Alterations in heavy and light neurofilament proteins in hippocampus following chronic ECS administration

Abstract

Chronic administration of electroconvulsive seizures (ECS), one of the most effective treatments for depression, induces sprouting of the mossy fibers in the hippocampus. This sprouting requires chronic ECS administration and appears to occur in the absence of hilar neuronal loss. Dynamic regulation of cytoarchitecture plays a vital role in such profound alterations of neuronal morphology. In particular, alterations in the neurofilament protein subunits have been implicated in neurite sprouting, neuronal regeneration, and growth. The present study was carried out to determine the influence of chronic ECS administration on the neurofilament subunits and other molecular markers of neuronal plasticity. Chronic ECS administration decreases the level of phosphorylated heavy neurofilament subunit (NF-H). In addition, the total level of the light neurofilament subunit (NF-L) but not the medium neurofilament subunit (NF-M) is decreased following chronic ECS treatment. Other cytoskeletal proteins, including actin, microtubule-associated protein (MAP-2), and tau, are not influenced by chronic ECS administration. Expression of the growth-associated protein (F1/GAP-43) also remains unchanged following chronic ECS treatment. The changes observed in neurofilaments may be part of the cytoskeletal remodeling that contributes to the mossy fiber sprouting induced by chronic ECS treatment.

Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration

“…Nefl functions in cytoskeletal organization and cell-surface receptor remodeling [41,42], which may be impaired with the observed decrease in expression at 1-day of abstinence. Previously, changes in protein levels and post-translational modifications of Nefl, and other neurofilament isoforms, have been reported with cocaine, morphine, alcohol, and nicotine administration [43-45].…”

“…Persistent reductions in levels of CD47 and Arc, and inductions in levels of Drd5 and NPY suggest altered synaptic plasticity process involved in memory formation and removal of old memory traces, respectively [50,57,58]. A potential reduction in synaptic plasticity in the mPFC with cocaine self-administration/abstinence is hypothesized based on levels of CD47, Nefl, Arc, Egr1, and NPY [39,42,48-50]. These data are in agreement with studies of the direct role of psychostimulants on mechanisms of synaptic plasticity, including LTP and LTD, in the mesolimbic system [59,60].…”

Neuronal cytoskeletal alterations in an experimental model of depression

“…Since changes in the NFM and NFH morphological structure were not observed, increased soluble or altered assembly forms of these subunits are hardly tenable. It has been previously proposed that a decrement in NFL along with no changes in the other two subunits could be due to the highest vulnerability of NFL to calcium-dependent proteases (Zimmerman and Schaepfer, 1982;Vaidya et al, 2000). Moreover, NFL has been reported to be disassembled by phosphorylation through several kinases which seem to differ from those involved in NFM and NFH phosphorylation (Hashimoto et al, 1998;Veeranna et al, 1998;Al-Chalabi and Miller, 2003).…”

Changes in neurofilament protein‐immunoreactivity after kainic acid treatment of organotypic hippocampal slice cultures

“…In addition to the variations in the amounts of the NF proteins in pathological stages, phosporylation/dephosphorylation is thought to be one early sign in situations such as ischemia, seizures and traumatic brain injury (Kaku et al, 1993; Wang et al, 1994; Lee and Cleveland, 1996), and changes in dendrites preceding those in axons (Posmantur et al, 2000). In adult rats a shift of NF‐H from the phosphorylated to non‐phosphorylated form has been detected in many brain areas, including the hippocampus, as early as 1 day after KA injection in adult rats (Wang et al, 1994), and within days after seizures induced by chronic electroconvulsive treatment (Vaidya et al, 2000). Because we used antibodies that recognize phosporylation‐independent epitopes of the NF proteins, no conclusions can be drawn about the effect of KA on the phosphorylation/dephosphorylation of NF proteins in our slices.…”