Enhanced anxiety-like behavior induced by chronic neuropathic pain and related parvalbumin-positive neurons in male rats.

Anxiety commonly co-occurs with and exacerbates pain, but the interaction between pain progression and anxiety, and its underlying mechanisms remain unclear. Inhibitory interneurons play a crucial role in maintaining normal central nervous system function and are suggested to be involved in pain-induced anxiety. This study aimed to elucidate the time-dependent effects of neuropathic pain on the developmental anxiety-like behaviors and related inhibitory interneurons; parvalbumin (PV)- and cholecystokinin (CCK)-positive neurons in corticolimbic regions. Using an 8-week-old male Wistar rat model with partial sciatic nerve ligation (pSNL), anxiety-like behaviors were biweekly assessed post-surgery through open field (OF) and elevated plus maze (EPM) tests. From 4 weeks post-surgery, pSNL rats exhibited reduced OF center time, rearing, and initial activity, along with diminished EPM open-arm activities (time spent, head dips, movement, and rearing), which correlated with the paw withdrawal threshold. These effects were absent at 2 weeks post-surgery. At 8 weeks post-surgery, specific behaviors (decreased total rearing and increased inactive time in EPM) were observed in the pSNL group. Immunohistochemistry revealed changes in PV- and CCK-positive neurons in specific corticolimbic subregions of pSNL rats at 8 weeks post-surgery. Notably, PV-positive neuron densities in the basolateral amygdaloid complex (BLC) and hippocampal cornu ammonis areas 1 and 2 correlated with anxiety-like behavioral parameters. PV-positive neurons in the BLC of pSNL rats were predominantly changed in large-cell subtypes and were less activated. These findings indicate that anxiety-like behaviors emerge in the late phase of neuropathic pain and relate to PV-positive neurons in corticolimbic regions of pSNL rats.

Farnesylpyridinium, an analog of isoprenoid farnesol, induces apoptosis but suppresses apoptotic body formation in human promyelocytic leukemia cells.

1-Farnesylpyridinium (FPy), an analog of isoprenoid farnesol, initially induced morphological changes similar to those of typical apoptosis in human leukemia HL-60 cells but FPy-treated cells were characterized by the absolute absence of final apoptotic events such as fragmentation into apoptotic bodies. FPy-induced cell death was considered to be apoptotic on the basis of the induction of DNA fragmentation and the protection against these events by the coaddition of a pan-caspase inhibitor. The increase in the cytoplasmic cytochrome c level supported the possibility that FPy-treated cells should have the ability to complete the entire apoptotic process ending in cell fragmentation and apoptotic body formation. At concentrations too low to induce apoptosis, FPy could suppress the induction of apoptotic body formation in HL-60 cells by typical inducers of apoptosis such as actinomycin D or anisomycin. FPy exhibited a cytochalasin-like effect on spatial arrangement of actin filament independent of its apoptosis-inducing activity.