CRISPR: a tool with potential for genomic reprogramming in neurological disorders.

The intricate neural circuitry of the brain necessitates precise and synchronized transcriptional programs. Any disturbance during embryonic or adult development, whether caused by genetic or environmental factors, may result in refractory and recurrent neurological disorders. Inadequate knowledge of the pathogenic mechanisms underlying neurological disorders is the primary obstacle to the development of effective treatments, necessitating the development of alternative therapeutic approaches to identify rational molecular targets. Recently, with the evolution of CRISPR-Cas9 technology, an engineered RNA system provides precise and highly effective correction or silencing of disease-causing mutations by modulating expression and thereby avoiding the limitations of the RNA interference strategy. This article discusses the CRISPR-Cas9 technology, its mechanisms, and the limitations of the new technology. We provide a glimpse of how the far-reaching implications of CRISPR can open new avenues for the development of tools to combat neurological disorders, as well as a review of recent attempts by neuroscientists to launch therapeutic correction.

Cellular demolition: Proteins as molecular players of programmed cell death.

Apoptosis, a well-characterized and regulated cell death programme in eukaryotes plays a fundamental role in developing or later-life periods to dispose of unwanted cells to maintain typical tissue architecture, homeostasis in a spatiotemporal manner. This silent cellular death occurs without affecting any neighboring cells/tissue and avoids triggering of immunological response. Furthermore, diminished forms of apoptosis result in cancer and autoimmune diseases, whereas unregulated apoptosis may also lead to the development of a myriad of neurodegenerative diseases. Unraveling the mechanistic events in depth will provide new insights into understanding physiological control of apoptosis, pathological consequences of abnormal apoptosis and development of novel therapeutics for diseases. Here we provide a brief overview of molecular players of programmed cell death with discussion on the role of caspases, modifications, ubiquitylation in apoptosis, removal of the apoptotic body and its relevance to diseases.

Slow Physical Growth, Delayed Reflex Ontogeny, and Permanent Behavioral as Well as Cognitive Impairments in Rats Following Intra-generational Protein Malnutrition.

Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed.