Localization of synapsin I in normal fibers and regenerating axonal sprouts of the rat sciatic nerve

Abstract

The localization of synapsin I, a synaptic vesicle-associated protein, was investigated immunocyto-chemically in normal nerve fibers and regenerating axonal sprouts following crush-injuries to the rat sciatic nerve. In normal myelinated axons, weak synapsin I immunoreactivity was found in the axoplasmic/smooth endoplasmic domains, but not in the cytoskeletal domains comprising neurofilaments and microtubules. In non-myelinated axons without dense cytoskeletal structures, moderate immunoreactivity was distributed diffusely throughout the axoplasm. In the crush-injured nerves, intense synapsin I immunoreactivity was demonstrated by light microscopy in early regenerating sprouts emerging from nodes of Ranvier. These nodal sprouts subsequently elongated as regenerating axons through the space between the basal lamina and the myelin sheath (or Schwann cell plasma membrane). Intense synapsin I immunoreactivity was also found in the growth cones of such long regenerating axons. Electron microscopy revealed that synapsin I immunoreactivity was associated mainly with vesicular organelles in the nodal sprouts and growth cones of regenerating axons. Long regenerating axons exhibited no synapsin I immunoreactivity in the shaft, which contained an abundance of neurofilaments. However, vesicle accumulations remaining in the periphery of the shaft still exhibited intense synapsin I immunoreactivity. Thus, it can be concluded that synapsin I is localized at especially high density in the domains comprising vesicular organelles, which are characteristic of early nodal sprouts, as well as in growth cones of regenerating axons. These findings, together with the proposed functions of synapsin I investigated in other studies, suggest that synapsin I may play important roles in vesicular dynamics including the translocation of vesicles to the plasma membrane in sprouts and growth cones of regenerating axons.

Voluntary exercise increases axonal regeneration from sensory neurons

“…Increase in synapsin I and GAP43 mRNAs during exercise likely illustrates an overlap between retrograde signals induced by activity and injury. Synapsin I is a synaptic vesicle protein that is up-regulated after nerve injury in some systems, and this fact has been suggested to provide the growing axon with a source of axoplasmic membranes (34). The inhibitory effect of K252A pretreatment on the exercise-dependent increase in synapsin I mRNA indicates that activation of neurotrophin receptors during exercise positively regulates synapsin I expression.…”

Exercise induces BDNF and synapsin I to specific hippocampal subfields

“…Furthermore, both kindled seizures (Cavazos et al, 1991) and LTP (Adams et al, 1997) induce gross mossy fiber sprouting. Warranted by the ability of synapsin I to regulate neurite development (Melloni et al, 1994; Zurmohle et al, 1996), the formation and maintenance of the presynaptic structure (Sato et al, 2002), axonal elongation (Akagi et al, 1996) and new synaptic formation (Ferreira et al, 1998), it is presumed that increases in synapsin I lead to changes in synaptic circuitry (Greengard et al, 1993; Morimoto et al, 1998; Suemaru et al, 2000). Exercise‐induced increases in synapsin I in CA3 and DG thus may be indicative of mossy fiber sprouting.…”

“…The ability of BDNF to influence neural function may be intrinsic to its ability to modulate synaptic transmission by regulating synapsin I through its tyrosine kinase B (TrkB) receptor (Jovanovic et al, 2000). Synapsin I is a vesicle‐associated phosphoprotein that modulates transmitter release (Jovanovic et al, 2000), the formation and maintenance of the presynaptic structure (Takei et al, 1995), and axonal elongation (Akagi et al, 1996). The finding that BDNF is localized in close proximity to synapsin I (Haubensak et al, 1998) suggests that the hippocampal subfield localization of BDNF and synapsin I may be an important determinant as to which hippocampal regions are subject to regulation by BDNF during exercise.…”

Biological Mechanisms of Physical Activity in Preventing Cognitive Decline

“…Besides modulating transmitter release, synapsin I is involved in the formation and maintenance of the presynaptic structure (Melloni et al 1994) and in axonal elongation (Akagi et al 1996). An adequate vesicular release pool and adequate and sustainable transmitter release provided by functional levels of synapsin I may provide the level of synaptic communication necessary for learning.…”