Sustained Activation of the Anterior Thalamic Neurons with Low Doses of Kainic Acid Boosts Hippocampal Neurogenesis.

Adult hippocampal neurogenesis is prone to modulation by several intrinsic and extrinsic factors. The anterior nucleus (AN) of the thalamus has extensive connections with the hippocampus, and stimulation of this region may play a role in altering neurogenesis. We have previously shown that electrical stimulation of the AN can substantially boost hippocampal neurogenesis in adult rats. Here, we performed selective unilateral chemical excitation of the cell bodies of the AN as it offers a more specific and sustained stimulation when compared to electrical stimulation. Our aim is to investigate the long-term effects of KA stimulation of the AN on baseline hippocampal proliferation of neural stem cells and neurogenesis. Continuous micro-perfusion of very low doses of kainic acid (KA) was administered into the right AN for seven days. Afterwards, adult male rats received 5'-bromo-2'-deoxyuridine (BrdU) injections (200 mg/kg, i.p) and were euthanized at either one week or four weeks post micro-perfusion. Open field and Y-maze tests were performed before euthanasia. The KA stimulation of the AN evoked sustained hippocampal neurogenesis that was associated with improved spatial memory in the Y-maze test. Administering dexamethasone prior to and simultaneously with the KA stimulation decreased both the hippocampal neurogenesis and the improved spatial recognition memory previously seen in the Y-maze test. These results suggest that hippocampal neurogenesis may be a downstream effect of stimulation in general, and of excitation of the cell bodies of the AN in particular, and that stimulation of that area improves spatial memory in rats.

Urinary Tract Infections Impair Adult Hippocampal Neurogenesis.

Previous studies have suggested a link between urinary tract infections (UTIs) and cognitive impairment. One possible contributing factor for UTI-induced cognitive changes that has not yet been investigated is a potential alteration in hippocampal neurogenesis. In this study, we aim to investigate the effect of UTI on brain plasticity by specifically examining alterations in neurogenesis. Adult male Sprague Dawley rats received an intra-urethral injection of an Escherichia coli (E. coli) clinical isolate (108 CFU/mL). We found that rats with a UTI (CFU/mL ≥ 105) had reduced proliferation of neural stem cells (NSCs) at an early time point post infection (day 4) and neurogenesis at a later time point (day 34). This was associated with the decreased expression in mRNA of BDNF, NGF, and FGF2, and elevated expression of IL-1ß in the hippocampus at 6 h post infection, but with no changes in optical intensity of the microglia and astrocytes. In addition, infected rats spent less time exploring a novel arm in the Y-maze test. Treatment with an anti-inflammatory drug did not revert the effect on NSCs, while treatment with antibiotics further decreased the basal level of their proliferation. This study presents novel findings on the impact of urinary tract infections on hippocampal neurogenesis that could be correlated with cognitive impairment.

Long-term stimulation of the anteromedial thalamus increases hippocampal neurogenesis and spatial reference memory in adult rats.

Deep brain stimulation (DBS) has shown positive clinical results in neurodegenerative diseases. Previous work from our group showed that a single session of DBS to the anteromedial thalamic nucleus (AMN) in awake rats, increased proliferation of stem/progenitor cells in the dentate gyrus (DG) of the hippocampus. We thought to examine the effect of single versus multiple sessions of DBS to the AMN in modulating adult hippocampal neurogenesis. Rats received unilateral single session, multiple sessions or no electrical stimulation (sham) in the right AMN. Rats received 5'-bromo-2'-deoxyuridine (BrdU) injections and were followed over a period of 1 week or 4 weeks. Single session of electrical stimulation induced a 1.9-fold increase in the number of proliferating BrdU positive cells after one week from stimulation and a 1.8-fold increase at four weeks post stimulation, both in the ipsilateral DG. As for multiple sessions of stimulation, they induced a 3- fold increase that extended to the contralateral DG after 4 weeks from stimulation. Spatial reference memory was tested in the Y-maze test by examining novel arm exploration. Both single and multiple sessions of stimulation prompted an increase in novel arm exploration at week 4, while only the multiple sessions of stimulation had this effect starting from week 1. This study demonstrates that sustained activation of the AMN boosts neurogenesis and improves spatial reference memory.

PTSD in the COVID-19 Era.

BACKGROUND: In December 2019, Wuhan City in Hubei Province, China witnessed an outbreak of a novel type of coronavirus (COVID-19), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The sharp rise in the number of infected cases and the surge spike in fatalities worldwide prompted the World Health Organization (WHO) to declare this rapid outbreak a global pandemic in March 2020. The economic, health, and social ramifications of COVID-19 induced fear and anxiety all over the world. OBJECTIVE: The purpose of this review is to discuss how precautionary measures and restrictions imposed by governments, such as quarantines, lockdowns, and social distancing, have not only caused economic losses, but also a rise in mental health problems specifically post-traumatic stress disorder (PTSD). METHODS: A deep comprehensive review of the relevant literature regarding the pandemic and its debilitating consequences on the psychological status of the public was performed. RESULTS: This review illustrates that the pandemic had a traumatic impact on the psychological functioning of the public, particularly COVID-19 survivors, older adults, and healthcare workers, due to difficulties in coping with new realities and uncertainties. CONCLUSION: In this review, we have discussed the psychological implications of this pandemic and we have provided an extensive background for understanding options regarding PTSD management in healthy individuals and those with preexisting conditions.

Stem Cells: In Sickness and in Health.

Stem cells are undifferentiated cells with the ability to proliferate and convert to different types of differentiated cells that make up the various tissues and organs in the body. They exist both in embryos as pluripotent stem cells that can differentiate into the three germ layers and as multipotent or unipotent stem cells in adult tissues to aid in repair and homeostasis. Perturbations in these cells' normal functions can give rise to a wide variety of diseases. In this review, we discuss the origin of different stem cell types, their properties and characteristics, their role in tissue homeostasis, current research, and their potential applications in various life-threatening diseases. We focus on neural stem cells, their role in neurogenesis and how they can be exploited to treat diseases of the brain including neurodegenerative diseases and cancer. Next, we explore current research in Induced Pluripotent Stem Cells (iPSC) techniques and their clinical applications in regenerative and personalized medicine. Lastly, we tackle a special type of stem cells called Cancer Stem Cells (CSCs) and how they can be responsible for therapy resistance and tumor recurrence and explore ways to target them.

Role of MicroRNAs in Anesthesia-Induced Neurotoxicity in Animal Models and Neuronal Cultures: a Systematic Review.

Exposure to anesthetic agents in early childhood or late intrauterine life might be associated with neurotoxicity and long-term neurocognitive decline in adulthood. This could be attributed to induction of neuroapoptosis and inhibition of neurogenesis by several mechanisms, with a pivotal role of microRNAs in this milieu. MicroRNAs are critical regulators of gene expression that are differentially expressed in response to internal and external environmental stimuli, including general anesthetics. Through this systematic review, we aimed at summarizing the current knowledge apropos of the roles and implications of deregulated microRNAs pertaining to anesthesia-induced neurotoxicity in animal models and derived neuronal cultures. OVID/Medline and PubMed databases were lastly searched on April 1st, 2019, using the Medical Subject Heading (MeSH) or Title/Abstract words ("microRNA" and "anesthesia"), to identify all published research studies on microRNAs and anesthesia. During the review process, data abstraction and methodological assessment was done by independent groups of reviewers. In total, 29 studies were recognized to be eligible and were thus involved in this systematic review. Anesthetic agents studied included sevoflurane, isoflurane, propofol, bupivacaine, and ketamine. More than 40 microRNAs were identified to have regulatory roles in anesthesia-induced neurotoxicity. This field of study still comprises several gaps that should be filled by conducting basic, clinical, and translational research in the future to decipher the exact role of microRNAs and their functions in the context of anesthesia-induced neurotoxicity.

Intranigral Injection of Endotoxin Suppresses Proliferation of Hippocampal Progenitor Cells.

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.

Intracerebroventricular injections of endotoxin (ET) reduces hippocampal neurogenesis.

Physio-pathological conditions such as neuroinflammation can modulate neurogenesis in the hippocampus. The aim of this study is to follow the time course of inflammation-induced effects on the neurogenic niche and the counter-effects of an anti-inflammatory drug. Rats received intracerebroventricular injections of lipopolysaccharide/endotoxin (ET) and intraperitoneal injections of 5'-bromo-2'-deoxyuridine, then perfused at different time intervals. At day 3, ET injection resulted in thermal hyperalgesia accompanied by a significant decrease in neurogenesis. A rebound of neurogenesis was detected at day 6 and levels were back to basal at day 9. Daily treatment with Piroxicam alleviated the ET-induced effects.

Modeling Human Neurological and Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Neuronal Differentiation and Its Applications in Neurotrauma.

With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine. They further aid in the development of regenerative medicine, autologous cell therapy and drug or toxicity screening. Here, we provide a comprehensive overview of the recent development in the field of iPSCs research, specifically for modeling human neurological and neurodegenerative diseases, and its applications in neurotrauma. These are mainly characterized by progressive functional or structural neuronal loss rendering them extremely challenging to manage. Many of these diseases, including Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) have been explored in vitro. The main purpose is to generate patient-specific iPS cell lines from the somatic cells that carry mutations or genetic instabilities for the aim of studying their differentiation potential and behavior. This new technology will pave the way for future development in the field of stem cell research anticipating its use in clinical settings and in regenerative medicine in order to treat various human diseases, including neurological and neurodegenerative diseases.