Zul Merali

Zul Merali
Ottawa University · Faculties of Social Sciences and Medicine

About

265
Publications
26,990
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14,154
Citations
Additional affiliations
January 2011 - December 2015
Ottawa University
Position
  • President & CEO Institute of Mantal Health Research

Publications

Publications (265)
Article
The first aim of the present review is to provide an in-depth description of the cannabinoids and their known effects at various neuronal receptors. It reveals that cannabinoids are highly diverse, and recent work has highlighted that their effects on the central nervous system (CNS) are surprisingly more complex than previously recognized. Cannabi...
Article
Full-text available
A novel botanical dietary supplement, formulated as a chewable tablet containing a defined mixture of Souroubea spp. vine and Platanus spp. Bark, was tested as a canine anxiolytic for thunderstorm noise-induced stress (noise aversion). The tablet contained five highly stable triterpenes and delivered 10 mg of the active ingredient betulinic acid (B...
Article
Full-text available
Background: Souroubea sympetala Gilg. is a neotropical vine native to Central America, investigated as part of a targeted study of the plant family Marcgraviaceae. Our previous research showed that extract of S. sympetala leaf and small branch extract had anxiolytic effects in animals and acts as an agonist for the GABAA receptor at the benzodiazep...
Article
Full-text available
Background: Δ9-Tetrahydrocannabinol (THC, a CB1 receptor agonist) and Cannabidiol (CBD, a non-competitive antagonist of endogenous CB1 and CB2 ligands) are two primary components of Cannabis species, and may modulate fear learning in mammals. The CB1 receptor is widely distributed throughout the cortex and some limbic regions typically associated w...
Article
Full-text available
Background: Δ9-Tetrahydrocannabinol (THC, a CB1 receptor agonist) and Cannabidiol (CBD, a non-competitive antagonist of endogenous CB1 and CB2 ligands) are two primary components of Cannabis species, and may modulate fear learning in mammals. The CB1 receptor is widely distributed throughout the cortex and some limbic regions typically associated w...
Article
Full-text available
Background: Abnormalities in heart rate during sleep linked to impaired neuro-cardiac modulation may provide new information about physiological sleep signatures of depression. This study assessed the validity of an algorithm using patterns of heart rate changes during sleep to discriminate between individuals with depression and healthy controls....
Article
Full-text available
Context: Depressive symptoms are highly prevalent and cause substantive morbidities and loss of functioning among employees. Depression may be prevented at its early stages. However, there is a paucity of information regarding indicated preventive interventions for depression among employees. The objective of this review is to examine the effectiv...
Article
Full-text available
Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are first-line antidepressants but require several weeks to elicit their actions. Chronic SSRI treatment induces desensitization of 5-HT1A autoreceptors to enhance 5-HT neurotransmission. Mice (both sexes) with gene deletion of 5-HT1A autoreceptors in adult 5-HT neurons (1AcKO) were tested for...
Article
Full-text available
The juvenile period is marked by a reorganization and growth of important brain regions including structures associating with reward seeking behaviors such as the nucleus accumbens (NA) and prefrontal cortex (PFC). These changes are impacted by stressors during the juvenile period and may lead to a predisposition to stress induced psychopathology a...
Article
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The 5-HT1A autoreceptor mediates feedback inhibition of serotonin (5-HT) neurons, and is implicated in major depression. The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription. Since chronic stress alters HTR1A methylation and expression, we addressed whether recrui...
Article
Ethnopharmacological relevance: The Maya have traditionally used copal, Protium copal, as incense during ceremonies since pre-Columbian times. Anecdotally, copal (when burned as incense), is thought to elicit mentally uplifting and calming effects. The main objective of this study was to determine whether the incense elicits anxiolytic-like behavi...
Article
Background: Gastrin Releasing Peptide (GRP) may play a role in fear learning. The GRP Receptor is expressed in the basolateral amygdala and hippocampus, and central administration of GRP mediates fear learning. The effects of GRP on reconsolidation, however, have been minimally explored. Reconsolidation, the process by which formed memories are re...
Article
Full-text available
Freud-1/CC2D1A represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo, we generated mice with adulthood conditional knockout of Freud-1 in 5-HT neurons (cF1ko). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with...
Article
Full-text available
As part of our ongoing research into botanical therapies for anxiety disorders, the neotropical vine Souroubea sympetala was chosen for study as a phytochemical discovery strategy focusing on rare Central American plant families. When orally administered to male Sprague-Dawley rats, the crude plant extract, its ethyl acetate fraction, supercritical...
Article
Appreciable evidence suggests that perturbations within the gut microbiome and the immune system may play a key role in the pathogenesis of depression stemming from earlier stressful experiences. In the present investigation we examined whether microbial changes in cecum contents were associated with social avoidance behaviors, a feature of depress...
Article
In adult rats, access to a palatable diet can buffer against the effects of stressors. Approximately 10% of all adolescents are repeatedly victimized by their peers raising the possibility that palatable food consumption may be relevant to this developmental window. This study assessed the long-term impact of juvenile social defeat exposure on anxi...
Article
Rhodiola rosea is a plant with adaptogenic qualities used by Inuit populations of Nunavik, Quebec (Canada) for general mental and physical rejuvenation. Previous studies have demonstrated that the Canadian populations of R. rosea significantly attenuate the expression of learned fear and anxiety-like behaviors in rodent models. In order to further...
Article
Background: Major depression is a prevalent mental disorder and imposes considerable burden on health and productivity. Men are not immune to major depression, yet they often delay seeking help because of perceived stigma and gender norms. E-mental health programs hold potential for early prevention of major depression. However, we have little kno...
Article
One in 3 of us will experience mental illness in our lifetime, and yet the current treatments as well as the development of new strategies haven’t been overly encouraging.1 In economically developed countries mental illness exerts an enormous social and economic toll; in Canada, for instance, more than 500 000 people will not go to work daily owing...
Article
Full-text available
Cognitive behavioral group therapy (CBGT) has been reported to be more effective than a mindfulness-based stress reduction program (MBSR) in reducing symptoms of social anxiety disorder (SAD). The present study determined whether CBGT and MBSR differentially affected subjective anxiety and physiological response to a stressful speaking task. The sa...
Article
Ethnopharmacological relevance: The medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q'eqchi' Maya healers for the treatment of "susto,"a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago...
Article
The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial...
Article
Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem sa...
Article
Full-text available
Objectives: The polyphenol resveratrol has shown regulatory effects on hippocampal neurogenesis, which according to the neurovascular niche hypothesis, is likely to involve stimulation of angiogenesis. In rodents, global cerebral ischemia leads to selective CA1 neuronal damage, spatial memory impairments, lasting changes in corticosterone (CORT) s...
Article
Full-text available
Stressful events have been implicated in the evolution of mood disorders. In addition to brain neurotransmitters and growth factors, the view has been offered that these disorders might be provoked by the activation of the inflammatory immune system as well as by de novo changes of inflammatory cytokines within the brain. The present review describ...
Conference Paper
Full-text available
The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by recent times of civil unrest and war throughout the world. Many of the currently prescribed drug therapies for anxiety disorders are associated with aversive side-effects and lose efficacy with repeated administration. Ethnobotanical research has shown tha...
Article
Full-text available
Social relationships are tightly linked to health and well-being. Recent work suggests that social relationships can even serve vital emotion regulation functions by minimizing threat-related neural activity. But relationship distress remains a significant public health problem in North America and elsewhere. A promising approach to helping couples...
Article
The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important GABAA-benzodiazepine (GABAA-BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 m...
Article
Background: Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of dep...
Article
Full-text available
Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety...
Conference Paper
Full-text available
The prevalence of anxiety disorders is rising rapidly in today’s society, impacted greatly by recent times of civil unrest and war throughout the world. Many of the currently prescribed drug therapies for anxiety disorders are associated with aversive side-effects and lose efficacy with repeated administration. Ethtnobotanical research has shown th...
Article
The neotropical lianas Souroubea gilgii and Souroubea sympetala (Marcgraviaceae) were chosen for study as part of a phytochemical discovery strategy focusing on rare plant families in Central America. In participatory research, Q’eqchi’ healers in Belize reported the use of these plants to reverse psychological symptoms inflicted by witchcraft. Ext...
Article
Gastrin releasing peptide, the mammalian counterpart of the amphibian peptide, Bombesin, has been increasingly implicated in regulating normal brain function as well as in the pathogenesis of psychiatric and/or neurodevelopmental disorders. We have previously shown that the neonatal blockade of the gastrin-releasing peptide receptor (GRPr) in rats...
Article
Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signals regulation 30 days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH)...
Article
Full-text available
Social relationships are tightly linked to health and well-being. Recent work suggests that social relationships can even serve vital emotion regulation functions by minimizing threat-related neural activity. But relationship distress remains a significant public health problem in North America and elsewhere. A promising approach to helping couples...
Chapter
This chapter focuses on some of the methods currently available to study neural?immune interactions. Specifically, it considers methods that allow us to assess how an immune challenge may come to influence the neurochemistry of the brain and how nerve cell activity is modified by immune system signaling. This description will, hopefully, serve as a...
Article
Full-text available
The current obesity "epidemic" in the developed world is a major health concern; over half of adult Canadians are now classified as overweight or obese. Although the reasons for high obesity rates remain unknown, an important factor appears to be the role stressors play in overconsumption of food and weight gain. In this context, increased stressor...
Article
Neuropeptides act as signaling molecules that regulate a range of aspects of brain function. Gastrin-releasing peptide (GRP) is a 27-amino acid mammalian neuropeptide, homolog of the amphibian peptide bombesin. GRP acts by binding to the GRP receptor (GRPR, also called BB2), a member of the G-protein coupled receptor (GPCR) superfamily. GRP produce...
Article
Rhodiola rosea is a medicinal plant used by the indigenous Inuit people of Nunavik and Nunatsiavut, Eastern Canada, as a mental and physical rejuvenating agent. This traditional use led to the present investigation of R. rosea in the context of anxiety disorders. An alcohol extract of R. rosea roots was characterized phytochemically and orally admi...
Conference Paper
Full-text available
Ketamine, a non-competitive NMDA receptor antagonist, has historically been used as a sedative in veterinary and human medicine. Recent reports suggest that ketamine displays anti-depressant and anxiolytic effects at sub-anaesthetic doses. Other NMDA receptor antagonists disrupt fear memory, however little work has been done on Ketamine in this re...
Article
The basolateral amygdala and infralimbic cortex share strong reciprocal interconnections and are key structures in conditioned fear circuitry. Gastrin-releasing peptide (GRP) or its receptor antagonists can modulate the conditioned fear response when exogenously administered at either of these sites, and increased release of GRP at the basolateral...
Article
Full-text available
Molecular mechanisms behind the etiology and pathophysiology of major depressive disorder and suicide remain largely unknown. Recent molecular studies of expression of serotonin, GABA and CRH receptors in various brain regions have demonstrated that molecular factors may contribute to the development of depressive disorder and suicide behaviour. He...
Data
GO Analysis of Differentially Expressed Gene List (p<0.01 FC >1.3). (DOCX)
Data
GO analysis of DEGS from pathway analysis (largest network). (DOCX)
Data
GO analysis of genes correlated in suicide group. (DOCX)
Article
Abstract Mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) act by activating NMB receptors (NMBR, BB1) and GRP receptors (GRPR, BB2), respectively. These two bombesin receptors are members of the G-protein-coupled receptor (GPCR) superfamily. In the brain, NMBR and GRPR are highly expressed in the brain areas i...
Chapter
GABA and GABAA receptors are ubiquitous within the central nervous systems, playing a fundamental role in controlling neural inhibition and timing of neural networks (i.e., gating pyramidal cell synchrony) (Traub et al., 1999; Whitington and Traub, 2003; Whittington et al., 1995). GABAA receptors are pentameric protein complexes constructed from pr...
Article
Background: Serum brain-derived neurotrophic factor (BDNF) protein has been related to depression and less consistently to its treatments in human studies. However, animal studies have failed to demonstrate a clear link between BDNF protein in serum and brain tissue. Methods: Serum and brain tissue levels of BDNF protein were measured with ELISA...
Article
Full-text available
In many rodent laboratories, blood samples are collected from rats using the tail vein nick procedure and analyzed to quantify blood corticosterone levels as an indicator of stress. The standard method of corticosterone quantification often requires the collection of a relatively large volume of blood, followed by the extraction of the blood plasma...
Article
Several lines of evidence have implicated bombesin and its mammalian analogue, gastrin-releasing peptide (GRP), in the mediation and/or modulation of the stress response. However, the physiological role of GRP in mediating conditioned fear responses remains to be elucidated. The objective of the present study was to characterize the role(s) of GRP...
Article
Given the modulatory effect of exogenously administered corticotropin-releasing hormone (CRH) and gastrin-releasing peptide (GRP) on conditioned fear, the present study sought to measure the fear-induced endogenous release of CRH and GRP at the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) using in vivo microdialysis. Rats were div...
Article
The purpose of this work was to develop an extraction technique to yield a betulinic acid-(BA) enriched extract of the traditional anti-anxiety plant Souroubea sympetala Gilg (Marcgraviaceae). Five extraction techniques were compared: supercritical carbon dioxide extraction (SCE), conventional solvent extraction with ethyl acetate (EtOAc), accelera...
Article
Full-text available
Inter-relationships ordinarily exist between mRNA expression of GABA(A) subunits in the frontopolar cortex (FPC) of individuals that had died suddenly from causes other than suicide. However, these correlations were largely absent in persons that had died by suicide. In the present investigation, these findings were extended by examining GABA(A) re...
Article
GABA(A) functioning has been implicated in anxiety and depressive disorders. In this regard, we suggested that in addition to analyzing GABA(A) and the subunits that comprise the GABA(A) receptor, it might be profitable to assess the coordinated expression of subunits that comprise the GABA(A) receptor cassette. We demonstrate that certain subunits...
Chapter
Exposure to inescapable shock provokes behavioral disturbances in subsequent shock-escape tests, as well as in other behavioral paradigms, including those that reflect anhedonia. The interference induced by inescapable shock using a yoked (triadic) paradigm has frequently been referred to as a “learned helplessness” paradigm. The interference effec...
Article
The Q'eqchi' Maya possess a large selection of plants to treat neurological disorders, including epilepsy and susto (fright), a culture-bound illness related to anxiety disorders. To investigate the activity of antiepileptic and anxiolytic plants in the GABAergic system, and determine if there is a pharmacological basis for plant selection. Ethanol...
Article
Repeated exposure to stressors was reported to increase the expression of arginine-vasopressin (AVP), especially in corticotropin-releasing hormone (CRH) neurons co-expressing AVP, within the hypothalamus. This may increase the potential for subsequent stressor-elicited enhancement of hypothalamic-pituitary-adrenal (HPA) functioning as these peptid...
Article
Full-text available
Epigenetic mechanisms may be involved in the reprogramming of gene expression in response to stressful stimuli. This investigation determined whether epigenetic phenomena might similarly be associated with suicide/depression. The expression of DNA methyltransferase (DNMT) mRNA was assessed in several brain regions of individuals who had committed s...