A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the in barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics’ avoidance of the closed arms in the plus maze.

Exposure to environmental enrichment has been shown to induce robust neuronal plasticity in both intact and injured adult central nervous system, including up-regulation of multiple neurotrophic factors, enhanced neurogenesis in the dentate gyrus of the hippocampus, and improved spatial learning and memory function. Neuronal plasticity, though mostly adaptive and abnormal, also occurs during certain neurodegenerative conditions such as the temporal lobe epilepsy (TLE). The TLE is characterized by hippocampal neurodegeneration, aberrant mossy fiber sprouting, spontaneous recurrent motor seizures, cognitive deficits, and abnormally enhanced neurogenesis during the early phase and dramatically declined neurogenesis during the chronic phase of the disease. As enrichment has been found to be beneficial for treating animal models of Alzheimer's, Parkinson's, and Huntington's diseases, there is considerable interest in determining the efficacy of this strategy for preventing or treating chronic TLE after the initial precipitating brain injury. This review first discusses the proof of principle behind the potential application of the environmental enrichment strategy for preventing or treating TLE after brain injury. The subsequent chapters confer the portrayed beneficial effects of enrichment for functional post-lesional recovery in TLE and the possible complications which may arise from housing epilepsy-prone or epileptic rats in enriched environmental conditions. The final segment discusses studies that are essential for further understanding the efficacy of this approach for preventing or treating TLE.

Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior.

Thus, the current study highlights the possibilities of treating neurodegenerative diseases with "Nano" size exosomes as opposed to transplanting billions of stem cells which inherit several disadvantages.