Long-term depression induction and maintenance across regions of the apical branch of CA1 dendrites.

Well known as the center for learning and memory, hippocampus is the crucial brain region to study synaptic plasticity in the context of cellular fundamental mechanisms such as long-term depression (LTD) and long-term potentiation (LTP). However, despite years of extensive research, the key to our LTD queries and their induction mechanisms has not been fully understood. Previously, we reported the induction of late-LTD (L-LTD) in the distally located synapses of apical branch of hippocampal CA1 dendrites using strong low-frequency stimulation (SLFS). In contrast synapses at the proximal site could not express L-LTD. Thus, in the present study, we wanted to investigate whether or not synapses of apical dendritic branch at the proximal location could induce and maintain LTD and its related properties in in vitro rat hippocampal slices. Results indicated that the SLFS in the distal and proximal region triggered the plasticity related proteins (PRP) synthesis in both regions, as evident by the induction and maintenance of L-LTD in the distal region by virtue of synaptic and cross-tagging. In addition, the application of emetine at the time of proximal input stimulation prevented the transition of early-LTD (E-LTD) into L-LTD at the distal region, proving PRP synthesis at the proximal site. Further, it was observed that weak low-frequency stimulation (WLFS) could induce E-LTD in the proximal region along with LTD-specific tag-setting at the synapses. In conclusion, the current study suggests unique findings that the synaptic and cross-tagging mediate L-LTD expression is maintained in the proximal location of hippocampus apical CA1 dendrites.

Behavioural tagging: Effect of novelty exploration on plasticity related molecular signatures.

Learning and memory are one of those frontier areas of neurobiology which attract us to investigate the intricacy of this process. Here, we aimed to investigate the general mechanism of "Behavioural Tagging and Capture" in long term memory (LTM) formation and to find the key factors playing role in consolidation of LTM. In this study, we've shown that not only plasticity related proteins (PRPs) but neurotransmitters and immediate early genes (IEGs) also play an important role in memory formation process. It's very well evident that memory traces can last longer if close in time novelty is introduced around memory encoding. Here our results point out that this novelty exploration acts as a modulator in memory consolidation by providing PRPs such as brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), enhancing neurotransmitters (Dopamine), IEGs (cFos) and some enzymes such as acetylcholinesterase (AChE), monoamine oxidase (MAO), sodium-potassium ATPase (Na+K+-ATPase). Therefore, by using a Novel Object Recognition task (NOR) in combination with novel task exposure, we evaluated the role of molecular markers in memory consolidation employing a behavioural tagging model. The purpose of the current study was first to evaluate the effect of novelty exposure around a single trail of NOR task in a critical time window on memory consolidation in rats after 24 h and second to determine the expression of BDNF, CREB, c-fos, AChE, MAO, Na+K+-ATPase as potential markers in the medial prefrontal cortex (mPFC) during memory formation. In the present study, to identify and validate the role of these molecular signatures in memory consolidation, infusion of the protein synthesis inhibitor Anisomycin (Ani) was done around the training session that causes a deficit in the formation of LTM when tested 24 h after weak encoding. Altogether, here we are providing the first comprehensive set of evidences indicating that BDNF, CREB, dopamine, some enzymes and c-fos role in modulating LTM by employing behavioural tagging model.

Environment Enrichment Facilitates Long-Term Memory Consolidation through Behavioral Tagging.

The behavioral tagging (BT) hypothesis provides crucial insights into the mechanism of long-term memory (LTM) consolidation. Novelty exposure in BT is a decisive step in activating the molecular machinery of memory formation. Several studies have validated BT using different neurobehavioral tasks; however, the novelty given in all studies is open field (OF) exploration. Environment enrichment (EE) is another key experimental paradigm to explore the fundamentals of brain functioning. Recently, several studies have highlighted the importance of EE in enhancing cognition, LTM, and synaptic plasticity. Hence, in the present study, we investigated the effects of different types of novelty on LTM consolidation and plasticity-related protein (PRP) synthesis using the BT phenomenon. Novel object recognition (NOR) was used as the learning task for rodents (male Wistar rats), while OF and EE were two types of novel experiences provided to the rodents. Our results indicated that EE exposure efficiently leads to LTM consolidation through the BT phenomenon. In addition, EE exposure significantly enhances protein kinase Mζ (PKMζ) synthesis in the hippocampus region of the rat brain. However, the OF exposure did not lead to significant PKMζ expression. Further, our results did not find alterations in BDNF expression after EE and OF exposure in the hippocampus. Hence, it is concluded that different types of novelty mediate the BT phenomenon up to the same extent at the behavioral level. However, the implications of different novelties may differ at molecular levels.

Memory related molecular signatures: The pivots for memory consolidation and Alzheimer's related memory decline.

Age-related cognitive decline is the major cause of concern due to its 70% more incidence than dementia cases worldwide. Moreover, aging is also the major risk factor of Alzheimer's disease (AD), associated with progressive memory loss. Approx. 13 million people will have Alzheimer-related memory decline by 2050. Learning and memory is the fundamental process of brain functions. However, the mechanism for the same is still under investigation. Thus, it is critical to understand the process of memory consolidation in the brain and extrapolate its understanding to the memory decline mechanism. Research on learning and memory has identified several molecular signatures such as Protein kinase M zeta (PKMζ), Calcium/calmodulin-dependent protein kinase II (CaMKII), Brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) and Activity-regulated cytoskeleton-associated protein (Arc) crucial for the maintenance and stabilization of long-term memory in the brain. Interestingly, memory decline in AD has also been linked to the abnormality in expressing these memory-related molecular signatures. Hence, in the present consolidated review, we explored the role of these memory-related molecular signatures in long-term memory consolidation. Additionally, the effect of amyloid-beta toxicity on these molecular signatures is discussed in detail.

Dodging blood brain barrier with "nano" warriors: Novel strategy against ischemic stroke.

Ischemic stroke (IS) is one of the leading causes of death and disability resulting in inevitable burden globally. Ischemic injury initiates cascade of pathological events comprising energy dwindling, failure of ionic gradients, failure of blood brain barrier (BBB), vasogenic edema, calcium over accumulation, excitotoxicity, increased oxidative stress, mitochondrial dysfunction, inflammation and eventually cell death. In spite of such complexity of the disease, the only treatment approved by US Food and Drug Administration (FDA) is tissue plasminogen activator (t-PA). This therapy overcome blood deficiency in the brain along with side effects of reperfusion which are responsible for considerable tissue injury. Therefore, there is urgent need of novel therapeutic perspectives that can protect the integrity of BBB and salvageable brain tissue. Advancement in nanomedicine is empowering new approaches that are potent to improve the understanding and treatment of the IS. Herein, we focus nanomaterial mediated drug delivery systems (DDSs) and their role to bypass and cross BBB especially via intranasal drug delivery. The various nanocarriers used in DDSs are also discussed. In a nut shell, the objective is to provide an overview of use of nanomedicine in the diagnosis and treatment of IS to facilitate the research from benchtop to bedside.

Cross-Talk Between Key Players in Patients with COVID-19 and Ischemic Stroke: A Review on Neurobiological Insight of the Pandemic.

The global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore and examine the possible links between COVID-19 and ischemic stroke (IS). Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. The swift increase in the knowledge of SARS-CoV-2 has given creditable evidence that SARS-CoV-2 infected patients also encounter neurological deficits. As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra. The COVID-19 pandemic has affected people with various pre-existing diseases, including IS, in such a way that these patients need special care and attention for their survival. Several clinical trials are currently ongoing worldwide as well as many other projects are in different stages of conceptualization and planning to facilitate the effective management of stroke patients with COVID-19 infection.

Role of Yoga and Meditation as Complimentary Therapeutic Regime for Stress-Related Neuropsychiatric Disorders: Utilization of Brain Waves Activity as Novel Tool.

During recent decades, stress-related neuropsychiatric disorders such as anxiety, depression, chronic tension headache, and migraine have established their stronghold in the lives of a vast number of people worldwide. In order to address this global phenomenon, intensive studies have been carried out leading to the advancement of drugs like anti-depressants, anxiolytics, and analgesics which although help in combating the symptoms of such disorders but also create long-term side effects. Thus, as an alternative to such clinical practices, various complementary therapies such as yoga and meditation have been proved to be effective in alleviating the causes and symptoms of different neuropsychiatric disorders. The role of altered brain waves in this context has been recognized and needs to be pursued at the highest level. Thus, the current study provides a review focused on describing the effects of yoga and meditation on anxiety and depression as well as exploring brain waves as a tool for assessing the potential of these complementary therapies for such disorders.

Reversal of Schizophrenia-like Symptoms and Cholinergic Alterations by Melatonin.

BACKGROUND: Melatonin is a neurohormone that is linked to the pathogenesis of schizophrenia. The aim of this study was to assess the potential of melatonin in attenuating MK-801 induced schizophrenia-like behavioral and brain neurotoxicity markers. METHODS: Swiss albino mice were assigned into three groups (n = 6). Animals were administered MK-801 (1 mg/kg/mL, i.p.). MK-801 treated animals were supplemented with melatonin (10 mg/kg/1 mL i.p.) 10 min prior to MK-801 injection. The relative degrees of modulation of induced behaviors by melatonin were assessed in the open field, elevated plus maze, grip strength and rota rod. The changes in neurotoxicity enzymes and neuronal activity (c-fos) were demonstrated in this study. RESULTS: MK-801 injection effected normal open-field behaviors, c-fos expression, motor coordination and muscular strength. Melatonin was able to reduce the histological changes in the prefrontal cortex of mice brain. CONCLUSION: Our data demonstrated that the treatment with melatonin attenuates the schizophrenic like symptoms in the mice having a protective effect on prefrontal cortex region of brain by mitigating the alteration of neurotoxicity markers. The protective effect of the treatment was shown to reduced elevation of AChE, c-fos expression and histopathological alterations.