Impact of the BDNF Val66Met polymorphism within and beyond the retrosplenial cortex in females with Mild Cognitive Impairment: A magnetoencephalography study

Mild Cognitive Impairment (MCI) can be influenced by genetic risk factors. The Brain Derived Neurotrophic Factor Val66Met polymorphism is one of them. This mutation may affect the brain functional connectivity (FC), especially for those carriers of the Met allele (A). The retrosplenial cortex (RSC), essential component of the Default Mode Network (DMN), could be altered by this polymorphism. Our aim was to examine the influence of the Val66Met polymorphism within the RSC?s functional network, and its interconnections between the frontal medial cortex (FMC) and the anterior cingulate (ACC)

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection

Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site. Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid receptors, the molecular target for marijuana-derived compounds. Indeed, activation of cannabinoid receptors reduces the production and diffusion of harmful mediators. Here, we provide evidence that an exception to this pattern is found in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that cell damage induced by EAE does not lead to increase in eCBs, even though cannabinoid receptors are functional because synthetic cannabinoid agonists are known to confine EAE-induced lesions. This lack of eCB increase is likely due to IFN-γ, which is released by primed T cells invading the CNS. We show that IFN-γ disrupts the functionality of purinergic P2X(7) receptors, a key step controlling eCB production by microglia, the main source of eCBs in brain. Accordingly, induction of EAE in P2X(7)(−/−) mice results in even lower eCB levels and more pronounced cell damage than in wild-type mice. Our data suggest that the high level of CNS IFN-γ associated with EAE disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat multiple sclerosis

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment

The original publication can be found at www.springerlink.comObjective Aim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI. Methods 17 healthy subjects (age = 69 ± 3, 9 females), and 23 amnestic MCI patients (age = 70 ± 6, 10 females) underwent brain MR scan and 99mTc ECD SPECT. Conversion to AD was ascertained on average 19 ± 10 months after baseline: 9 had converted (age = 69 ± 3, 4 females), and 14 had not (age = 71 ± 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol.We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis. Results In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side.We found no overlap between significant atrophy and significant hypoperfusion regions. Conclusions Parahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.A. Caroli, C. Testa, C. Geroldi, F. Nobili, L. R. Barnden, U. P. Guerra, M. Bonetti and G. B. Frison