Aqueous Leaf Extract of Withania somnifera as a Potential Neuroprotective Agent in Sleep-deprived Rats: a Mechanistic Study Shaffi Manchanda 1 & Rachana Mishra 1 & Rumani Singh 2 & Taranjeet Kaur 1 & Gurcharan Kaur 1 Received: 10 December 2015 /Accepted: 22 March 2016 # Springer Science+Business Media New York 2016 Abstract Modern lifestyle and sustained stress of profession- al commitments in the current societal set up often disrupts the normal sleep cycle and duration which is known to lead to cognitive impairments. In the present study, we report whether leaf extract of Withania somnifera (Ashwagandha) has poten- tial neuroprotective role in acute stress of sleep deprivation. Experiments were performed on three groups of adult Wistar rats: group 1 (vehicle treated-undisturbed sleep [VUD]), group 2 (vehicle treated-sleep deprived [VSD]), and group 3 (ASH-WEX treated-sleep deprived [WSD]). Groups 1 and 2 received single oral feeding of vehicle and group 3 received ASH-WEX orally (140 mg/kg or 1 ml/250 g of body weight) for 15 consecutive days. Immediately after this regimen, ani- mals from group 1 were allowed undisturbed sleep (between 6 a.m. and 6 p.m.), whereas rats of groups 2 and 3 were deprived of sleep during this period. We observed that WSD rats showed significant improvement in their performance in be- havioral tests as compared to VSD group. At the molecular level, VSD rats showed acute change in the expression of proteins involved in synaptic plasticity, cell survival, and ap- optosis in the hippocampus region of brain, which was sup- pressed by ASH-WEX treatment thus indicating decreased cellular stress and apoptosis in WSD group. This data suggest that Ashwagandha may be a potential agent to suppress the acute effects of sleep loss on learning and memory impairments and may emerge as a novel supplement to control SD-induced cognitive impairments. Keywords Ashwagandha . Neuroprotection . Sleep deprivation . Synaptic plasticity . Cell survival Introduction Sleep has a crucial role in the maintenance of physical and mental health of mammalian body. Disruptions in the duration and quality of sleep leads to an array of metabolic, physical, and cognitive disturbances which give birth to conditions like anxi- ety, stress, obesity, and compromised decision-making skills among others. Sleep as a physiological and two-stage phenom- enon in consolidation of both declarative and non-declarative memories strengthens cognitive domain of the body [1, 2], and sleep abatement or sleep loss results in neurocognitive dysfunc- tions and reduced daytime vigilance. Total sleep deprivation affects almost every essential function of the body in one or another way, but some brain regions associated with memory and perception are affected to such levels that their sleep- dependent functions are demolished. Such brain regions are the hippocampus and pyriform cortex. The hippocampus is the key brain region for the induction and subsequent maintenance of sleep-dependent long-term potentiation (LTP) and long-term depression (LTD) through the modulation of synaptic activity. Various studies in rodents have reported that both shorter and longer periods of sleep restriction impair LTP maintenance de- spite of the method being used for sleep fragmentation [3–6]. In traditional system of medicine Ayurveda, Withania somnifera (Ashwagandha) is classified as a rasayana herb that works in a global manner to promote health and increase lon- gevity. The plant species is attributed to have sedative properties as per the name of the species “somnifera” meaning sleep * Gurcharan Kaur kgurcharan.neuro@yahoo.com 1 Medical Biotechnology Laboratory, Department of Biotechnology, Guru Nanak Dev University, Amritsar 143005, Punjab, India 2 Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA Mol Neurobiol DOI 10.1007/s12035-016-9883-5