Amyloid ß lowering and cognition enhancing effects of ghrelin receptor analog [D-Lys (3)] GHRP-6 in rat model of obesity.

Obesity arising due to the dietary and life style changes is fast reaching epidemic proportions all over the world. There is increasing evidence that the incidence of Alzheimer disease (AD) is significantly influenced by a cluster of metabolic diseases, including diabetes and obesity. This study was aimed to test the suitability of experimentally-induced obesity in rats as an experimental animal model of AD. We used the procedure of neonatal administration of rats with monosodium L-glutamate (MSG), which generates adult obese animals as our study design and assessed the AD-like changes by measuring amyloid ß (1-42) and acetylcholinesterase (AChE) levels in the hippocampal extracts and cognitive impairments by Barnes maze task. Further, we investigated the influence of anti-obesity substance [D-Lys (3)] GHRP-6 on blood glucose, hippocampal Aß, AChE levels and restoration of cognitive deficits. Results revealed that administration of MSG to neonatal rats exhibited increased body mass index and serum glucose levels over the controls. Measurement of markers for AD-like molecular changes i.e. amyloid ß (Aß) and AChE levels showed marked elevation in these two parameters in the hippocampus of MSG-treated rats. Assessment of cognitive abilities by Barnes maze revealed spatial disorientation characteristic of AD. Administration of ghrelin receptor analog [D-Lys (3)] GHRP-6 to obese rats resulted in significant restoration of serum cholesterol, glucose, leptin and ghrelin levels to that of control with concomitant reduction in hippocampal Aß and AChE levels. In addition, the treated animals exhibited marked improvement in Barne’s maze task. These findings suggest that MSG-induced obese rats may serve as non-transgenic animal model for AD research. Further, the results indicate the potential of [D-Lys (3)] GHRP-6 as a promising anti-Alzheimer candidate.

Olfactory tract transection in neonatal rats: Evidence for Mitral cell regeneration and restoration of functional connectivity with its targets.

Central Nervous System (CNS) regeneration and repair mechanism are two important aspects of functional recovery in the adult central nervous system following brain and spinal cord injury. Following olfactory tract transection in neonatal rats, functional connectivity between the olfactory bulb and the piriform cortex gets re-established by 120 days. The recovery of the dendritic morphology was associated with the synchronized oscillatory activity between olfactory bulb and piriform cortex. Mitral cells which were regenerated after the transection showed profuse branching, indicative of their undifferentiated state. However, normal dendritic morphology could be seen by 120 days after olfactory tract transection. These results thus provide a supportive evidence for the restoration of the functional connections between the olfactory bulb and the piriform cortex at 120 days.