A Mild Dose of Aspirin Promotes Hippocampal Neurogenesis and Working Memory in Experimental Ageing Mice.

Aspirin has been reported to prevent memory decline in the elderly population. Adult neurogenesis in the hippocampus has been recognized as an underlying basis of learning and memory. This study investigated the effect of aspirin on spatial memory in correlation with the regulation of hippocampal neurogenesis and microglia in the brains of ageing experimental mice. Results from the novel object recognition (NOR) test, Morris water maze (MWM), and cued radial arm maze (cued RAM) revealed that aspirin treatment enhances working memory in experimental mice. Further, the co-immunohistochemical assessments on the brain sections indicated an increased number of doublecortin (DCX)-positive immature neurons and bromodeoxyuridine (BrdU)/neuronal nuclei (NeuN) double-positive newly generated neurons in the hippocampi of mice in the aspirin-treated group compared to the control group. Moreover, a reduced number of ionized calcium-binding adaptor molecule (Iba)-1-positive microglial cells was evident in the hippocampus of aspirin-treated animals. Recently, enhanced activity of acetylcholinesterase (AChE) in circulation has been identified as an indicative biomarker of dementia. The biochemical assessment in the blood of aspirin-treated mice showed decreased activity of AChE in comparison with that of the control group. Results from this study revealed that aspirin facilitates hippocampal neurogenesis which might be linked to enhanced working memory.

Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder.

Elevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the histamine-2 receptors in parietal cells, thereby reducing the production of HCl in the stomach. While some reports indicate the neuroprotective effects of ranitidine, its role against GI disorder-related anxiety remains unclear. Therefore, we investigated the effect of ranitidine against anxiety-related behaviors in association with changes in neuronal density in the hippocampal cornu ammonis (CA)-3 region of cysteamine hydrochloride-induced mouse model of GI disorder. Results obtained from the open field test (OFT), light and dark box test (LDBT), and elevated plus maze (EPM) test revealed that ranitidine treatment reduces anxiety-like behaviors in experimental animals. Nissl staining and immunohistochemical assessment of ionized calcium-binding adapter molecule (Iba)-1 positive microglia in cryosectioned brains indicated enhanced density of pyramidal neurons and reduced activation of microglia in the hippocampal CA-3 region of brains of ranitidine-treated experimental mice. Therefore, this study suggests that ranitidine mediates anxiolytic effects, which can be translated to establish a pharmacological regime to ameliorate anxiety-related symptoms in humans.

Omeprazole treatment manifests anxiolytic effects in a cysteamine hydrochloride induced mouse model of gastrointestinal disorder.

Omeprazole, a proton pump inhibitor (PPI), has widely been used to treat various gastrointestinal (GI) disorders. Notably, many clinical symptoms of GI disorders have been known to be associated with anxiety. In recent years, an exponentially increased number of subjects with abnormal ageing, neurological deficits, and psychiatric problems simultaneously exhibit GI dysfunctions as well as anxiety. Considering the fact, drugs that are used to treat GI disorders can be speculated to mitigate anxiety-related symptoms, and vice versa. Although, omeprazole treatment has been reported to result in development of anxiety and neurocognitive decline, ample reports suggest that omeprazole treatment is beneficial for the positive regulation of neuroplasticity. While underlying mechanisms of omeprazole-mediated neurological alterations remain obscure, the available scientific data on the omeprazole induced adverse effects in the brain appear to be inadequate, uncertain, and controversial. Hence, this study revisited the effect of omeprazole treatment on the degree of anxiety-like behaviours in a cysteamine hydrochloride (HCl) induced mouse model of GI disorder using open field test (OFT), light-dark box (LDB) test and elevated plus maze (EPM). Results revealed that omeprazole treatment mitigates anxiety-related behaviours in the cysteamine HCl induced animal model of GI disorder. Thus, this study assuredly supports and validates the anxiolytic properties of omeprazole. However, the adverse effects associated with inappropriate intake of omeprazole may not completely be excluded. Therefore, this study advocates the future direction in determining the long-term effects of omeprazole on the brain functions.

Cell cycle re-entry of neurons and reactive neuroblastosis in Huntington's disease: Possibilities for neural-glial transition in the brain.

Huntington's disease (HD) is an autosomal dominant pathogenic condition that causes progressive degeneration of GABAergic neurons in the brain. The abnormal expansion of the CAG repeats in the exon 1 of the Huntingtin gene (HTT gene) has been associated with the onset and progression of movement disorders, psychiatric disturbance and cognitive decline in HD. Microglial activation and reactive astrogliosis have been recognized as the key pathogenic cellular events in the brains of HD subjects. Besides, HD has been characterized by induced quiescence of neural stem cells (NSCs), reactive neuroblastosis and reduced survival of newborn neurons in the brain. Strikingly, the expression of the mutant HTT gene has been reported to induce the cell cycle re-entry of neurons in HD brains. However, the underlying basis for the induction of cell cycle in neurons and the fate of dedifferentiating neurons in the pathological brain remain largely unknown. Thus, this review article revisits the reports on the regulation of key signaling pathways responsible for altered cell cycle events in diseased brains, with special reference to HD and postulates the occurrence of reactive neuroblastosis as a consequential cellular event of dedifferentiation of neurons. Meanwhile, a substantial number of studies indicate that many neuropathogenic events are associated with the expression of potential glial cell markers by neuroblasts. Taken together, this article represents a hypothesis that transdifferentiation of neurons into glial cells might be highly possible through the transient generation of reactive neuroblasts in the brain upon certain pathological conditions.