Intranigral Injection of Endotoxin Suppresses Proliferation of Hippocampal Progenitor Cells

Abstract

Brain inflammation can result in functional disorders observed in several neurodegenerative diseases and that can be also associated with reduced neurogenesis. In this study, we investigate the effect of mild inflammation, induced by unilateral injection of Endotoxin (ET) in the substantia nigra (SN)/Ventral Tegmental Area, on the proliferation and survival of stem/progenitor cells in the dentate gyrus (DG) of the hippocampus. Adult female rats received unilateral injection of ET (2 μg/2 μl saline) or sterile saline (2 μl) in the right SN followed by 5′-Bromo-2′-deoxyuridine (BrdU) injections (66 mg/kg/injection). Intranigral ET injection induced bilateral decrease in the number of newly born BrdU positive cells in the DG. This effect was paralleled by a significant decrease in the exploratory behavior of rats, as assessed by the Y-maze novel arm exploration task. ET also induced a transient decrease in the number of tyrosine hydroxylase-positive cells in the injected SN, impaired motor behavior, and caused microglial activation in the SN. This study provides an experimental simulation of the remote effects of moderate and reversible neuroinflammation resulting in impaired communication between midbrain dopaminergic neurons and the hippocampus.

Urinary Tract Infections Impair Adult Hippocampal Neurogenesis

“…This effect is further manifested a month post infection as a decrease in the number of BrdU/NeuN double-positive cells and thus decreased adult hippocampal neurogenesis. This finding is in line with accumulated evidence showing a causal link between decreased neurogenesis and neuroinflammation [ 4 , 5 , 12 , 13 ] or peripheral inflammation in general [ 10 , 39 ]. In addition to decreased proliferation of NSCs, we also detected a decrease in the mRNA expression of Bdnf , Ngf , and Fgf2 in the hippocampus of rats with a UTI.…”

“…One of the most intriguing characteristics of hippocampal neurogenesis is that it is highly prone to changes in response to a variety of intrinsic and extrinsic factors [ 3 ]. Among these factors, inflammation, whether general or localized in the brain (neuroinflammation), is a well-known strong suppressor of adult hippocampal neurogenesis [ 4 , 5 , 6 ]. The brain has been previously assumed as an immune-privileged organ.…”

Role of Neuroinflammation in the Establishment of the Neurogenic Microenvironment in Brain Diseases

“…The first evidence that inflammation negatively regulates neurogenesis is reported by Ekdahl et al [49] that a 4-week long intrahippocampal infusion of LPS strongly impairs basal hippocampal neurogenesis in adult rats, which could be ameliorated by treatment with microglial inhibitor minocycline. This finding was shortly confirmed in rats treated with LPS via different routes, including systemic [50], intrastriatal [51], intracerebroventricular [52], and intranigral [53]. Given that neuroinflammation and cognitive deficits are commonly present in major neurological disorders, there is growing interest in deciphering the molecular mechanisms by which neuroinflammation modulates NSC behaviors.…”

Long COVID in K18-hACE2 mice causes persistent brain inflammation and cognitive impairment

“…More specifically, studies involving repeated exposure to silicon dioxide nanoparticles, which produce inflammation, endotoxin induced nigrostriatal damage , and maternal immune activation, using poly(I:C) reported attenuation of Y maze exploration. 38,39,40,41 Maternal immune activation also elevated anxiety measures. 40 Additional research is needed to differentiate between the general effects of infection-induced immune activation and the specific mechanism associated with SARS-CoV-2 infection.…”