Pathological and non-pathological aging, SAMP8 and SAMR1. What do hippocampal neuronal populations tell us?

Abstract

ABSTRACTAlterations of cognitive processes and memory are one of the most important manifestations related to aging. However, not all memory types are affected in the same way. Learning and spatial memory are susceptible to these changes. The hippocampus represents the anatomical substrate of this type of memory, affected by structural and functional alterations along the normal aging and neurological diseases such as Alzheimer’s disease, Parkinson’s, schizophrenia and epilepsy. Some of the alterations related to aging are associated with alterations in the hippocampal interneuron populations and with an increase in excitability in the hippocampal circuit.In order to understand better the underlying processes in normal and pathological aging mechanisms, a murine model (Senescence-Accelerated Mouse Prone, SAMP8) and its respective controls (Senescence-Accelerated Mouse Resistant, SAMR1) have been used. While SAMP8 is a naturally occurring mouse line that displays a phenotype of accelerated aging with learning and memory impairment and these changes of learning and memory might be linked to some alterations in neuronal populations of the hippocampus. Thus, we analyzed the distribution and density of PV, CR and STT interneurons in the hippocampus of young and old mice as well as possible morphological and cholinergic changes in hippocampal formation. Comparing SAMR1 and SAMP8 we did not find any neural population that was specifically affected by aging in both groups. Interestingly, CR immunoreactivity and STT immunoreactivity showed changes in SAMP8 mice when they were compared to their controls. In SAMP8 CR+ and STT+ neurons decreased significantly along aging which suggests that CR and STT interneurons play a more important role than PV neurons in the pathological aging of the brain. In the case of SAMP8 mice the neural changes might be related to changes of the cholinergic system that might be affecting the wiring into the hippocampus formation through the perforant pathway. Further studies of this local circuitry will help to comprehend better how different inputs into these neural populations of the hippocampus could be affecting the development of neurodegerative diseases.