brain barrier (BBB) and blood-retinal barrier [72] are safety mechanisms that regulate molecular exchanges between blood circulation and neuronal tissues.