The effects of acetyl-11-keto-β-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats.

Enriched environment effect on Lipopolysaccharide-induced spatial learning, memory impairment and hippocampal inflammatory cytokine levels in male rats

Isolation, culture, and downstream characterization of primary microglia and astrocytes from adult rodent brain and spinal cord

Object recognition (OR) and the Morris water maze (MWM) are classical tasks widely used to assess memory parameters and deficits in rodents. Learning processes in both tasks involve integrity of the hippocampus and associated regions, and prefrontal cortex connections. Here, we highlight the idea that these classical tests can be used to indicate memory deficits caused by models of disease that affect hippocampal function in rats, and identify some practical issues of OR and MWM, based on the literature and our experience. Additionally, we have shown that the performance of both tasks does not alter blood levels of corticosterone, considering exposure to a single task. Hence, taking into consideration the difficulties and care required during task execution, the infrastructure needed and the training of the experimenter, we suggest that OR and its variations offer minimal manageable stressful conditions, representing an effective and practical tool for hippocampal-related memory assessment of rats. Thus, OR may provide similar information to that of the MWM, despite controversy regarding hippocampus participation in OR and given due differences in the types of memory evaluated and researchers' objectives. We recommend the observation of some important precautions and details, also based on the literature and our own experience.

Object recognition and Morris water maze to detect cognitive impairment from mild hippocampal damage in rats: A reflection based on the literature and experience.

The continuous generation of new neurons occurs in at least two well-defined niches in the adult rodent brain. One of these areas is the subgranular zone of the dentate gyrus (DG) in the hippocampus. While the DG is associated with contextual and spatial learning and memory, hippocampal neurogenesis is necessary for pattern separation. Hippocampal neurogenesis begins with the activation of neural stem cells and culminates with the maturation and functional integration of a portion of the newly generated glutamatergic neurons into the hippocampal circuits. The neurogenic process is continuously modulated by intrinsic factors, one of which is neuroinflammation. The administration of lipopolysaccharide (LPS) has been widely used as a model of neuroinflammation and has yielded a body of evidence for unveiling the detrimental impact of inflammation upon the neurogenic process. This work aims to provide a comprehensive overview of the current knowledge on the effects of the systemic and central administration of LPS upon the different stages of neurogenesis and discuss their effects at the molecular, cellular, and behavioral levels.

Adult hippocampal neurogenesis in the context of lipopolysaccharide-induced neuroinflammation: A molecular, cellular and behavioral review.

Astrocyte culture models: Molecular and function characterization of primary culture, immortalized astrocytes and C6 glioma cells.

Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling.

One of the changes found in the brain in Alzheimer's disease (AD) is increased calpain, derived from calcium dysregulation, oxidative stress, and/or neuroinflammation, which are all assumed to be basic pillars in neurodegenerative diseases. The role of calpain in synaptic plasticity, neuronal death, and AD has been discussed in some reviews. However, astrocytic calpain changes sometimes appear to be secondary and consequent to neuronal damage in AD. Herein, we explore the possibility of calpain-mediated astroglial reactivity in AD, both preceding and during the amyloid phase. We discuss the types of brain calpains but focus the review on calpains 1 and 2 and some important targets in astrocytes. We address the signaling involved in controlling calpain expression, mainly involving p38/mitogen-activated protein kinase and calcineurin, as well as how calpain regulates the expression of proteins involved in astroglial reactivity through calcineurin and cyclin-dependent kinase 5. Throughout the text, we have tried to provide evidence of the connection between the alterations caused by calpain and the metabolic changes associated with AD. In addition, we discuss the possibility that calpain mediates amyloid-β clearance in astrocytes, as opposed to amyloid-β accumulation in neurons.

Calpain-Mediated Alterations in Astrocytes Before and During Amyloid Chaos in Alzheimer's Disease.

Astrocytes, the most abundant glial cells, have several metabolic functions, including ionic, neurotransmitter and energetic homeostasis for neuronal activity. Reactive astrocytes and their dysfunction have been associated with several brain disorders, including the epileptogenic process. Glial Fibrillary Acidic Protein (GFAP) and S100 calcium-binding protein B (S100B) are astrocyte biomarkers associated with brain injury. We hypothesize that arundic acid (ONO-2506), which is known as an inhibitor of S100B synthesis and secretion, protects the hippocampal tissue from neuroinflammation and astrocyte dysfunction after status epileptics (SE) induction by Li-pilocarpine in young rats. Herein, we investigated the effects of arundic acid treatment, at time points of 6 or 24 h after the induction of SE by Li-pilocarpine, in young rats. In SE animals, arundic acid was able to prevent the damage induced by Li-pilocarpine in the hippocampus, decreasing neuroinflammatory signaling (reducing IL-1β, COX2, TLR4 and RAGE contents), astrogliosis (decreasing GFAP and S100B) and astrocytic dysfunction (recovering levels of GSH, glutamine synthetase and connexin-43). Furthermore, arundic acid improved glucose metabolism and reduced the glutamate excitotoxicity found in epilepsy. Our data reinforce the role of astrocytes in epileptogenesis development and the neuroprotective role of arundic acid, which modulates astrocyte function and neuroinflammation in SE animals. 

Jéssica Taday

Papers

Astrocyte culture models: Molecular and function characterization of primary culture, immortalized astrocytes and C6 glioma cells.

Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling.

Calpain-Mediated Alterations in Astrocytes Before and During Amyloid Chaos in Alzheimer's Disease.

Arundic acid (ONO-2506) downregulates neuroinflammation and astrocyte dysfunction after status epilepticus in young rats induced by Li-pilocarpine