Hippocampus dysfunction

Moreover, all cells are not equally targeted in Alzheimer s disease, a disease that has discernable effects on consciousness (Perry et al., 1999). Large pyramidal cells of the frontal and temporal cortex, as well as the large pyramidal cells in CAl of hippocampus and subiculum, are the most susceptible to develop neurofibrillary tangles, to become dysfunctional and ultimately to die (Mann, 1996). It is the accumulation of abnormally hyperphosphorylated tau that disrupts the microtubular system of pyramidal cells in cortex and hippocampus both in experimental animal models and in Alzheimer s disease brain (Gong et al., 2000). 

One hypothesis is that an impairment ofserotonergic transmission through hippocampal 5-HTia receptors may underlie the low mood seen in depression. In addition, the reduced activation of hippocampal 5-HTia receptors may decrease the inhibitory control of the HPA axis mediated by the hippocampus leading to hypercortisolaemia and a neuropsychological impairment. An alternative hypothesis is that the primary neurobiological disturbance in depression is an abnormality of GRs leading to an impaired feedback control of the HPA axis and hypercortisolaemia. This in turn may lead to neuropsychological dysfunction. Reduced functional activity of GRs may increase the autoinhibitory action of somatodendritic 5-HTja receptors, decrease 5-HTia receptor num-... 

Of particular interest is that the A6 oligomers implicated in AD were shown to reduce PAKl and PAK3 expression levels and activities in the hippocampus and temporal cortex, resulting in a loss of drebrin from the spines and synaptic dysfunctions (Zhao et al., 2006 Ma et al., 2008). Drebrin is localized at spines in adult brains and is required for active clustering and synaptic targeting of PSD95... 

---