Title:A Derived Mechanism of Nervous System Functions Explains Aging-Related Neurodegeneration as a Gradual Loss of an Evolutionary Adaptation
VOLUME: 13 ISSUE: 2
Author(s):Kunjumon I. Vadakkan*
Affiliation:Neurosearch Center, 76 Henry Street, Toronto M5T1X2, ON
Keywords:Inter-cellular fusion, inter-cellular hemifusion, exocytosis, internal sensation, inter-spine fusion, spine loss, apoptosis.
Abstract:Background: Solving the nervous system requires understanding how it generates inner
sensations of "mind" within it. It was possible to derive a hypothesis of brain functions where the
formation of a spectrum inter-postsynaptic (inter-spine) functional LINKs (IPLs) are the key structural
changes responsible for encoding at the time of learning and are used for inducing the inner
sensation of memory, both taking place at millisecond timescales. Since stages of ontogeny reflect
possible stages of evolution, it is possible to examine whether IPLs have features of an evolved
mechanism.
Objective: To examine whether 1) IPLs have features of an evolved mechanism, 2) significant neuronal
death during ontogeny leads to evolutionary adaptations for preventing cell death among the
surviving neurons, and 3) loss of these adaptations lead to cellular changes that can cause agingrelated
neurodegeneration.
Methods: Key milestone changes of the ontogeny of the nervous system were examined to test
whether they match with a feasible sequence of steps that lead to the formation of IPLs.
Results: Several developmental stages can explain a probable sequence of events that lead to IPL
formation among synaptically-connected neurons. When internal sensations generated by the IPLs
started providing survival advantage, evolution has started preserving the IPL circuitry. A stage of
inter-spine fusion possibly leads to a) significant neuronal death during the early stages of development,
and b) trigger an adaptation in the surviving cells to stabilize and prevent the IPLs from
undergoing fusion. Since there are no irreversible steps for maintaining the stability of IPLs, agingrelated
factors may destroy the adaptation mechanism and destabilize the IPLs predisposing them
to cause neurodegeneration.
Conclusion: The derived testable IPL mechanism that can explain nervous system functions is capable
to have evolved. An adaptation to prevent IPL hemifusion from progressing to fusion is
likely the last stage of nervous system evolution. Since the IPL mechanism is utilized during every
event of learning, any aging-related factors that can weaken this adaptation can cause IPL fusion
and lead to neurodegeneration.
