Amal Chandra Mondal

Decreased mRNA and Protein Expression of BDNF, NGF, and their Receptors in the Hippocampus from Suicide: An Analysis in Human Postmortem Brain

Despite the devastating effect of suicide on numerous lives, there is still a lack of knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors TrkB and TrkA respectively. The present study was performed to examine whether the expression profiles of BDNF and/or TrkB as well as NGF and/or TrkA were altered in the hippocampus of postmortem brain of the participants, who had committed suicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed on the hippocampus of 21 suicide victims and 19 non-psychiatric control individuals. The protein and mRNA levels of BDNF, TrkB, NGF, and TrkA were determined by sandwich enzyme-linked immunosorbent assay, Western blot and reverse transcription-PCR. Given the importance of BDNF and NGF and their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, TrkB, NGF, and TrkA on both the protein and mRNA levels of postmortem brains of suicide victims suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.

Chronic administration of bacopa monniera increases BDNF protein and mRNA expressions: a study in chronic unpredictable stress induced animal model of depression.

Objective The present study aimed to investigate whether graded doses of Bacopa Monniera (BM) extract could produce antidepressant-like effects in chronic unpredictable stress (CUS) induced depression in rats and its possible mechanism(s). Methods Rats were subjected to an experimental setting of CUS. The effect of BM extract treatment in CUS-induced depression was examined using behavioral tests including the sucrose consumption, open field test and shuttle box escape test. The mechanism underlying the antidepressant-like action of BM extract was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats. Results Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity and escape latency. In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex. Conclusion The results suggest that BM extract alleviates depression induced by CUS. Present study also confirms that 80-120 mg/kg doses of BM extract have significantly higher antidepressant-like activity.

Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri

Objective The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. Methods We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). Results Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. Conclusion These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior.

Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat.

Major depression is a life threatening neuropsychiatric disorder that produces mental illness and major cause of morbidity. The present study was conducted to evaluate the neuroprotective, neurotrophic and antioxidant potential of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced behavioral depression in rats. Behavioral tests were carried out for investigation of antidepressant like effects of BME, and potential mechanism was assessed by determining neurotrophin level and hippocampal neurogenesis. Depressive-like behavior was assessed by shuttle-box escape test, forced swim test and tail suspension test. Effect of BME on hypothalamic–pituitary–adrenal (HPA) axis was evaluated by measuring the plasma level of adrenocorticotropic hormone (ACTH) and corticosterone. The expression of brain derived neurotrophic factor (BDNF), neuronal marker doublecortin (DCX) in the hippocampus were measured and hippocampal neurogenesis was investigated by 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). In addition, effects of BME on oxidative stress markers were also measured in the hippocampus of CUS exposed rats. The results indicated that BME significantly able to attenuate the depressive-like behaviors, normalized the levels of ACTH, corticosterone, and up-regulate the expression of BDNF, DCX and BrdU/NeuN in CUS induced rats compared to BME treated rats. It is also found that BME significantly increased the activity of antioxidant enzymes on CUS induced rats. These findings revealed that BME exerted neuroprotective effects possibly by promoting hippocampal neurogenesis with elevation of BDNF level and antioxidant defense against oxidative stress.

Prenatal stress and depression associated neuronal development in neonates

Prenatal maternal depression has its direct effects on early brain development deficits with permanent changes in neuroendocrine functions and impaired behavior in offsprings. Prenatal stress (PS) transmits its affect on developing fetus and on pregnancy outcomes in adult offsprings. This results in impaired neurodevelopment, delayed cognitive and motor development with impaired behavior towards stressful conditions. There are sufficient evidences in animal models suggesting depression responsive hypothalamic‐pituitary‐adrenal (HPA) axis and its hormonal response via cortisol, responsible for its critical effects in both the mother and offspring. We review the evidences how maternal psychological distress has widespread effect on fetal/birth outcomes via major physiological alteration in HPA axis, autonomic nervous system, neurotransmitters and signaling pathways. Knowledge void in the area of epigenetic processes like DNA methylation, histone acetylation and regulation of microRNA during prenatally stressed fetal neurodevelopment has to be filled up with properly defined controls. This aims the need to reexamine available literatures and to explore more directional approaches for prevention of PS as well as future treatment for the well being of the mother and fetus during critical physiological changes.

Cellular and Molecular attributes of Neural Stem Cell Niches in Adult Zebrafish Brain

Adult neurogenesis is a complex, presumably conserved phenomenon in vertebrates with a broad range of variations regarding neural progenitor/stem cell niches, cellular composition of these niches, migratory patterns of progenitors and so forth among different species. Current understanding of the reasons underlying the inter‐species differences in adult neurogenic potential, the identification and characterization of various neural progenitors, characterization of the permissive environment of neural stem cell niches and other important aspects of adult neurogenesis is insufficient. In the last decade, zebrafish has emerged as a very useful model for addressing these questions. In this review, we have discussed the present knowledge regarding the neural stem cell niches in adult zebrafish brain as well as their cellular and molecular attributes. We have also highlighted their similarities and differences with other vertebrate species. In the end, we shed light on some of the known intrinsic and extrinsic factors that are assumed to regulate the neurogenic process in adult zebrafish brain.

Important medicinal herbs in Parkinson’s disease pharmacotherapy

Parkinsons disease (PD) is the most common progressive neurodegenerative movement disorder affecting more than 10 million people worldwide. The characteristic hallmark of PD involves progressive loss of dopaminergic (DA-ergic) neuron in Substantia Nigra pars compacta (SNpc) region of the brain, however, aetiology of the disease still remains unclear. Mitochondrial dysfunction and oxidative insult are considered to be the key culprit. The current therapy available for PD primarily relies on Levodopa that offers the potential of slowing down disease progression to some extent but includes lot of side effects. Any potential drug capable of treating or halting the disease still remains to be identified. It is evident that redox stabilization and replenishment of mitochondrial function seem to be an important therapeutic approach against PD as both are required for optimal neuronal functioning. Enormous research done in this field has shown that some natural and synthetic products exhibit neuroprotective and anti-apoptotic potential by improving mitochondrial function and alleviating oxidative stress. Therefore, the present review aims to discuss some of the important medicinal natural herbs (Bacopa monnieri, Mucuna pruriens, Withania somnifera, Curcuma longa, Gingko Biloba, and Camellia sinensis) in context to their neuroprotective potential and also in the development of novel therapeutic strategies against PD.

TrkB receptor antagonism inhibits stab injury induced proliferative response in adult zebrafish (Danio rerio) brain

The Tropomyosin related kinase B (TrkB) receptor, is known to promote neuronal maturation, differentiation, maintenance and survival through its cognate ligands Brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4). BDNF, NT4 and TrkB are highly conserved proteins among vertebrates. Although the role of TrkB during brain development is well established, its role in adult neurogenesis and brain regeneration awaits thorough investigation. In this study, we used the zebrafish stab wound injury model to determine whether the injury induced regeneration response in the telencephalon region is governed by TrkB or not. We induced stab wound injury in the mid-dorsal region of telencephalon of ANA-12 (selective TrkB antagonist) treated and non-treated zebrafish brain and examined the proliferation activity in selected brain regions using immunohistochemistry. We found that proliferation activity was significantly low in ANA-12 injected injured fishes as compared to vehicle control injured fishes. Other major findings of the study include the temporal pattern of proliferation activity after an injury and activation of adult neural stem cells (aNSCs) situated distantly apart from the injury site in the adult zebrafish brain.

Evaluation of naproxen-induced oxidative stress, hepatotoxicity and in-vivo genotoxicity in male Wistar rats

Naproxen (NP), a nonsteroidal anti-inflammatory drug (NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP; therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP. Male Wistar rats were administered NP orally at the doses of 38.91 and 65.78 mg/kg body weight for 14 days. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) activities/levels were measured in the liver, kidney and brain tissues. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and total bilirubin (TBIL) levels were measured in the liver tissues. Micronucleus frequency (micronucleus test MNT) and DNA damage (comet assay) were performed in the bone marrow cells and leukocytes, respectively. The results showed that NP treatment decreased the GSH levels and increased the SOD, CAT, LPO, ALT, AST, ALP and TBIL activities/levels compared to the control (p < 0.05). Results of MNT showed an increased micronucleus induction and comet assay showed a significant increase in DNA damage in the NP treated animals (p < 0.05). Treatment of NP resulted in the biochemical imbalance and induced oxidative stress that deteriorated the integrity of the cells, which caused significant damage to the genetic material and affected liver function in male Wistar rats. Therefore, NP is a potential genotoxic agent that induces genotoxicity and oxidative stress.

Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro.

Alzheimers disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid‐β oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid‐β (Aβ). Increased production of Aβ invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. This study was aimed to investigate the neuroprotective effects of a β‐sheet breaker α/β‐hybrid peptide (BSBHp) and the underlying mechanisms against Aβ40‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells. Cells were pretreated with the peptide Aβ40 to induce neurotoxicity. Assays for cell viability, cell membrane damage, cellular apoptosis, generation of reactive oxygen species (ROS), intracellular free Ca2+, and key apoptotic protein levels were performed in vitro. Our results showed that pretreatment with BSBHp significantly attenuates Aβ40‐induced toxicity by retaining cell viability, suppressing generation of ROS, Ca2+ levels, and effectively protects neuronal apoptosis by suppressing pro‐apoptotic protein Bax and up‐regulating antiapoptotic protein Bcl‐2. These results suggest that α/β‐hybrid peptide has neuroprotective effects against Aβ40‐induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.