A comparison of neurodegeneration linked with neuroinflammation in different brain areas of rats after intracerebroventricular colchicine injection

Abstract

Colchicine induces neurodegeneration, but the extent of neurodegeneration in different areas of the brain in relation to neuroinflammation remains unclear. Such information may be useful to allow for the development of a model to compare colchicine-induced neurodegeneration with other neurodegenerative diseases such as Alzheimer's Disease (AD). The present study was designed to investigate the extent of neurodegeneration along with neuroinflammation in different areas of the brain, e.g. frontal cortex, parietal cortex, occipital cortex, corpus striatum, amygdala and hippocampus, in rats along with memory impairment 21 days after a single intracerebroventricular (icv) injection of colchicine. Memory parameters were measured before and after icv colchicine injection in all test groups of rats (control, sham-operated, colchicineinjected [ICIR] rats). On Day 21 post-injection, rats from all groups were anesthesized and tissues from the various brain areas were collected for assessment of biomarkers of neuroinflammation (i.e. levels of ROS, nitrite and proinflammatory cytokines TNF and IL-1) and neurodegeneration (assessed histologically). The single injection of colchicine resulted in impaired memory and neurodegeneration (significant presence of plaques, Nissl granule chromatolysis) in various brain areas (frontal cortex, amygdala, parietal cortex, corpus striatum), with maximum severity in the hippocampus. While IL-1, TNF, ROS and nitrite levels were altered in different brain areas in the ICIR rats, these parameters had their greatest change in the hippocampus. This study showed that icv injection of colchicine caused strong neurodegeneration and neuroinflammation in the hippocampus of rats and the increases in neurodegeneration were corroborated with those of neuroinflammation at the site. The present study also showed that the extent of neurodegeneration and neuroinflammation in different brain areas of the colchicine-injected rats were AD-like and supported the fact that such rats might have the ability to serve as a sporadic model of AD.

NMDA receptor is involved in neuroinflammation in intracerebroventricular colchicine-injected rats

“…Pro-inflammatory cytokines may increase NMDA-induced intracellular Ca 2+ increase by effects on astrocytes, microglia or glutamatergic neurons (Yoshiyama & Groat 2007). Sil et al (2015) reported that ICIR showed increased pro-inflammatory cytokines (TNF and IL-1) levels in different brain areas, indicating neuroinflammation in the brain. Soliven and Albert (1992) reported a dysregulation in Ca 2+ ion influx via NMDA receptor could produce an elevation in intracellular Ca 2+ ions and NO that, in turn, may initiate neuroinflammation in neuronal cells of the superior cervical ganglia.…”

“…Neuroinflammation has been proposed by several investigators as one of the causing factors for neurodegeneration in different chemically-induced animal models of AD, e.g. streptozotocin (STZ), okadaic acid and colchicine when injected intracerebroventricularly (icv) (Nazem et al 2015;Sil et al 2015). Sil et al (2014) reported that neurodegeneration in icv colchicineinjected rats was dependent on cyclooxygenase (COX)-induced neuroinflammation, as naproxen (non-specific COX blocker) could inhibit this neuroinflammation/degeneration.…”

Cox-2 Plays a Vital Role in the Impaired Anxiety Like Behavior in Colchicine Induced Rat Model of Alzheimer Disease

“…The neuropathology in cAD rats may not be exactly similar to AD as colchicine induces nonspecific neurodegeneration. Intracerebroventricular colchicine injected model of AD rats produced neurodegeneration and amyloid plaques in different parts of the brain which had similarity with the pattern of AD pathology [ 4 ]. The impairment of memory in colchicine induced AD rats also showed similarity with AD patients [ 14 – 24 ].…”

“…If the axoplasmic flow is blocked, it affects the normal activity of the neurons resulting in its death [ 1 , 2 ]. Intracerebroventricular injection of colchicine in the lateral ventricles of rat causes neurodegeneration in different brain areas including hippocampus and amygdala and as an outcome impairments of cognitive (e.g., memory) [ 3 , 4 ] and noncognitive (e.g., anxiety behavior) functions occur [ 5 ]. Raghavendra et al [ 6 ] have shown that cAD rats exhibit anxiogenic behavior in an elevated plus maze whereas Sil and Ghosh [ 5 ] have reported anxiolytic behavior in cAD rats in an elevated open field with a novel object in the centre along with lower level of serum corticosterone.…”

“…Sil et al [ 4 ] have indicated that the colchicine induced neurodegeneration was mediated by neuroinflammation. These investigators have also reported that colchicine induced anxiolytic behavior was due to cyclooxygenase (cox) induced neuroinflammation mediated neurodegeneration [ 4 , 5 , 7 ]. Moreover, it was also reported that the anxiolytic behavior along with neurodegeneration was increased in cAD rats in 3 weeks of study compared to that of 2 weeks of study [ 5 ].…”