Inflammation: A new candidate in modulating adult neurogenesis

Abstract

Any pathological perturbation to the brain provokes a cascade of molecular and cellular events, which manifests in the form of microglial activation and release of various proinflammatory molecules. This eventually culminates in a profound neuroinflammatory reaction that characterizes the brain's response to stress, injury, or infection. The inflammatory cascade is an attempt by the system to eliminate the challenge imposed on the brain, clear the system of the dead and damaged neurons, and rescue the normal functioning of this vital organ. However, during the process of microglial activation, the proinflammatory mediators released exert certain detrimental effects, and neural stem cells and progenitor cells are likely to be affected. Here we review how the proliferation, maturation, and migration of the neural stem cells are modulated under such an inflammatory condition. The fate of the noncommitted neural stem cells and its differentiation potency are often under strict regulation, and these proinflammatory mediators seem to disrupt this critical balance and finely tune the neurogenesis pattern in the two niches of neurogenesis, the subventricular zone and the subgranular zone of the hippocampus. Moreover, the migration ability of these stem cells, which is important for localization to the proper site, is also affected in a major way by the chemokines released following inflammation.

Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

“…In normal conditions it promotes and regulates neurogenesis [61], plays a role in hippocampal development [29], and is essential to learning and memory formation [28,62] (Figure 2, Table 1). This complex and divergent role of TNF-α is mediated is required for cognition at moderate levels by aiding hippocampal development and synaptic signalling.…”

Changes in Cyclooxygenase-2 Immunoreactivity in the Hippocampus in a Model of Streptozotocin-Induced Type 1 Diabetic Rats

“…Both isoenzymes convert arachidonic acid into multifunctional prostanoids. COX-2 enzyme is reported as a key player [11] in neuro-inflammation which is involved in most neurodegenerative disorders by eliciting neuronal death and influencing formation of new neurons [9]. In several tissues, mRNA level of COX-2 was studied and level in the brain was lowest [24], but its expression in brain was not the lowest [35].…”

1980-2011: Parkinson's Disease and Advance in Stem Cell Research

“…Recent data have also supported the idea that a reduction in the levels of anti-inflammatory factors itself can further enhance vulnerability of dopaminergic neurons to apoptosis in a neurodegenerative environment (Barnum and Tansey, 2010;Lu et al, 2010;Maguire-Zeiss and Federoff, 2010). Furthermore, it has been recently suggested that pro-inflammatory cytokines exert a negative impact on neuronal differentiation, while anti-inflammatory cytokines facilitate neurogenesis (Mathieu et al, 2010) and neuronal migration towards appropriate targets (Das and Basu, 2008). These data clearly indicate that pro-and antiinflammatory responses must be strictly balanced to prevent the potential detrimental effects of prolonged or unregulated inflammation on vulnerable neuronal populations .…”