Hippocampal neurogenesis modulated by Quinic acid: A therapeutic strategy for the neurodegenerative disorders.

Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders.

Nicotinic acid modulates microglial TREM-2 gene in Phytohaemagglutinin-Induced in vitro model of Alzheimer's disease like pathology.

Alzheimer's disease (AD) is a multifactorial,neurodegenerative disorder linked withextracellular amyloid beta (Aß) plaques deposition and formation of intracellular neurofibrillary tangles (NFTs). Currently, no effective therapies are available to cure AD. Neuroinflammation isa well-known hallmark in the onset and advancement of AD and triggering receptor expressed on myeloid cells-2 (TREM-2), a microglial gene, is responsible for regulating inflammatory responses and clearance of cellular debris. Loss of TREM-2functionincreases neuroinflammation associated expression of pro-inflammatory markersthus resultingin reduced clearance of Aß that further aid in disease progression.Therefore, targeting neuroinflammation is a good therapeutic approach for AD. This study aimed to determine the neuroprotective effect of nicotinic acid (NA) in vitro model of AD-like pathology induced in F-98 cell line using Phytohemagglutinin (PHA). MTT assay was employed for checking the cell viability as well as the proliferation of the cells following treatment with NA. PHA at the concentration of 10 µg/mL produces maximum plaques. The neuroprotective effect of NA was next evaluated against PHA-induced plaques and it was observed that NA reverses the damages induced by PHA i.e., by inhibiting the clustering of the cells and replacing the damaged cells with the new ones. Further, NA also increased the expression of TREM-2/DAP-12 with parallel decreased in the expression of IL-1ß, TNF-α and iNOS. It also successfully altered disease associated ADAM-10 and BACE-1 compared to PHA control. These findings suggest that NA might be considered as a good therapeutic candidate for the treatment of neurodegenerative disorders like AD.

In vivo anticonvulsant activity of 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine in pilocarpine and strychnine induced-seizure models.

An imbalance between inhibitory (GABA) and excitatory (Glutamate) neurotransmission contribute to the development of epilepsy. Earlier studies reported that dysregulation of GABA and glutamatergic activities resulted in status epilepticus (SE) and ultimately support the development of temporal lobe epilepsy (TLE), a type of resistant epilepsy. In the earlier work, 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine demonstrated anticonvulsant activity against pentylenetetrazole (PTZ)-induced seizures. Apart from the PTZ-induced TLE, the dysregulation muscaranic receptors and glycine receptors are also widely reported phenomena in the development of temporal lobe epilepsy. Keeping the role of these two receptors in epilepsy, the present work investigated the effect of 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine in pilocarpine-induced and strychnine-induced seizure models. Our results demonstrated that 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine significantly delayed the onset of seizure with maximum protection from SE in pilocarpine-induced seizure model. However, the test compound did not revealed any effect on strychnine-induced seizures in mice. Based on these observations, we suggest that 2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine could be a potential candidate in reduction of SE and treatment of temporal lobe epilepsy (TLE) in future.